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1. Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses

Author

University of Michigan ICPCG Group ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, University of Michigan ICPCG Group ; University of Michigan, Ann Arbor, Michigan, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah ; Division of Genetic Epidemiology, University of Utah School of Medicine, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108., African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania, African American Hereditary Prostate Cancer ICPCG Group ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, African American Hereditary Prostate Cancer ICPCG Group ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, Arizona, ACTANE Consortium ICPCG Group ; Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Department of Oncology, McGill University, Montreal, Quebec, Canada, ACTANE Consortium ICPCG Group ; The Norwegian Radium Hospital, Oslo, Norway, ACTANE Consortium ICPCG Group ; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey, UK, ACTANE Consortium ICPCG Group ; Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK, ACTANE Consortium ICPCG Group ; Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington, BC/CA/HI ICPCG Group ; Department of Health Research and Policy, Stanford School of Medicine, Stanford, California ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, FHCRC ICPCG Group ; Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, Washington, FHCRC ICPCG Group ; Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland, FHCRC ICPCG Group ; Institute for Systems Biology, Seattle, Washington, Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, Mayo Clinic ICPCG Group and Mayo Clinic, Rochester, Minnesota, University of Tampere ICPCG Group, University of Tampere and Tampere University Hospital, Tampere, Finland, University of Ulm ICPCG Group ; Department of Urology, University of Ulm, Ulm, Germany, University of Ulm ICPCG Group ; Institute of Human Genetics, University of Ulm, Ulm, Germany, University of Ume?? ICPCG Group ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, University of Ume?? ICPCG Group ; Oncologic Centre, Ume?? University, Ume??, Sweden, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, Christensen, G. Bryce, Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L. J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Gr??nberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M., Cannon-Albright, Lisa A., Camp, Nicola J., University of Michigan ICPCG Group ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, University of Michigan ICPCG Group ; University of Michigan, Ann Arbor, Michigan, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah ; Division of Genetic Epidemiology, University of Utah School of Medicine, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108., African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania, African American Hereditary Prostate Cancer ICPCG Group ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, African American Hereditary Prostate Cancer ICPCG Group ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, Arizona, ACTANE Consortium ICPCG Group ; Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Department of Oncology, McGill University, Montreal, Quebec, Canada, ACTANE Consortium ICPCG Group ; The Norwegian Radium Hospital, Oslo, Norway, ACTANE Consortium ICPCG Group ; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey, UK, ACTANE Consortium ICPCG Group ; Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK, ACTANE Consortium ICPCG Group ; Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington, BC/CA/HI ICPCG Group ; Department of Health Research and Policy, Stanford School of Medicine, Stanford, California ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, FHCRC ICPCG Group ; Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, Washington, FHCRC ICPCG Group ; Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland, FHCRC ICPCG Group ; Institute for Systems Biology, Seattle, Washington, Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, Mayo Clinic ICPCG Group and Mayo Clinic, Rochester, Minnesota, University of Tampere ICPCG Group, University of Tampere and Tampere University Hospital, Tampere, Finland, University of Ulm ICPCG Group ; Department of Urology, University of Ulm, Ulm, Germany, University of Ulm ICPCG Group ; Institute of Human Genetics, University of Ulm, Ulm, Germany, University of Ume?? ICPCG Group ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, University of Ume?? ICPCG Group ; Oncologic Centre, Ume?? University, Ume??, Sweden, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, Christensen, G. Bryce, Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L. J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Gr??nberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M., Cannon-Albright, Lisa A., and Camp, Nicola J.

Abstract

BACKGROUND Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11???q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9???cM. CONCLUSIONS Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate 70: 735???744, 2010. ?? 2010 Wiley-Liss, Inc.

Published
2010

2. Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk

Author

Cyrille Cuenin, Salvatore Panico, Rosario Tumino, Anthony J. Swerdlow, Domenico Palli, Pierre Antoine Dugué, Nick Orr, Sara Grioni, Michael Jones, Francesca Fasanelli, Isabelle Romieu, Silvia Polidoro, Vittorio Perduca, Srikant Ambatipudi, Melissa C. Southey, Minouk J. Schoemaker, Olivia Fletcher, Graham G. Giles, Paolo Vineis, Maria Concetta Giurdanella, Giovanna Masala, James M. Flanagan, Annelie Johansson, Amalia Mattiello, Nichola Johnson, Dallas R. English, Gianluca Severi, Katarzyna Tomczyk, Roger L. Milne, Carlotta Sacerdote, Claudia Agnoli, Laura Baglietto, Veronique Chajes, Zdenko Herceg, Breast Cancer Now, Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Tuscany, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Epidemiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Cancer Registry, Center for Cancer Prevention, CPO-Piemonte, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Human Genetics Foundation (HuGeF), Torino, Italy., The institute of cancer research [London], Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Australia, parent, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne, Cancer Epidemiology Centre, Cancer Council Victoria, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), International Agency for Cancer Research (IACR), Epidemiology section, Institute of Cancer Research in Sutton, University of Torino and CPO-Piemonte, Università degli studi di Torino (UNITO), Perduca, Vittorio, University of Naples Federico II = Università degli studi di Napoli Federico II, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Università degli studi di Torino = University of Turin (UNITO)

Subjects
BIOMARKER, 0301 basic medicine, Oncology, Bisulfite sequencing, Epigenesis, Genetic, Cancer risk, REANALYSIS, Breast cancer, 0302 clinical medicine, [STAT.AP] Statistics [stat]/Applications [stat.AP], Prospective Studies, skin and connective tissue diseases, Prospective cohort study, Genetics (clinical), Genetics & Heredity, [STAT.AP]Statistics [stat]/Applications [stat.AP], OUTCOMES, DNA methylation, WOMEN, Middle Aged, Biomarker, Epigenetics, Estrogen exposure, EWAS, Hormonal exposures, 3. Good health, Italy, CpG site, 030220 oncology & carcinogenesis, Female, Life Sciences & Biomedicine, medicine.medical_specialty, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, PERIPHERAL-BLOOD, 03 medical and health sciences, AGE, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Internal medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, Molecular Biology, METAANALYSIS, Science & Technology, business.industry, Research, Case-control study, Cancer, Estrogens, medicine.disease, BODY-MASS INDEX, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, CpG Islands, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SEX-HORMONES, business, Genome-Wide Association Study, Developmental Biology
Abstract

Background It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman’s total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. Methods An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs. Results We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04–1.07, P = 3 × 10−12) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q

Published
2019
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3. Alcohol consumption is associated with widespread changes in blood DNA methylation: Analysis of cross-sectional and longitudinal data

Author

Daniel F. Schmidt, Rory P. Wilson, Melanie Waldenberger, Laura Baglietto, Harindra Jayasekara, Benjamin Lehne, Graham G. Giles, Pierre Antoine Dugué, Jaspal S. Kooner, Melissa C. Southey, Xiaochuan Wang, Annette Peters, Karl-Heinz Ladwig, Dallas R. English, John C Chambers, Jihoon E. Joo, Christian Gieger, Roger L. Milne, Chol-Hee Jung, Gianluca Severi, Enes Makalic, Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], University of Melbourne-Melbourne School for Population and Global Health, Melbourne School of Population and Global Health [Melbourne], University of Melbourne, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, London, W2 1PG, Melbourne Bioinformatics [Australia], The University of MelbourneParkville, VIC, Australia., Department of Clinical and Experimental Medicine, University of Pisa, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), München, Technische Universität München, German Research Center for Cardiovascular Disease (DZHK), Partner site Munich Heart Alliance, Institute of Epidemiology and Medical Biometry, University of Ulm, Munich, Germany, Ealing Hospital, Imperial College Healthcare NHS Trust, Monash University [Clayton], Nanyang Technological University [Singapour], Imperial College Healthcare NHS Trust Oregon Department of Agriculture, ODA: 16/136/68 279143 Wellcome Trust, WT: 084723/Z/08/Z, 090532, RP‐PG‐0407‐10371, 098381 Cancer Council Victoria: 1026892, 1027505, 251553, 209057, 1050198, 1011618, 1074383, 504711, 1043616 Bundesministerium für Bildung und Forschung, BMBF VicHealth British Heart Foundation, BHF: SP/04/002 Münchner Zentrum für Gesundheitswissenschaften, Ludwig-Maximilians-Universität München National Institute for Health Research, NIHR National Health and Medical Research Council, NHMRC: 1088405 Horizon 2020 Framework Programme, H2020: 643774 ERAB: The European Foundation for Alcohol Research, ERAB: ERAB 2018 – EA1817 Medical Research Council, MRC: G0601966, G0700931 National Medical Research Council, NMRC: NMRC/STaR/0028/2017, and This work (MCCS) was supported by the Australian National Health and Medical Research Council (NHMRC) (Grant 1088405). MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC Grants 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. Cases were ascertained through the Victorian Cancer Registry (VCR) and the Australian Cancer Database (Australian Institute of Health and Welfare). The nested case‐control methylation studies were supported by the NHMRC Grants 1011618, 1026892, 1027505, 1050198, 1043616, and 1074383. M.C.S. is an NHMRC Senior Research Fellow (1061177). The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research has been supported within the Munich Center of Health Sciences (MC‐Health), Ludwig‐Maximilians‐Universität, as part of LMUinnovativ. This work has received funding from the European Foundation for Alcohol Research (ERAB 2018 – EA1817). We thank all members of field staffs who were involved in the planning and conduct of the MONICA/KORA Augsburg studies. The LOLIPOP study is supported by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust, the British Heart Foundation (SP/04/002), the Medical Research Council (G0601966, G0700931), the Wellcome Trust (084723/Z/08/Z, 090532, and 098381), the NIHR (RP‐PG‐0407‐10371), the NIHR Official Development Assistance (ODA, award 16/136/68), the European Union FP7 (EpiMigrant, 279143), and H2020 programs (iHealth‐T2D, 643774). We acknowledge support of the MRC‐PHE Centre for Environment and Health and the NIHR Health Protection Research Unit on Health Impact of Environmental Hazards. The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the Imperial College Healthcare NHS Trust, the NHS, the NIHR, or the Department of Health. We thank the participants and research staff who made the study possible. JC is supported by the Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research Investigator (STaR) Award (NMRC/STaR/0028/2017).

Subjects
Male, longitudinal data, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Physiology, Alcohol, Disease, Epigenesis, Genetic, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Prospective Studies, education.field_of_study, 0303 health sciences, DNA methylation, Confounding, Regression analysis, Methylation, Middle Aged, epigenome-wide association study, Substance abuse, Psychiatry and Mental health, 030220 oncology & carcinogenesis, Female, Alcohol consumption, Cohort study, Adult, Alcohol Drinking, Longitudinal data, alcohol consumption, Population, 03 medical and health sciences, Genetic, cross-sectional data, EWAS, HM450 assay, Aged, CpG Islands, Cross-Sectional Studies, Genome-Wide Association Study, Humans, DNA Methylation, Epigenetics, education, 030304 developmental biology, Pharmacology, business.industry, Alcohol Consumption, Cross-sectional Data, Dna Methylation, Epigenome-wide Association Study, Ewas, Hm450 Assay, Longitudinal Data, medicine.disease, 030227 psychiatry, chemistry, business, 030217 neurology & neurosurgery, Epigenesis
Abstract

Background:DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart.Methods:Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined using baseline peripheral blood samples from 5,606 adult Melbourne Collaborative Cohort Study (MCCS) participants. For a subset of 1,088 of them, these measures were repeated using blood samples collected at follow-up, a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. Independent data from the LOLIPOP (N=4,042) and KORA (N=1,662) cohorts were used to replicate associations discovered in the MCCS.Results:Cross-sectional analyses identified 1,414 CpGs associated with alcohol intake at P-7, 1,243 of which had not been reported previously. Of these 1,243 novel associations, 1,078 were replicated (PConclusion:Our study indicates that, for middle-aged and older adults, alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with changes in alcohol consumption.

Published
2021
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4. Research on environmental exposure to noise and risk of cardiometabolic diseases (type 2 diabetes, hypertension, cardiovascular diseases) through devices connected to the E3N-E4N cohort in Ile-de-France and Auvergne Rhône-Alpes (2000-2018) - France

Author

Faure, Elodie, Evrard, Anne-Sophie, Vincent, Bruno, Mietlicki, Fanny, Fagherazzi, Guy, Severi, Gianluca, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Institut de recherche sur la biologie de l'insecte UMR7261 (IRBI), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Bruitparif, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Luxembourg Institute of Health (LIH), Cancer Epidemiology Centre, Cancer Council Victoria, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)

Subjects
[PHYS.MECA.VIBR]Physics [physics]/Mechanics [physics]/Vibrations [physics.class-ph], E-Heatlh device, EPIDEMIOLOGY, 3. Good health, NOISE, CARDIO-METABOLIC DISEASES, [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph]
Abstract

International audience; The World Health Organization's (WHO) guidelines for environmental noise (2018) outline the evidence on the health effects of transport noise. The main associated effects are annoyance, sleep disturbance or cardiovascular diseases (CVD). We are currently implementing a project called "BROUHAHA", which will aim to study the association between exposure to transport noise and the risk of cardiometabolic diseases: type 2 diabetes, hypertension or CVD. Component A will be conducted with 35,000 women from the E3N cohort (www.e3n.fr) who resided in Ile-de-France (IdF) or Auvergne Rhône-Alpes (AuRA) (2000-2018). The second component B will be a pilot study conducted with 240 subjects from the E4N (www.e4n.fr) cohort residing in IdF or AuRA. The objective will be to study the effects of short-term noise exposure on heart rate, sleep parameters, hypertension and glycemia. Acoustic and physiological parameters will be measured via an e-health device. This multidisciplinary project is in accordance with WHO recommendations and with the 2002/49/EC Directive on the assessment and management of environmental noise. BROUHAHA will make it possible to complete scientific knowledge on health-related exposure to transport noise and to adapt public health policies in this field.

Published
2020
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5. Discovery of common and rare genetic risk variants for colorectal cancer

Author

Charles M. Connolly, Deborah A. Nickerson, Jian Gong, Sébastien Küry, Barbara Pardini, Brent W. Zanke, Andrea Gsur, Jochen Hampe, Coral Arnau-Collell, M. Henar Alonso, Elio Riboli, Annika Lindblom, Ulrike Peters, Gad Rennert, Tabitha A. Harrison, Lori C. Sakoda, Caroline McNeil, Flavio Lejbkowicz, Hyun Min Kang, David J. Hunter, Martha L. Slattery, Miguel Rodríguez-Barranco, Christina Bamia, Satu Männistö, Timothy J. Key, W. James Gauderman, Gonçalo R. Abecasis, Sanford D. Markowitz, Laurence N. Kolonel, Mark A. Jenkins, Yi Lin, Robin Myte, Hedy S. Rennert, Neil Murphy, Antonia Trichopoulou, Christopher I. Li, Ross L. Prentice, Sai Chen, Stephanie J. Weinstein, Kristin E. Anderson, Hua Ling, Mitul Shah, Philipp Hofer, Wen Yi Huang, Sergi Castellví-Bel, Susanna C. Larsson, Maria Dolores Chirlaque, Wei Zheng, Stephanie L. Schmit, Cecelia A. Laurie, Soo-Chin Lee, David Forman, Andrea N. Burnett-Hartman, Giovanna Masala, Sarah C. Nelson, Michael O. Woods, Charles Kooperberg, Qing Zhang, Sonja I. Berndt, Christopher S. Carlson, Katja Butterbach, Hyeong Rok Kim, Rebecca D. Jackson, David Van Den Berg, Michael C. Bassik, Amanda J. Cross, Sushma S. Thomas, Clemens Schafmayer, Anna H. Wu, Douglas F. Easton, Robert W. Haile, Ludmila Vodickova, Graham G. Giles, Yu Ru Su, Jenny Chang-Claude, Lorena Moreno, Peter C. Scacheri, Stefanie Brezina, Min-Ho Shin, Steven Gallinger, Bethany Van Guelpen, Daniel D. Buchanan, Roger L. Milne, Stephen J. Chanock, Tin Louie, Tameka Shelford, Emily White, Kala Visvanathan, Loic Le Marchand, Veronika Vymetalkova, Roxann G. Ingersoll, Temitope O. Keku, Stephanie A. Bien, Fredrick R. Schumacher, Wan-Ling Hsu, Amanda E. Toland, John S. Grove, Noralane M. Lindor, Faye Elliott, Leon Raskin, Heather Hampel, Joshua D. Smith, Vicente Martín, David V. Conti, Sjoerd G. Elias, Henk J. van Kranen, Manish Gala, Daniela Seminara, Syed H.E. Zaidi, Suzanne M. Leal, Tilman Kühn, Korbinian Weigl, Marc J. Gunter, Cornelia M. Ulrich, Peyton Greenside, Victor Moreno, John D. Potter, Michael Hoffmeister, Eric J. Jacobs, Catherine M. Tangen, Jihyoun Jeon, Fränzel J.B. Van Duijnhoven, Andrew T. Chan, Stephen B. Gruber, John A. Baron, Alicja Wolk, Edith J. M. Feskens, Demetrius Albanes, Amit Joshi, Bette J. Caan, Polly A. Newcomb, Stéphane Bézieau, Elizabeth M. Gillanders, Anshul Kundaje, Elizabeth A. Platz, Michael Wainberg, Sun-Seog Kweon, C. Roland Wolf, Gemma Ibáñez-Sanz, Shuji Ogino, Emiko Kobayashi, Richard B. Hayes, Patrick S. Parfrey, Katarina Cuk, Stephen N. Thibodeau, Kenneth Offit, David Duggan, Sophia Harlid, Pavel Vodicka, Juergen Boehm, Christa Stegmaier, Jeroen R. Huyghe, Joseph Vijai, Sang-Hee Cho, Elizabeth W. Pugh, Rachel Pearlman, Alessio Naccarati, Marilena Melas, Graham Casey, Jane Romm, Stephan Buch, Phyllis J. Goodman, Albert de la Chapelle, John L. Hopper, Zsofia K. Stadler, Corinne E. Joshu, Liesel M. FitzGerald, Wolfgang Lieb, Aung Ko Win, Keith R. Curtis, Hermann Brenner, Christopher K. Edlund, Li Hsu, Conghui Qu, Peter T. Campbell, Robert E. Schoen, Heiner Boeing, D. Timothy Bishop, Kimberly F. Doheny, Sabina Sieri, Barbara L. Banbury, Mathieu Lemire, Jane C. Figueiredo, Gregory Idos, Katerina Shulman, Thomas J. Hudson, Melissa C. Southey, Duncan C. Thomas, Paul D.P. Pharoah, Mila Pinchev, Vittorio Perduca, Rocky Fischer, Volker Arndt, William M. Grady, Nasa Sinnott-Armstrong, N. Charlotte Onland-Moret, David M. Levine, Li Li, Dallas R. English, Health Research Board - Ireland, Department of Medical Genetics, HMNC Brain Health, Case Western Reserve University [Cleveland], National Cancer Institute, NIH, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Service de Génétique, Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Division of Cancer Epidemiology, Cancer Genome Project, The Wellcome Trust Sanger Institute [Cambridge], Division of Signaling Biology, Ontario Cancer Institute, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), National Institute of Standards and Technology [Gaithersburg] (NIST), Ohio State University [Columbus] (OSU), Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Epidemiology Centre, Cancer Council Victoria, Division of Human Nutrition, Wageningen University and Research [Wageningen] (WUR), Division of Public Health Sciences, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Northern and Yorkshire Cancer Registry and Information Service, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, London School of Hygiene and Tropical Medicine (LSHTM), Fraunhofer Institute for Manufacturing Engineering and Automation (Fraunhofer IPA), Fraunhofer (Fraunhofer-Gesellschaft), Centre for Molecular , Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne-Centre for Molecular, Melbourne School of Population Health, Department of Mathematics, University of Warwick, Warwick Mathematics Institute (WMI), University of Warwick [Coventry]-University of Warwick [Coventry], Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Tata Memorial Centre, Cancer Epidemiology Unit, University of Oxford [Oxford], Thermo Fisher Scientific, Thermo Fisher Scientific Inc., Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, National University Health System, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Dell-EMC, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Pathology, Brigham and Women's Hospital [Boston], University Medical Center [Utrecht], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, Department of Epidemiology and Biostatistics, Imperial College London, Department of Visceral and Thoracic Surgery [Kiel, Germany], University Hospital Schleswig-Holstein [Kiel, Germany], Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, Department of Laboratory Medicine and Department of Pathology, Mayo Clinic College of Medicine, Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Dundee Technopole, CXR Biosciences Ltd, Karolinska Institutet [Stockholm], CINTRA / SEEE Nanyang Technological University, Nanyang Technological University [Singapour], Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology (MIT), Department of Preventive Medicine, University of Southern California (USC), Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Medstar Research Institute, Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Wageningen University and Research Centre [Wageningen] (WUR), Mount Sinai Hospital (MSH), Fraunhofer Institute for Manufacturing Engineering and Automation [Stuttgart] (IPA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Czech Academy of Sciences [Prague] (ASCR), Huyghe, Jeroen R [0000-0001-6027-9806], Harrison, Tabitha A [0000-0002-4173-7530], Chen, Sai [0000-0003-3106-5643], Schmit, Stephanie L [0000-0001-5931-1194], Jeon, Jihyoun [0000-0001-7003-3412], Schumacher, Fredrick R [0000-0002-3073-7463], Nelson, Sarah C [0000-0002-2109-6465], Sinnott-Armstrong, Nasa A [0000-0003-4490-0601], Alonso, M Henar [0000-0003-0285-5451], Arndt, Volker [0000-0001-9320-8684], Bézieau, Stéphane [0000-0003-0095-1319], Bishop, D Timothy [0000-0002-8752-8785], Brezina, Stefanie [0000-0001-5238-6900], Buchanan, Daniel D [0000-0003-2225-6675], Chanock, Stephen J [0000-0002-2324-3393], de la Chapelle, Albert [0000-0001-9345-9248], Easton, Douglas F [0000-0003-2444-3247], Hampe, Jochen [0000-0002-2421-6127], Hayes, Richard B [0000-0002-0918-661X], Hofer, Philipp [0000-0003-2550-6019], Huang, Wen-Yi [0000-0002-4440-3368], Hudson, Thomas J [0000-0002-1376-4849], Jacobs, Eric J [0000-0002-8458-7659], Jenkins, Mark A [0000-0002-8964-6160], Joshi, Amit D [0000-0001-7581-6934], Küry, Sébastien [0000-0001-5497-0465], Larsson, Susanna C [0000-0003-0118-0341], Laurie, Cecelia A [0000-0001-6569-2501], Martín, Vicente [0000-0003-0552-2804], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger L [0000-0001-5764-7268], Naccarati, Alessio [0000-0001-5774-0905], Newcomb, Polly A [0000-0001-8786-0043], Pardini, Barbara [0000-0001-9571-4257], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul DP [0000-0001-8494-732X], Raskin, Leon [0000-0003-1195-7214], Rennert, Gad [0000-0002-8512-068X], Shin, Min-Ho [0000-0002-2217-5624], Toland, Amanda E [0000-0002-0271-1792], Vijai, Joseph [0000-0002-7933-151X], Weigl, Korbinian [0000-0003-4453-2036], Win, Aung Ko [0000-0002-2794-5261], Wolk, Alicja [0000-0001-7387-6845], Zheng, Wei [0000-0003-1226-070X], Bassik, Michael C [0000-0001-5185-8427], Moreno, Victor [0000-0002-2818-5487], Peters, Ulrike [0000-0001-5666-9318], and Apollo - University of Cambridge Repository

Subjects
Male, Nutrition and Disease, Colorectal cancer, IDENTIFIES 6, Genome-wide association study, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Genotype, ComputingMilieux_MISCELLANEOUS, Avaluació del risc per la salut, Genetics & Heredity, Genetics, 0303 health sciences, COLON-CANCER, 11 Medical And Health Sciences, Middle Aged, 3. Good health, Medical genetics, Female, RNA, Long Noncoding, Colorectal Neoplasms, Life Sciences & Biomedicine, Signal Transduction, EXPRESSION, medicine.medical_specialty, SUSCEPTIBILITY LOCI, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, Article, Health risk assessment, 03 medical and health sciences, QUALITY-CONTROL, Càncer colorectal, Journal Article, medicine, Life Science, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, VLAG, Aged, 030304 developmental biology, Global Nutrition, [SDV.GEN]Life Sciences [q-bio]/Genetics, Wereldvoeding, Science & Technology, ORGAN SIZE, MUTATIONS, Haplotype, Case-control study, 06 Biological Sciences, medicine.disease, Genetic architecture, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human genome, LYSOPHOSPHATIDIC ACID, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P, Reporting Summary. Further information on experimental design is available in the Life Sciences Reporting Summary linked to this article.

Published
2018
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6. Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis

Author

Michael O. Woods, Fränzel J.B. van Duijnhoven, Tilman Kühn, Graham G. Giles, Temitope O. Keku, Konstantinos K. Tsilidis, Andrew T. Chan, Mingyang Song, Michael Hoffmeister, Gad Rennert, Tabitha A. Harrison, Anna H. Wu, Kenneth Offit, Mark A. Jenkins, Elizabeth A Platz, Sabina Sieri, Noralane M Lindor, John D. Potter, D Timothy Bishop, Barbara L. Banbury, Anne M. May, Sonja I. Berndt, José María Huerta, Antonia Trichopoulou, Paul D.P. Pharoah, Niki Dimou, Christopher I. Li, Roger L. Milne, Marc J. Gunter, Hermann Brenner, Martha L. Slattery, Catherine M. Tangen, Gianluca Severi, Richard M. Martin, Nabila Kazmi, Ruth C. Travis, Sanford D. Markowitz, Jeroen R. Huyghe, Heather Hampel, Ulrike Peters, John L. Hopper, Brigid M. Lynch, Krasimira Aleksandrova, Alicja Wolk, Merete Ellingjord-Dale, Li Li, Bethany Van Guelpen, Sergi Castellví-Bel, Edward Giovannucci, Steven J Gallinger, Annika Lindblom, Cornelia M. Ulrich, Stephen B. Gruber, Stephanie L. Schmit, Jenny Chang-Claude, Lorena Moreno, Victor Moreno, Nikos Papadimitriou, Stephen N. Thibodeau, Elio Riboli, Sophia Harlid, Polly A. Newcomb, Pavel Vodicka, Demetrius Albanes, Bas Bueno-de-Mesquita, Maria J. Sánchez, Sarah J Lewis, Timothy Robinson, Daniel D Buchanan, Loic Le Marchand, Carlo La Vecchia, Robert E Schoen, Neil Murphy, Giovanna Masala, Evelyn M. Monninkhof, Jane C. Figueiredo, Andrea Gsur, Jochen Hampe, Vittorio Perduca, Li Hsu, Emily White, Peter T. Campbell, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Epidemiology, German Institute of Human Nutrition, Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), The Cancer, Ageing and Somatic Mutation Programme [Cambridgeshire, UK], The Wellcome Trust Sanger Institute [Cambridge], Division of Cancer Epidemiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Harvard School of Public Health, Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medical Department 1 [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Ohio State University [Columbus] (OSU), FESTO, Universität Stuttgart [Stuttgart], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Genetics, HMNC Brain Health, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), University of Hawai‘i [Mānoa] (UHM), Chinese Center for Disease Control and Prevention, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Mayo Clinic, Case Western Reserve University [Cleveland], Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Cancer Epidemiology Centre, Cancer Council Victoria, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Memorial Sloane Kettering Cancer Center [New York], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, University of Cambridge [UK] (CAM), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, School of Public Health [London, UK] (Faculty of Medicine), Andalusian School of Public Health [Granada], Istituto Nazionale dei Tumori, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Mayo Clinic [Rochester], University of Oxford [Oxford], WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Karolinska Institutet [Stockholm], Nutrition and Metabolism Section, International Agency for Research on Cancer, [Papadimitriou,N, Dimou,N, Gunter,MJ, Murphy,N] Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Tsilidis,KK, Ellingjord-Dale,M, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Banbury,B, Harrison,TA, Hsu,L, Huyghe,JR, Li,CI, Newcomb,PA, Potter,JD, White,E, Peters,U] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Martin,RM, Kazmi,N] MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. [Martin,RM, Lewis,SJ, Robinson,TM] Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK. [Martin,RM] National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK. [Albanes,D, Berndt,SI] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MA, USA. [Aleksandrova,K] German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Bishop,DT] Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK. [Brenner,H, Hoffmeister,M] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Brenner,H] Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. [Brenner,H] German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. [Buchanan,DD, Giles,GG, Hopper,JL, Jenkins,MA, Lynch,B, Milne,R] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. [Buchanan,DD] Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Buchanan,DD] Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia [Bueno-de-Mesquita,B] Former senior scientist, Dept. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), BA Bilthoven, Netherlands. [Bueno-de-Mesquita,B] Former associate professor, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands. [Bueno-de-Mesquita,B] ormer visiting professor, Dept. of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary’s Campus, Norfolk Place, London, London, UK. [Bueno-de-Mesquita,B] Former academic Icon / visiting professor, Dept. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, Kuala Lumpur, Malaysia. [Campbell,PT] Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA. [Castellví-Bel,S, Moreno,L] Gastroenterology Department, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain. [Chan,AT, Song,M] Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chan,AT, Song,M] Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chang-Claude,J, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Chang-Claude,J] University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany. [Figueiredo,JC] Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [Figueiredo,JC] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gallinger,SJ] Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. [Giles,GG, Milne,R] Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia. [Giovannucci,E, Song,M] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. [Giovannucci,E, Song,M] Department of Nutrition, T.H. H, Chan School of Public Health, Boston, MA, USA. [Giovannucci,E] Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Gruber,SB, Schmit,SL] Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gsur,A] Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria. [Hampe,J] Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany. [Hampel,H] Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. [Harlid,S] Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden. [Hopper,JL] Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea. [Hsu,L] Department of Biostatistics, University of Washington, Seattle, WA, USA. [Huerta,JM, Moreno,V, Sánchez,MJ] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Keku,TO] Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA. [La Vecchia,C, Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [La Vecchia,C] Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy. [Le Marchand,L] University of Hawaii Cancer Center, Honolulu, HI, USA. [Li,L] Department of Family Medicine, University of Virginia, Charlottesville, VA, USA. [Lindblom,A] Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. [Lindblom,A] Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. [Lindor,NM] Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA. [Lynch,B] Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. [Markowitz,SD] Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH, USA. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [May,AM, Monninkhof,E] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA UTRECHT, Netherlands. [Milne,R] Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Moreno,V] Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Moreno,V] Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain. [Newcomb,PA] School of Public Health, University of Washington, Seattle, WA, USA. [Offit,K] Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. [Offit,K] Department of Medicine, Weill Cornell Medical College, New York, NY, USA. [Perduca,V, Severi,G] CESP, Fac. de médecine - Univ. ParisSud, Fac. de médecine - UVSQ I, Université Paris-Saclay, Villejuif, France. [Perduca,V, Severi,G] Gustave Roussy, Villejuif, France. [Perduca,V] Laboratoire de Mathématiques Appliquées MAP5 (UMR CNRS 8145), Université Paris Descartes, Paris, France. [Pharoah,PDP] Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Platz,EA] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. [Rennert,G] Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel. [Rennert,G] 7Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. [Rennert,G] Clalit National Cancer Control Center, Haifa, Israel. [Sánchez,MJ] Andalusian School of Public Health, Biomedical Research Institute ibs.GRANADA, University of Granada, Granada, Spain. [Schmit,SL] Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. [Schoen,RE] Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Slattery,ML] Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. [Tangen,CM] SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Thibodeau,SN] Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Ulrich,CM] Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. [van Duijnhoven,FJB] Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands. [Van Guelpen,B] Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden. [Van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Vodicka,P] Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic. [Vodicka,P] Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic. [Vodicka,P] Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic. [White,E, Peters,U] Department of Epidemiology, University of Washington, Seattle, WA, USA. [Wolk,A] Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. [Woods,MO] Memorial University of Newfoundland, Discipline of Genetics, St. John’s, Canada. [Wu,AH] University of Southern California, Preventative Medicine, Los Angeles, CA, USA., This work was supported by the National Cancer Institute, the International Agency for Research on Cancer and a Cancer Research UK program grant (C18281/A19169 to RMM, SJL & NK). RMM was supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funding sources for BCAC, CCFR, GECCO, and CORECT consortia are presented in detail in the appendix in the Supplementary material., Tsilidis, Konstantinos K [0000-0002-8452-8472], Martin, Richard M [0000-0002-7992-7719], Lewis, Sarah J [0000-0003-4311-6890], Robinson, Timothy M [0000-0003-0933-646X], Timothy Bishop, D [0000-0002-8752-8785], Buchanan, Daniel D [0000-0003-2225-6675], Chan, Andrew T [0000-0001-7284-6767], Giles, Graham G [0000-0003-4946-9099], Gsur, Andrea [0000-0002-9795-1528], Hampe, Jochen [0000-0002-2421-6127], Hampel, Heather [0000-0001-7558-9794], Harlid, Sophia [0000-0001-8540-6891], Harrison, Tabitha A [0000-0002-4173-7530], María Huerta, José [0000-0002-9637-3869], Huyghe, Jeroen R [0000-0001-6027-9806], Jenkins, Mark A [0000-0002-8964-6160], La Vecchia, Carlo [0000-0003-1441-897X], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger [0000-0001-5764-7268], Moreno, Victor [0000-0002-2818-5487], Newcomb, Polly A [0000-0001-8786-0043], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul D P [0000-0001-8494-732X], Potter, John D [0000-0001-5439-1500], Rennert, Gad [0000-0002-8512-068X], Riboli, Elio [0000-0001-6795-6080], Schmit, Stephanie L [0000-0001-5931-1194], Schoen, Robert E [0000-0001-7153-2766], Van Guelpen, Bethany [0000-0002-9692-101X], Wolk, Alicja [0000-0001-7387-6845], Peters, Ulrike [0000-0001-5666-9318], Murphy, Neil [0000-0003-3347-8249], Apollo - University of Cambridge Repository, Tsilidis, Konstantinos K. [0000-0002-8452-8472], Martin, Richard M. [0000-0002-7992-7719], Lewis, Sarah J. [0000-0003-4311-6890], Timothy Bishop, D. [0000-0002-8752-8785], Buchanan, Daniel D. [0000-0003-2225-6675], Chan, Andrew T. [0000-0001-7284-6767], Giles, Graham G. [0000-0003-4946-9099], Harrison, Tabitha A. [0000-0002-4173-7530], Huyghe, Jeroen R. [0000-0001-6027-9806], Jenkins, Mark A. [0000-0002-8964-6160], Newcomb, Polly A. [0000-0001-8786-0043], Pharoah, Paul D. P. [0000-0001-8494-732X], Potter, John D. [0000-0001-5439-1500], Schmit, Stephanie L. [0000-0001-5931-1194], Schoen, Robert E. [0000-0001-7153-2766], and Pharoah, Paul DP [0000-0001-8494-732X]

Subjects
Oncology, Epidemiology, Colorectal cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Accelerometry [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Molecular Epidemiology::Mendelian Randomization Analysis [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Epidemiology of cancer, Accelerometry, Odds Ratio, lcsh:Science, skin and connective tissue diseases, Cancer genetics, ComputingMilieux_MISCELLANEOUS, Cancer, 0303 health sciences, Biobank, 3. Good health, 030220 oncology & carcinogenesis, ICEP, Factores de riesgo, medicine.medical_specialty, Science, 631/67/2324, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colorectal Neoplasms, Hereditary Nonpolyposis [Medical Subject Headings], Breast Neoplasms/genetics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Exercise [Medical Subject Headings], Humans, Epidemiologia, Exercise, VLAG, Cancer och onkologi, 45, 631/67/1347, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Colorectal Neoplasms/genetics, 030104 developmental biology, Analyses, Risk factors, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, lcsh:Q, Breast neoplasms, 0301 basic medicine, 631/67/1504/1885, Nutrition and Disease, General Physics and Astronomy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Risk Factors, Neoplasias colorrectales, Voeding en Ziekte, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], Multidisciplinary, article, Public Health, Global Health, Social Medicine and Epidemiology, Polymorphism, Single Nucleotide/genetics, Ejercicio físico, Neoplasias de la mama, Female, Colorectal Neoplasms, 631/67, 141, Breast Neoplasms, 45/23, Polymorphism, Single Nucleotide, Colorectal neoplasms, Càncer de mama, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], Cancer epidemiology, 631/67/68, Internal medicine, Mendelian randomization, medicine, Journal Article, Life Science, Genetic Predisposition to Disease, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], business.industry, General Chemistry, Physical fitness, Confidence interval, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Condició física
Abstract

Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI), International Agency for Research on Cancer, Cancer Research UK C18281/A19169, National Institute for Health Research (NIHR)

Published
2020
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7. Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses

Author

Elio Riboli, Jochen Hampe, Ruth C. Travis, Andrea N. Burnett-Hartman, Anna H. Wu, Steven Gallinger, Stephen B. Gruber, Christopher I. Li, Bethany Van Guelpen, Kala Visvanathan, Loic Le Marchand, Veronika Vymetalkova, Demetrius Albanes, Jeroen R. Huyghe, Lori C. Sakoda, Jennifer Ose, Daniel D. Buchanan, Kenneth Offit, D. Timothy Bishop, John D. Potter, Sonja I. Berndt, Neil Murphy, Vittorio Perduca, Roger L. Milne, Niki Dimou, Marc J. Gunter, Ulrike Peters, Wen Yi Huang, Sergi Castellví-Bel, Graham Casey, Robert E. Schoen, Martha L. Slattery, Kathryn E. Bradbury, Albert de la Chapelle, Temitope O. Keku, Andrea Gsur, Wei Zheng, Gad Rennert, Hermann Brenner, Tabitha A. Harrison, Claudia Agnoli, Fränzel J.B. Van Duijnhoven, Sabina Rinaldi, Catherine M. Tangen, Jane C. Figueiredo, Ludmila Vodickova, Andrew T. Chan, Tilman Kühn, Hansong Wang, Mingyang Song, Sun-Seog Kweon, Annika Lindblom, Amanda I. Phipps, Cornelia M. Ulrich, Victor Moreno, Mark A. Jenkins, Li Hsu, Emily White, Conghui Qu, Peter T. Campbell, Stéphane Bézieau, Nikos Papadimitriou, Michael O. Woods, Jelena Bešević, Polly A. Newcomb, Pavel Vodicka, Heather Hampel, Barbara L. Banbury, Amanda J. Cross, Robert Carreras-Torres, Alicja Wolk, Graham G. Giles, Michael Hoffmeister, Elizabeth A. Platz, N. Charlotte Onland-Moret, Dallas R. English, Li Li, Jenny Chang-Claude, Vicente Martín, Richard M. Martin, María Dolores Chirlaque, Konstantinos K. Tsilidis, Clemens Schafmayer, Shuji Ogino, Nutrition and Metabolism Section, International Agency for Research on Cancer, Centre international de Recherche sur le Cancer (CIRC), School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Nuffield Department of Population Health - Cancer Epidemiology Unit, University of Oxford [Oxford], International Agency for Cancer Research (IACR), School of Public Health [London, UK] (Faculty of Medicine), Candiolo Cancer Institute (IRCCS), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Interactions récepteurs ligands en immunocancérologie et immunopathologie, IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), St. James's University Hospital, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University Medical Center [Utrecht], The Cancer, Ageing and Somatic Mutation Programme [Cambridgeshire, UK], The Wellcome Trust Sanger Institute [Cambridge], Department of Preventive Medicine, University of Southern California (USC), Division of Cancer Epidemiology, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Ohio State University [Columbus] (OSU), Cancer Epidemiology Centre, Cancer Council Victoria, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medical Department 1 [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), FESTO, Universität Stuttgart [Stuttgart], Division of Cancer Epidemiology and Genetics, Department of Medical Genetics, HMNC Brain Health, University of Hawai‘i [Mānoa] (UHM), Chinese Center for Disease Control and Prevention, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Dell-EMC, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Memorial Sloane Kettering Cancer Center [New York], Department of Pathology, Brigham and Women's Hospital [Boston], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Department of Visceral and Thoracic Surgery [Kiel, Germany], University Hospital Schleswig-Holstein [Kiel, Germany], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Karolinska Institutet [Stockholm], and Center for Astrophysical Sciences [Baltimore]

Subjects
Oncology, Male, Nutrition and Disease, Colorectal cancer, BMI, body mass index, PLASMA-INSULIN, IGFBP3, IGF1, insulin-like growth factor 1, Genome-wide association study, GWAS, genome-wide association studies, MR-PRESSO, Mendelian Randomization Pleiotropy RESidual Sum and Outlier, FACTOR (IGF)-I, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Insulina, Medicine, Insulin, GWAS, Registries, Insulin-Like Growth Factor I, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, ICC, intraclass correlation coefficient, Incidence, Hazard ratio, MR, Mendelian randomization, Gastroenterology, MEN, SNP, single nucleotide polymorphism, Middle Aged, SERUM-LEVELS, 3. Good health, IGF-I, CRC, 030220 oncology & carcinogenesis, CRP, C-reactive protein, Female, Colorectal Neoplasms, Life Sciences & Biomedicine, Medical Genetics, REGRESSION DILUTION, Signal Transduction, medicine.medical_specialty, HbA1c, glycolated hemoglobin, FACTOR-I, Polymorphism, Single Nucleotide, Risk Assessment, Article, C-PEPTIDE, 03 medical and health sciences, Sex Factors, Insulin-Like Growth Factor II, Càncer colorectal, Internal medicine, COLON, Mendelian randomization, Biomarkers, Tumor, Journal Article, Humans, IGFBP3, insulin-like growth factor binding protein 3, 030304 developmental biology, Aged, VLAG, Medicinsk genetik, Cancer och onkologi, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Case-control study, Cancer, IGFBP-3, 1103 Clinical Sciences, Odds ratio, Mendelian Randomization Analysis, medicine.disease, HR, hazard ratio, United Kingdom, CI, confidence interval, OR, odds ratio, Insulin-Like Growth Factor Binding Protein 3, Case-Control Studies, Cancer and Oncology, SHBG, sex hormone binding globulin, 1114 Paediatrics and Reproductive Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, SD, standard deviation, 1109 Neurosciences, Follow-Up Studies
Abstract

Background & Aims Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development. Methods Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) Results After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05–1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03–1.12; P = 3.3 × 10–4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06–1.18; P = 4.2 × 10–5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2. Conclusions In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis., Graphical abstract

Published
2020
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8. Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers

Author

Mavaddat, N., Antoniou, A.C., Mooij, T.M., Hooning, M.J., Heemskerk-Gerritsen, B.A., Nogues, C., Laborde, L., Breysse, E., Stoppa-Lyonnet, D., Gauthier-Villars, M., Buecher, B., Caron, O., Fourme-Mouret, E., Fricker, J.P., Lasset, C., Bonadona, V., Berthet, P., Faivre, L., Luporsi, E., Mari, V., Gladieff, L., Gesta, P., Sobol, H., Eisinger, F., Longy, M., Dugast, C., Colas, C., Coupier, I., Pujol, P., Corsini, C., Lortholary, A., Vennin, P., Adenis, C., Nguyen, T.D., Delnatte, C., Tinat, J., Tennevet, I., Limacher, J.M., Maugard, C., Bignon, Y.J., Demange, L., Penet, C., Dreyfus, H., Cohen-Haguenauer, O., Venat-Bouvet, L., Leroux, D., Zattara-Cannoni, H., Fert-Ferrer, S., Bera, O., Ellis, S., Barrowdale, D., Frost, D., Evans, D.G., Izatt, L., Adlard, J., Eeles, R., Brewer, C., Tischkowitz, M., Henderson, A., Cook, J., Eccles, D., Hogervorst, F.B.L., Collee, J.M., Asperen, C.J. van, Mensenkamp, A.R., Ausems, M.G.E.M., Meijers-Heijboer, H.E.J., Engelen, K. van, Blok, M.J., Oosterwijk, J.C., Verloop, J., Broek, E. van den, Mourits, M.J.E., Koppert, L.B., Hopper, J.L., John, E.M., Chung, W.K., Andrulis, I.L., Daly, M.B., Buys, S.S., Benitez, J., Caldes, T., Jakubowska, A., Simard, J., Singer, C.F., Tan, Y., Olah, E., Navratilova, M., Foretova, L., Gerdes, A.M., Roos-Blom, M.J., Leeuwen, F.E. van, Arver, B., Olsson, H., Schmutzler, R.K., Engel, C., Kast, K., Phillips, K.A., Terry, M.B., Milne, R.L., Goldgar, D.E., Rookus, M.A., Andrieu, N., Easton, D.F., GENEPSO, EMBRACE, HEBON, kConFab Investigators, IBCCS, kConFab, BCFR, University of Cambridge [UK] (CAM), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Erasmus MC Cancer Institute, Rotterdam, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Curie [Paris], Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Catherine-de-Sienne [Nantes] (CCS), Manchester University NHS Foundation Trust (MFT), Guy's & St Thomas' NHS Foundation Trust, Chapel Allerton Hospital, University of Leeds, Royal Marsden NHS Foundation Trust, Royal Devon & Exeter Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Sheffield Children's NHS Foundation Trust, Wessex clinical genetics service, Vrije Universiteit Amsterdam [Amsterdam] (VU), University Medical Center Groningen [Groningen] (UMCG), Department of Medical Genetics, University Medical Center [Utrecht], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, Department of Epidemiology, Cancer Prevention Institute of California, Columbia University [New York], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Division of Population Science, Fox Chase Cancer Center, Department of Internal Medicine, Huntsman Cancer Institute, Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Medizinische Universität Wien = Medical University of Vienna, National Institute of Oncology, Masaryk Memorial Cancer Institute (MMCI), Masaryk University [Brno] (MUNI), Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, The Netherlands Cancer Institute [Amsterdam, The Netherlands], Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Oncology, Lund University Hospital, Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Dept of Haematology and Medical Oncology, Peter MacCallum Cancer Center, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Cancer Epidemiology Centre, Cancer Council Victoria, International Agency for Cancer Research (IACR), Netherlands Cancer Institute, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Andrieu, Nadine, Human genetics, Epidemiology and Data Science, Mavaddat, Nasim [0000-0003-0307-055X], Eeles, Ros [0000-0002-3698-6241], Engel, Christoph [0000-0002-7247-282X], Apollo - University of Cambridge Repository, Pomeranian Medical University-International Hereditary Cancer Centre, Masaryk Memorial Cancer Institute (RECAMO), Columbia Mailman School of Public Health-Columbia University [New York], Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Antoniou, Antonis [0000-0001-9223-3116], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Medical Oncology, Surgery, Cancer Research UK (Reino Unido), NIH - National Cancer Institute (NCI) (Estados Unidos), United States Department of Health and Human Services, Ministerio de Economía y Competitividad (España), Unión Europea. Comisión Europea. European Research Council (ERC), Norwegian EEA Financial Mechanism, Hungarian Scientific Research Fund (Hungría), Ministry of Education, Youth and Sports (República Checa), MH CZ -DRO (MMCI), National Health and Medical Research Council (Australia), Australian National Breast Cancer Foundation, Cancer Australia, ERA-NET TRANSAN JTC 2012 Cancer, Transcan grant, Biotechnology and Biological Sciences Research Council (Reino Unido), Pink Ribbons Project, Netherlands Organisation of Scientific Research, Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Deutsche Krebshilfe, National Institute for Health Research (Reino Unido), Unión Europea. Comisión Europea. 7 Programa Marco, Ministry of Economic Development, Innovation and Export Trade-grant, Canadian Institutes of Health Research, Cancer Research UK, NIH National Cancer Institute (NCI), United States Department of Health & Human Services National Institutes of Health (NIH) - USA, Ministerio de Economia y Competividad (MINECO), European Research Council (ERC), Hungarian Research Grants, MEYS -NPS I, National Health and Medical Research Council of Australia, BBMRI grant, Pink Ribbon grants, Netherlands Organisation of Scientific Research grant, KWF Kankerbestrijding, Instituto de Salud Carlos III - ISCIII, National Institute for Health Research (NIHR), European Union Seventh Framework Program (2007-2013), Canadian Institutes of Health Research (CIHR), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), United States of Department of Health & Human Services, European Research Council, APH - Quality of Care, APH - Methodology, Graduate School, ARD - Amsterdam Reproduction and Development, RS: GROW - R4 - Reproductive and Perinatal Medicine, and MUMC+: DA KG Lab Centraal Lab (9)

Subjects
endocrine system diseases, SURGERY, [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, Cohort Studies, 0302 clinical medicine, BRCA2 Mutation, Breast cancer, Surgical oncology, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, Salpingo-oophorectomy/methods, 0303 health sciences, Natural menopause, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Obstetrics, BRCA1 Protein, Breast Neoplasms/epidemiology, Incidence (epidemiology), Incidence, WOMEN, ASSOCIATION, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, OVARIAN, BRCA2 Protein/genetics, 3. Good health, Menopause, Risk-reducing salpingo-oophorectomy, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SURVIVAL, Female, Research Article, Cohort study, Adult, medicine.medical_specialty, Salpingo-oophorectomy, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, lcsh:RC254-282, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, METAANALYSIS, 030304 developmental biology, BRCA2 Protein, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, CONSORTIUM, risk-reducing salpingo-oophorectomy, International Agencies, medicine.disease, BRCA1, BRCA2, KCONFAB, REDUCTION, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, LINK, Mutation, BRCA1 Protein/genetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Risk Reduction Behavior
Abstract

The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO. The BCFR was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the BCFR. CNIO was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare Diseases (CIBERER). CNIO was also partially supported by FISPI16/00440. INHERIT was supported by the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program-grant #CRN-87521-and the Ministry of Economic Development, Innovation and Export Trade-grant #PSR-SIIRI-701. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (GPH-129344), the Ministere de l'Economie, de la Science et de l' Innovation du Quebec through Genome Quebec, and The Quebec Breast Cancer Foundation. Jacques Simard is a Chairholder of the Canada Research Chair in Oncogenetics. EMBRACE is supported by the Cancer Research UK grants C1287/A23382 and C1287/A16563. D. Gareth Evans is supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by the Cancer Research UK grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Antonis C. Antoniou is funded by Cancer Research UK grants C12292/A20861 and C12292/A11174. MT is funded by the European Union Seventh Framework Program (2007-2013)/European Research Council (310018). The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 110837, Rita K. Schmutzler). The national French cohort, GENEPSO, had been supported by a grant from the Fondation de France and the Ligue Nationale Contre le Cancer and is being supported by a grant from INCa as part of the European program ERA-NET on Translational Cancer Research (TRANSCAN-JTC2012, no. 2014-008). HCSC was supported by CIBERONC 161200301 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46, and the Transcan grant JTC 2012 Cancer 12-054. The IHCC was supported by Grant PBZ_ KBN_122/P05/2004 and ERA-NET TRANSAN JTC 2012 Cancer 12-054 (ERA-NET-TRANSCAN/07/2014). This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195); the Australian National Breast Cancer Foundation (IF 17); the National Health and Medical Research Council (454508, 288704, 145684); the National Institute of Health U.S.A. (1RO1CA159868); the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; and the Cancer Foundation of Western Australia. KAP is an Australian National Breast Cancer Foundation fellow. MODSQUAD-Czech Republic, Brno, was supported by MH CZ -DRO (MMCI, 00209805) and by MEYS -NPS I -LO1413 to LF and MN. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, NKFI OTKA K-112228, and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced Grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society. The funders had no role in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. Sí

Published
2020
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9. Commentary: Special Report: The Biology of Inequalities in Health: The Lifepath Consortium

Author

Paolo Vineis, Mauricio Avendano-Pabon, Henrique Barros, Mel Bartley, Cristian Carmeli, Luca Carra, Marc Chadeau-Hyam, Giuseppe Costa, Cyrille Delpierre, Angelo D'Errico, Silvia Fraga, Graham Giles, Marcel Goldberg, Michelle Kelly-Irving, Mika Kivimaki, Benoit Lepage, Thierry Lang, Richard Layte, Frances MacGuire, Johan P. Mackenbach, Michael Marmot, Cathal McCrory, Roger L. Milne, Peter Muennig, Wilma Nusselder, Dusan Petrovic, Silvia Polidoro, Fulvio Ricceri, Oliver Robinson, Silvia Stringhini, Marie Zins, Imperial College London, King‘s College London, Epidemiology Research Unit [Porto, Portugal] (EPIUnit), Instituto de Saúde Pública [Porto, Portugal], Universidade do Porto = University of Porto-Universidade do Porto = University of Porto, University College of London [London] (UCL), Université de Lausanne = University of Lausanne (UNIL), Università degli studi di Torino = University of Turin (UNITO), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Piedmont Centre for Drug Addiction Epidemiology, ASLTO3, Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], University of Melbourne-Melbourne School for Population and Global Health, University of Melbourne, Monash University [Melbourne], Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Trinity College Dublin, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Columbia University [New York], Italian Institute for Genomic Medicine, Geneva University Hospital (HUG), Horizon 2020 grant number 633666- Swiss State Secretariat for Education, Research and Innovation SERI, European Project: 633666,H2020,H2020-PHC-2014-two-stage,LIFEPATH(2015), Commission of the European Communities, Medical Research Council (MRC), Instituto de Saúde Pública da Universidade do Porto, and Public Health

Subjects
[SDV]Life Sciences [q-bio], Psychological intervention, DETERMINANTS, 0302 clinical medicine, Policy and Practice Reviews, 030212 general & internal medicine, Longitudinal Studies, Social science, Child, MESH: Omics, media_common, Public, Environmental & Occupational Health, Executive summary, General Commentary, biology, 030503 health policy & services, lcsh:Public aspects of medicine, MESH: Healthy ageing, socioeconomic position, ASSOCIATION, Causality, Allostatic load, omics, MESH: Socioeconomic position, Europe, healthy aging, social determinants of health, philosophy of science, lifepath consortium, Life course approach, Public Health, 0305 other medical science, Life Sciences & Biomedicine, Adult, causality, Inequality, life-course, media_common.quotation_subject, MESH: Life-course, 1117 Public Health and Health Services, CONDITIONAL CASH TRANSFERS, social inequalities, 03 medical and health sciences, AGE, Environmental health, MESH: Biology, Humans, Social inequality, Social determinants of health, ALLOSTATIC LOAD, Socioeconomic status, Disadvantage, Sedentary lifestyle, ddc:613, ADVERSE CHILDHOOD EXPERIENCES, Philosophy of science, Science & Technology, Australia, Public Health, Environmental and Occupational Health, CAUSE-SPECIFIC MORTALITY, lcsh:RA1-1270, Health Status Disparities, health inequalities, Socioeconomic Factors, MESH: Social inequalities, RISK-FACTORS, OCCUPATIONAL CLASS
Abstract

Funded by the European Commission Horizon 2020 programme, the Lifepath research consortium aimed to investigate the effects of socioeconomic inequalities on the biology of healthy aging. The main research questions included the impact of inequalities on health, the role of behavioral and other risk factors, the underlying biological mechanisms, the efficacy of selected policies, and the general implications of our findings for theories and policies. The project adopted a life-course and comparative approach, considering lifetime effects from childhood and adulthood, and pooled data on up to 1.7 million participants of longitudinal cohort studies from Europe, USA, and Australia. These data showed that socioeconomic circumstances predicted mortality and functional decline as strongly as established risk factors currently targeted by global prevention programmes. Analyses also looked at socioeconomically patterned biological markers, allostatic load, and DNA methylation using richly phenotyped cohorts, unraveling their association with aging processes across the life-course. Lifepath studies suggest that socioeconomic circumstances are embedded in our biology from the outset—i.e., disadvantage influences biological systems from molecules to organs. Our findings have important implications for policy, suggesting that (a) intervening on unfavorable socioeconomic conditions is complementary and as important as targeting well-known risk factors, such as tobacco and alcohol consumption, low fruit and vegetable intake, obesity and a sedentary lifestyle, and that (b) effects of preventive interventions in early life integrate interventions in adulthood. The report has an executive summary that refers to the different sections of the main paper. This study was supported by the European Commission (Horizon 2020 grant number 633666) and the Swiss State Secretariat for Education, Research and Innovation SERI.

Published
2020
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10. Alcohol consumption, cigarette smoking, and risk of breast cancer for BRCA1 and BRCA2 mutation carriers: results from The BRCA1 and BRCA2 Cohort Consortium

Author

Terry, Mary Beth, Noguès, Catherine, Barrowdale, Daniel, Frost, Debra, Brewer, Carole, Evans, D. Gareth, Izatt, Louise, Side, Lucy, Walker, Lisa, Tischkowitz, Marc, Rogers, Mark, Porteous, Mary, Meijers-Heijboer, Hanne E.J., Gille, Johan JP, Blok, Marinus, Hoogerbrugge, Nicoline, Daly, Mary, Andrulis, Irene, Buys, Saundra, John, Esther, McLachlan, Sue-Anne, Friedlander, Michael, Tan, Yen, Osorio, Ana, Caldés, Trinidad, Jakubowska, Anna, Simard, Jacques, Singer, Christian, Olah, Edith, Navratilova, Marie, Foretova, Lenka, Gerdes, Anne-Marie, Roos-Blom, Marie-José, Arver, Brita, Olsson, Håkan, Schmutzler, Rita, Hopper, John, Milne, Roger, Easton, Douglas, Van Leeuwen, Flora, Rookus, Matti, Andrieu, Nadine, Goldgar, David, Huntsman Cancer Institute [Salt Lake City], University of Utah, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Department of Clinical Genetics, Royal Devon & Exeter Hospital, Genetic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre, University of Manchester, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Department of Clinical Genetics, The Churchill, Oxford, Oxford Regional Genetics Service [Oxford, UK], Churchill Hospital Oxford Centre for Haematology, Department of Genetics, Portuguese Oncology Institute, Department of Computer Science [Colorado State University], Colorado State University [Fort Collins] (CSU), West General Hospital, VU University Medical Center [Amsterdam], University Hospital Maastricht, Department of Human Genetics, Radboud University Medical Center [Nijmegen], Division of Population Science, Fox Chase Cancer Center, Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Internal Medicine, Huntsman Cancer Institute, Department of Epidemiology, Cancer Prevention Institute of California, St. Vincent's Hospital, Sydney, Dept of Medical Oncology, Division of Medicine, University of New South Wales [Sydney] (UNSW)-Prince of Wales Hospital Randwick, Medical University of Vienna, Human Genetics Group, Spanish National Cancer Research Centre, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Genetics and Pathology, Pomeranian Medical University-International Hereditary Cancer Centre, Laboratoire de Génomique des Cancers, Laval University [Québec], Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, National Institute of Oncology, Masaryk Memorial Cancer Institute (RECAMO), Odense University Hospital, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Oncology, Lund University Hospital, Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, Cancer Epidemiology Centre, Cancer Council Victoria, Centre for Cancer Genetic Epidemiology [Cambridge], Department of Oncology-University of Cambridge [UK] (CAM), Departments of Epidemiology and Molecular Pathology, The Netherlands Cancer Institute, Netherlands Cancer Institute, Innovation et Développement dans l'Agriculture et l'Agro-alimentaire (Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre national d'études agronomiques des régions chaudes (CNEARC)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Department of Dermatology [Salt Lake City, UT, USA], University of Utah School of Medicine [Salt Lake City], This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195, 1100868), the Australian National Breast Cancer Foundation (IF 17), the National Health and Medical Research Council (454508, 288704, 145684), the National Institute of Health U.S.A. (1RO1CA159868), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Kelly Phillips is an Australian National Breast Cancer Foundation fellow.Lenka Foretova was supported by MH CZ - DRO (MMCI, 00209805) and by MEYS - NPS I- LO1413 to LF, MN. Edith Olah and The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, NKFI OTKA K-112228 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/ÖP-9. Hakan Olsson and Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced Grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society., Medizinische Universität Wien = Medical University of Vienna, Université Laval [Québec] (ULaval), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], MINES ParisTech - École nationale supérieure des mines de Paris, and Université Paris sciences et lettres (PSL)

Subjects
breast cancer, endocrine system diseases, alcohol, cigarette smoking, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, skin and connective tissue diseases, BRCA1, BRCA2
Abstract

International audience; BACKGROUND:Tobacco smoking and alcohol consumption have been intensively studied in the general population to assess their effects on the risk of breast cancer (BC), but very few studies have examined these effects in BRCA1 and BRCA2 mutation carriers. Given the high BC risk for mutation carriers and the importance of BRCA1 and BRCA2 in DNA repair, better evidence on the associations of these lifestyle factors with BC risk is essential.METHODS:Using a large international pooled cohort of BRCA1 and BRCA2 mutation carriers, we conducted retrospective (5,707 BRCA1 mutation carriers; 3,525 BRCA2 mutation carriers) and prospective (2,276 BRCA1 mutation carriers; 1,610 BRCA2 mutation carriers) analyses of alcohol and tobacco consumption using Cox proportional hazards models.RESULTS:For both BRCA1 and BRCA2 mutation carriers, none of the smoking-related variables was associated with BC risk, except smoking for more than five years before a first full-term pregnancy (FFTP) when compared to parous women who never smoked. For BRCA1 mutation carriers, the HR from retrospective analysis (HRR) was 1.19 (95%CI:1.02,1.39) and the HR from prospective analysis (HRP) was 1.36 (95%CI:0.99,1.87). For BRCA2 mutation carriers, smoking for more than five years before a FFTP showed an association of a similar magnitude, but the confidence limits were wider (HRR=1.25,95%CI:1.01,1.55 and HRP=1.30,95%CI:0.83,2.01). For both carrier groups, alcohol consumption was not associated with BC risk.CONCLUSIONS:The finding that smoking during the pre-reproductive years increases BC risk for mutation carriers warrants further investigation.IMPACT:This is the largest prospective study of BRCA mutation carriers to assess these important risk factors.

Published
2019
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11. Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

Author

Paul Brennan, M. G. Ennas, Qing Lan, Sasha Bernatsky, Alan A. Arslan, Peter Kraft, Lohith Madireddy, Roel Vermeulen, Kenan Onel, Graham G. Giles, John J. Spinelli, Eleanor Kane, Bengt Glimelius, Alexandra Nieters, David V. Conti, Christine F. Skibola, Pouya Khankhanian, Amy Moore, Ruth C. Travis, Mads Melbye, Sonja I. Berndt, Mark Liebow, Lauren R. Teras, Pierluigi Cocco, Lennox Din, Alain Monnereau, Mark P. Purdue, Lenka Foretova, Stephen J. Chanock, Stephen M. Ansell, Angela Brooks-Wilson, Wendy Cozen, Kenneth Offit, Demetrius Albanes, Anne J. Novak, Melissa C. Southey, Paolo Boffetta, Nicola J. Camp, James R. Cerhan, Rudolph Kaaks, Silvia de Sanjosé, Karen Curtin, Sophia S. Wang, James McKay, Nicole Wong Doo, Hans-Olov Adami, Tongzhang Zheng, Claire M. Vajdic, Nisha Pradhan, Giacomo Muzi, Gilles Salles, Nathaniel Rothman, Yolanda Benavente, Marc Maynadié, Brian K. Link, Delphine Casabonne, Hervé Ghesquières, Joseph Vijai, Karin E. Smedby, Paige M. Bracci, David G. Cox, Brenda M. Birmann, Lucia Miligi, Carolyn Stewart, Lucia Conde, Leonid Padyukov, Eve Roman, Richard K. Severson, Jorge R. Oksenberg, Immaculata De Vivo, Yawei Zhang, Corrado Magnani, Jacqueline Clavel, Lindsay M. Morton, Corinne Haioun, Jonathan N. Hofmann, Karen H. Costenbader, Pierre-Antoine Gourraud, Mohammad Sheikh, Stephanie J. Weinstein, Susan L. Slager, Paolo Vineis, Nikitha Kosaraju, Zachary Taub, Henrik Hjalgrim, Roger L. Milne, Morris Din, Martha Glenn, Nikolaus Becker, Timothy J. Vyse, Thomas M. Mack, Anthony Staines, Department of Medicine, Clinical Epidemiology, McGill University Health Center [Montreal] (MUHC), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Emory University [Atlanta, GA], Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, International Agency for Cancer Research (IACR), Department of Public Health, Vientiane Municipality, Registre des hémopathies malignes de Côte d'Or, Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, GRAPHOS - IFROSS Recherche, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Faculty of Medicine, Section of Rheumatology, Imperial College London, Karolinska Institutet [Stockholm], Epidémiologie environnementale des cancers, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Uppsala Universitet [Uppsala], Carver College of Medicine, University of Iowa, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Division of Cancer Epidemiology and Genetics, National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Health Sciences, University of York [York, UK], Service de Radio-Oncologie [Lyon], Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), University of Melbourne, Centre Léon Bérard [Lyon], Mayo Clinic [Rochester], Occupational and Environmental Epidemiology Branch [Bethesda, Maryland], Division of Cancer Epidemiology and Genetics [Bethesda, Maryland], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), Memorial Sloane Kettering Cancer Center [New York], Huntsman Cancer Institute, Clinical Genetics Service, ISPO - Cancer Prevention and Research Institute, Unit of Environmental and Occupational Epidemiology, Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], B.B. Brodie Department of Neuroscience, Department of Pathology, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Unit of Environment Cancer Epidemiology, IARC, University of Torino and CPO-Piemonte, Università degli studi di Torino (UNITO), Department of Epidemiology, Harvard School of Public Health, Wayne State University [Detroit], Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Cancer Epidemiology Centre, Cancer Council Victoria, Cancer Epidemiology Unit, University of Oxford [Oxford], De la Molécule aux Nanos-objets : Réactivité, Interactions et Spectroscopies (MONARIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Catalan Institute of Oncology (ICO), Department of Neurology [San Francisco, CA, USA], University of California [San Francisco] (UCSF), University of California-University of California, Norris Comprehensive Cancer Center, Masaryk University [Brno] (MUNI), Università degli studi di Torino = University of Turin (UNITO), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Imperial College London, University of Oxford, Din L., Sheikh M., Kosaraju N., Smedby K.E., Bernatsky S., Berndt S.I., Skibola C.F., Nieters A., Wang S., McKay J.D., Cocco P., Maynadie M., Foretova L., Staines A., Mack T.M., de Sanjose S., Vyse T.J., Padyukov L., Monnereau A., Arslan A.A., Moore A., Brooks-Wilson A.R., Novak A.J., Glimelius B., Birmann B.M., Link B.K., Stewart C., Vajdic C.M., Haioun C., Magnani C., Conti D.V., Cox D.G., Casabonne D., Albanes D., Kane E., Roman E., Muzi G., Salles G., Giles G.G., Adami H.-O., Ghesquieres H., De Vivo I., Clavel J., Cerhan J.R., Spinelli J.J., Hofmann J., Vijai J., Curtin K., Costenbader K.H., Onel K., Offit K., Teras L.R., Morton L., Conde L., Miligi L., Melbye M., Ennas M.G., Liebow M., Purdue M.P., Glenn M., Southey M.C., Din M., Rothman N., Camp N.J., Wong Doo N., Becker N., Pradhan N., Bracci P.M., Boffetta P., Vineis P., Brennan P., Kraft P., Lan Q., Severson R.K., Vermeulen R.C.H., Milne R.L., Kaaks R., Travis R.C., Weinstein S.J., Chanock S.J., Ansell S.M., Slager S.L., Zheng T., Zhang Y., Benavente Y., Taub Z., Madireddy L., Gourraud P.-A., Oksenberg J.R., Cozen W., Hjalgrim H., Khankhanian P., and Le Bihan, Sylvie

Subjects
Oncology, Male, Multifactorial Inheritance, Lymphoma, Epidemiology, Chronic lymphocytic leukemia, Follicular lymphoma, Genome-wide association study, Disease, Neurodegenerative, meta-analysi, immune system diseases, HLA Antigens, Risk Factors, hemic and lymphatic diseases, 2.1 Biological and endogenous factors, HLA Antigen, Aetiology, Genetics (clinical), Cancer, Allele, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Lymphoma, Non-Hodgkin, non-Hodgkin lymphoma, 030305 genetics & heredity, Single Nucleotide, Hematology, Middle Aged, 3. Good health, Public Health and Health Services, Female, Human, medicine.medical_specialty, autoimmune disease, genome-wide association study, meta-analysis, Alleles, Autoimmune Diseases, Humans, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Non-Hodgkin, Article, 03 medical and health sciences, Rare Diseases, Internal medicine, Genetic variation, medicine, Genetics, Polymorphism, 030304 developmental biology, Autoimmune disease, business.industry, Multiple sclerosis, Risk Factor, Arthritis, Inflammatory and immune system, Human Genome, medicine.disease, Brain Disorders, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

Published
2019
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12. Plain packaging: legislative differences in Australia, France, the UK, New Zealand and Norway, and options for strengthening regulations

Author

Kylie Lindorff, Janne Scheffels, Crawford Moodie, Janet Hoek, Karine Gallopel-Morvan, University of Stirling, University of Otago [Dunedin, Nouvelle-Zélande], Norwegian Institute of Public Health [Oslo] (NIPH), École des Hautes Études en Santé Publique [EHESP] (EHESP), EA Management des Organisations de Santé (EA MOS), École des Hautes Études en Santé Publique [EHESP] (EHESP)-PRES Sorbonne Paris Cité, Institut du Management (IDM), and Cancer Epidemiology Centre, Cancer Council Victoria

Subjects
Health (social science), Time Factors, Public policy, Best practice, Global health, Legislation, Product Labeling, Terminology, 03 medical and health sciences, 0302 clinical medicine, Terminology as Topic, Milestone (project management), Product Packaging, Humans, 030212 general & internal medicine, Marketing, Government, 030505 public health, Public Health, Environmental and Occupational Health, Legislature, Tobacco Products, Quitline, Packaging, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Business, 0305 other medical science
Abstract

International audience; By July 2018, five countries (Australia, France, the UK, New Zealand and Norway) had fully implemented plain (standardised) packaging. Using government documents, we reviewed the key legislative differences between these five countries to identify best practice measures and potential lacuna. We then discuss how governments planning to introduce plain packaging could strengthen their legislation. Differences between countries include the terminology used (either ‘plain’, ‘standardised’ or ‘plain and standardised’), products covered and transition times (ranging from 2 to 12 months). Myriad differences exist with respect to the packaging, including the dimensions (explicitly stated for height, width and depth vs minimum dimensions for the health warnings only), structure (straight-edged flip-top packs vs straight, rounded and bevelled-edged flip-top packs and shoulder boxes) and size (minimum number of cigarettes and weight of tobacco vs fixed amounts) and warning content (eg, inclusion of a stop-smoking web address and/or quitline displayed on warnings on one or both principal display areas). Future options that merit further analysis include banning colour descriptors in brand and variant names, allowing pack inserts promoting cessation and permitting cigarettes that are designed to be dissuasive. Plain packaging legislation and regulations are divergent. Countries moving towards plain packaging should consider incorporating the strengths of existing policies and review opportunities for extending these. While plain packaging represents a milestone in tobacco-control policy, future legislation need not simply reflect the past but could set new benchmarks to maximise the potential benefits of this policy.

Published
2019
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13. A Collaborative Analysis of Individual Participant Data from 19 Prospective Studies Assesses Circulating Vitamin D and Prostate Cancer Risk

Author

Bernd Holleczek, Demetrius Albanes, Stephanie J. Weinstein, Yuen Y. E. Wong, Michael B. Cook, Alison M. Mondul, Konstantinos K. Tsilidis, Christopher A. Haiman, Jeannette M. Schenk, Kala Visvanathan, Loic Le Marchand, María José Sánchez, Pamela L. Lutsey, Freddie C. Hamdy, Harri Rissanen, Jenny L Donovan, Marc J. Gunter, David E. Neal, Shoichiro Tsugane, Bas Bueno-de-Mesquita, Tone Bjørge, Haakon E. Meyer, Rune Blomhoff, Mélanie Deschasaux, Mathilde Touvier, Pilar Galan, Lynne R. Wilkens, Tracy M. Layne, Johan Malm, Serge Hercberg, Timothy J. Key, Antonia Trichopoulou, Petra H.M. Peeters, Randi Elin Gislefoss, Amanda Black, Ruth C. Travis, Osvaldo P. Almeida, Domenico Palli, June M. Chan, Martin Almquist, Darryl W. Eyles, Elizabeth A. Williamson, Anja Olsen, Kathy J. Helzlsouer, Paul N. Appleby, Jonas Manjer, Hermann Brenner, Wen Yi Huang, Edward Giovannucci, Corinne E. Joshu, Regina G. Ziegler, Leon Flicker, Naomi E. Allen, Bu B. Yeap, Laura Perna, Giske Ursin, Meir J. Stampfer, Catherine M. Tangen, Richard M. Martin, Aurora Perez-Cornago, Norie Sawada, Paul Knekt, Ben Schöttker, Elizabeth A. Platz, Alicia K Heath, Dallas R. English, Nuffield Department of Population Health [Oxford], University of Oxford [Oxford], Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Division of Epidemiology and Community Health, University of Minnesota [Twin Cities], University of Minnesota System-University of Minnesota System, University of Michigan [Ann Arbor], University of Michigan System, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], National Institute for Public Health and the Environment [Bilthoven] (RIVM), Hellenic Health Foundation, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Epidemiology and Biostatistics [Imperial College London], Imperial College London, Escuela Andaluza de Salud Publica, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Hospitales Universitarios de Granada/Universidad de Granada, CIBER de Epidemiología y Salud Pública (CIBERESP), Danish Cancer Society Research Center, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Saarland Cancer Registry, National Institute for Health and Welfare [Helsinki], The University of Western Australia (UWA), University of California [San Francisco] (UCSF), University of California, Harvard T.H. Chan School of Public Health, Cancer Registry of Norway, Institute of Population-based Cancer Research, University of Oslo (UiO), National Cancer Center, Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], University of Melbourne-Melbourne School for Population and Global Health, Queensland Brain Institute, University of Queensland [Brisbane], London School of Hygiene and Tropical Medicine (LSHTM), Skane University Hospital [Lund], University of Hawai'i [Honolulu] (UH), Keck School of Medicine [Los Angeles], University of Southern California (USC), Cancer Prevention Program, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), SWOG Southwest Oncology Group, University of Bristol [Bristol], Nuffield Department of Surgery, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota [Twin Cities] (UMN), Melbourne School for Population and Global Health-University of Melbourne, Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Cancer Research UK [C8221/A19170]

Subjects
Male, 0301 basic medicine, Oncology, 1,25-dihydroxyvitamin D, Aging, Cancer Research, MESH: Risk Assessment/methods, MESH: Prostatic Neoplasms/etiology, Disease, Prostate cancer, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Odds Ratio, Prospective Studies, Vitamin D, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Cancer, MESH: Aged, MESH: Middle Aged, Prostate Cancer, Middle Aged, 25-hydroxyvitamin D, MESH: Case-Control Studies, 3. Good health, d metabolites, Centre for Surgical Research, 030220 oncology & carcinogenesis, ICEP, pooled analysis, Risk assessment, Life Sciences & Biomedicine, Urologic Diseases, medicine.medical_specialty, Clinical Trials and Supportive Activities, Oncology and Carcinogenesis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Article, vitamin D deficiency, 03 medical and health sciences, MESH: Cross-Sectional Studies, serum 25-hydroxyvitamin d, Clinical Research, subsequent development, Internal medicine, 1,25-DIHYDROXYVITAMIN-D, medicine, Vitamin D and neurology, Journal Article, Humans, Oncology & Carcinogenesis, MESH: Vitamin D/blood, Aged, Nutrition, Science & Technology, MESH: Humans, business.industry, Prevention, Case-control study, Prostatic Neoplasms, Odds ratio, medicine.disease, MESH: Male, MESH: Odds Ratio, MESH: Prospective Studies, Cross-Sectional Studies, 030104 developmental biology, 1,25-dihydroxivatmin-d, Case-Control Studies, MESH: Vitamin D/analogs & derivatives, MESH: Prostatic Neoplasms/blood, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, polymorphisms, 1112 Oncology And Carcinogenesis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13–1.31; P trend < 0.001). However, this association varied by disease aggressiveness (Pheterogeneity = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13–1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78–1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. Significance: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.

Published
2019
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14. Development and performance evaluation of a GIS-based metric to assess exposure to airborne pollutant emissions from industrial sources

Author

Elodie Faure, Thomas Coudon, Francesca Mancini, Pietro Salizzoni, Aurélie M N Danjou, Gianluca Severi, Delphine Praud, Béatrice Fervers, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Cancer Epidemiology Centre, Cancer Council Victoria, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de Mecanique des Fluides et d'Acoustique (LMFA), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Coefficient of determination, Geographic information system, Health, Toxicology and Mutagenesis, Breast Neoplasms, 010501 environmental sciences, Dioxins, 01 natural sciences, Dispersion modelling, lcsh:RC963-969, 03 medical and health sciences, 0302 clinical medicine, Cohen's kappa, Air Pollution, Statistics, Humans, Industry, Statistical dispersion, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Cancer, 0105 earth and related environmental sciences, Exposure assessment, Air Pollutants, SIRANE, [SDE.IE]Environmental Sciences/Environmental Engineering, business.industry, lcsh:Public aspects of medicine, Methodology, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Atmospheric dispersion modeling, GIS, Emission intensity, 13. Climate action, Case-Control Studies, Geographic Information Systems, lcsh:Industrial medicine. Industrial hygiene, Environmental science, Female, France, Metric (unit), business, Environmental Monitoring, Cadmium
Abstract

Background Dioxins are environmental and persistent organic carcinogens with endocrine disrupting properties. A positive association with several cancers, including risk of breast cancer has been suggested. Objectives This study aimed to develop and assess performances of an exposure metric based on a Geographic Information System (GIS) through comparison with a validated dispersion model to estimate historical industrial dioxin exposure for its use in a case-control study nested within a prospective cohort. Methods Industrial dioxin sources were inventoried over the whole French territory (n > 2500) and annual average releases were estimated between 1990 and 2008. In three selected areas (rural, urban and urban-costal), dioxin dispersion was modelled using SIRANE, an urban Gaussian model and exposure of the French E3N cohort participants was estimated. The GIS-based metric was developed, calibrated and compared to SIRANE results using a set of parameters (local meteorological data, characteristics of industrial sources, e.g. emission intensity and stack height), by calculating weighted kappa statistics (wκ) and coefficient of determination (R2). Furthermore, as performance evaluation, the final GIS-based metric was tested to assess atmospheric exposure to cadmium. Results The concordance between the GIS-based metric and the dispersion model for dioxin exposure estimate was strong (wκ median = 0.78 (1st quintile = 0.72, 3rd quintile =0.82) and R2 median = 0.82 (1st quintile = 0.71, 3rd quintile = 0.87)). We observed similar performance for cadmium. Conclusions Our study demonstrated the ability of the GIS-based metric to reliably characterize long-term environmental dioxin and cadmium exposures as well as the pertinence of using dispersion modelling to construct and calibrate the GIS-based metric. Electronic supplementary material The online version of this article (10.1186/s12940-019-0446-x) contains supplementary material, which is available to authorized users.

Published
2019
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15. The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Author

Figlioli, G., Bogliolo, M., Catucci, I., Caleca, L., Lasheras, S. V., Pujol, R., Kiiski, J. I., Muranen, T. A., Barnes, D. R., Dennis, J., Michailidou, K., Bolla, M. K., Leslie, G., Aalfs, C. M., Balleine, R., Baxter, R., Braye, S., Carpenter, J., Dahlstrom, J., Forbes, J., Lee, C. S., Marsh, D., Morey, A., Pathmanathan, N., Scott, R., Simpson, P., Spigelman, A., Wilcken, N., Yip, D., Zeps, N., Adank, M. A., Adlard, J., Agata, S., Cadoo, K., Agnarsson, B. A., Ahearn, T., Aittomaki, K., Ambrosone, C. B., Andrews, L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Arnold, N., Aronson, K. J., Arun, B. K., Asseryanis, E., Auber, B., Auvinen, P., Azzollini, J., Balmana, J., Barkardottir, R. B., Barrowdale, D., Barwell, J., Beane Freeman, L. E., Beauparlant, C. J., Beckmann, M. W., Behrens, S., Benitez, J., Berger, R., Bermisheva, M., Blanco, A. M., Blomqvist, C., Bogdanova, N. V., Bojesen, A., Bojesen, S. E., Bonanni, B., Borg, A., Brady, A. F., Brauch, H., Brenner, H., Bruning, T., Burwinkel, B., Buys, S. S., Caldes, T., Caliebe, A., Caligo, M. A., Campa, D., Campbell, I. G., Canzian, F., Castelao, J. E., Chang-Claude, J., Chanock, S. J., Claes, K. B. M., Clarke, C. L., Collavoli, A., Conner, T. A., Cox, D. G., Cybulski, C., Czene, K., Daly, M. B., de la Hoya, M., Devilee, P., Diez, O., Ding, Y. C., Dite, G. S., Ditsch, N., Domchek, S. M., Dorfling, C. M., dos-Santos-Silva, I., Durda, K., Dwek, M., Eccles, D. M., Ekici, A. B., Eliassen, A. H., Ellberg, C., Eriksson, M., Evans, D. G., Fasching, P. A., Figueroa, J., Flyger, H., Foulkes, W. D., Friebel, T. M., Friedman, E., Gabrielson, M., Gaddam, P., Gago-Dominguez, M., Gao, C., Gapstur, S. M., Garber, J., Garcia-Closas, M., Garcia-Saenz, J. A., Gaudet, M. M., Gayther, S. A., Belotti, M., Bertrand, O., Birot, A. -M., Buecher, B., Caputo, S., Dupre, A., Fourme, E., Gauthier-Villars, M., Golmard, L., Le Mentec, M., Moncoutier, V., de Pauw, A., Saule, C., Boutry-Kryza, N., Calender, A., Giraud, S., Leone, M., Bressac-de-Paillerets, B., Caron, O., Guillaud-Bataille, M., Bignon, Y. -J., Uhrhammer, N., Bonadona, V., Lasset, C., Berthet, P., Castera, L., Vaur, D., Bourdon, V., Nogues, C., Noguchi, T., Popovici, C., Remenieras, A., Sobol, H., Coupier, I., Pujol, P., Adenis, C., Dumont, A., Revillion, F., Muller, D., Barouk-Simonet, E., Bonnet, F., Bubien, V., Longy, M., Sevenet, N., Gladieff, L., Guimbaud, R., Feillel, V., Toulas, C., Dreyfus, H., Leroux, C. D., Peysselon, M., Rebischung, C., Legrand, C., Baurand, A., Bertolone, G., Coron, F., Faivre, L., Jacquot, C., Lizard, S., Kientz, C., Lebrun, M., Prieur, F., Fert-Ferrer, S., Mari, V., Venat-Bouvet, L., Bezieau, S., Delnatte, C., Mortemousque, I., Colas, C., Coulet, F., Soubrier, F., Warcoin, M., Bronner, M., Sokolowska, J., Collonge-Rame, M. -A., Damette, A., Gesta, P., Lallaoui, H., Chiesa, J., Molina-Gomes, D., Ingster, O., Manouvrier-Hanu, S., Lejeune, S., Giles, G. G., Glendon, G., Godwin, A. K., Goldberg, M. S., Goldgar, D. E., Guenel, P., Gutierrez-Barrera, A. M., Haeberle, L., Haiman, C. A., Hakansson, N., Hall, P., Hamann, U., Harrington, P. A., Hein, A., Heyworth, J., Hillemanns, P., Hollestelle, A., Hopper, J. L., Hosgood, H. D., Howell, A., Hu, C., Hulick, P. J., Hunter, D. J., Imyanitov, E. N., Aghmesheh, M., Greening, S., Amor, D., Gattas, M., Botes, L., Buckley, M., Friedlander, M., Koehler, J., Meiser, B., Saleh, M., Salisbury, E., Trainer, A., Tucker, K., Antill, Y., Dobrovic, A., Fellows, A., Fox, S., Harris, M., Nightingale, S., Phillips, K., Sambrook, J., Thorne, H., Armitage, S., Arnold, L., Kefford, R., Kirk, J., Rickard, E., Bastick, P., Beesley, J., Hayward, N., Spurdle, A., Walker, L., Beilby, J., Saunders, C., Bennett, I., Blackburn, A., Bogwitz, M., Gaff, C., Lindeman, G., Pachter, N., Scott, C., Sexton, A., Visvader, J., Taylor, J., Winship, I., Brennan, M., Brown, M., French, J., Edwards, S., Burgess, M., Burke, J., Patterson, B., Butow, P., Culling, B., Caldon, L., Callen, D., Chauhan, D., Eisenbruch, M., Heiniger, L., Chauhan, M., Christian, A., Dixon, J., Kidd, A., Cohen, P., Colley, A., Fenton, G., Crook, A., Dickson, R., Field, M., Cui, J., Cummings, M., Dawson, S. -J., Defazio, A., Delatycki, M., Dudding, T., Edkins, T., Farshid, G., Flanagan, J., Fong, P., Forrest, L., Gallego-Ortega, D., George, P., Gill, G., Kollias, J., Haan, E., Hart, S., Jenkins, M., Hunt, C., Lakhani, S., Lipton, L., Lobb, L., Mann, G., Mclachlan, S. A., O'Connell, S., O'Sullivan, S., Pieper, E., Robinson, B., Saunus, J., Scott, E., Shelling, A., Williams, R., Young, M. A., Isaacs, C., Jakimovska, M., Jakubowska, A., James, P., Janavicius, R., Janni, W., John, E. M., Jones, M. E., Jung, A., Kaaks, R., Karlan, B. Y., Khusnutdinova, E., Kitahara, C. M., Konstantopoulou, I., Koutros, S., Kraft, P., Lambrechts, D., Lazaro, C., Le Marchand, L., Lester, J., Lesueur, F., Lilyquist, J., Loud, J. T., K. H., Lu, Luben, R. N., Lubinski, J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martens, J. W. M., Maurer, T., Mavroudis, D., Mebirouk, N., Meindl, A., Menon, U., Miller, A., Montagna, M., Nathanson, K. L., Neuhausen, S. L., Newman, W. G., Nguyen-Dumont, T., Nielsen, F. C., Nielsen, S., Nikitina-Zake, L., Offit, K., Olah, E., Olopade, O. I., Olshan, A. F., Olson, J. E., Olsson, H., Osorio, A., Ottini, L., Peissel, B., Peixoto, A., Peto, J., Plaseska-Karanfilska, D., Pocza, T., Presneau, N., Pujana, M. A., Punie, K., Rack, B., Rantala, J., Rashid, M. U., Rau-Murthy, R., Rennert, G., Lejbkowicz, F., Rhenius, V., Romero, A., Rookus, M. A., Ross, E. A., Rossing, M., Rudaitis, V., Ruebner, M., Saloustros, E., Sanden, K., Santamarina, M., Scheuner, M. T., Schmutzler, R. K., Schneider, M., Senter, L., Shah, M., Sharma, P., Shu, X. -O., Simard, J., Singer, C. F., Sohn, C., Soucy, P., Southey, M. C., Spinelli, J. J., Steele, L., Stoppa-Lyonnet, D., Tapper, W. J., Teixeira, M. R., Terry, M. B., Thomassen, M., Thompson, J., Thull, D. L., Tischkowitz, M., Tollenaar, R. A. E. M., Torres, D., Troester, M. A., Truong, T., Tung, N., Untch, M., Vachon, C. M., van Rensburg, E. J., van Veen, E. M., Vega, A., Viel, A., Wappenschmidt, B., Weitzel, J. N., Wendt, C., Wieme, G., Wolk, A., Yang, X. R., Zheng, W., Ziogas, A., Zorn, K. K., Dunning, A. M., Lush, M., Wang, Q., Mcguffog, L., Parsons, M. T., Pharoah, P. D. P., Fostira, F., Toland, A. E., Andrulis, I. L., Ramus, S. J., Swerdlow, A. J., Greene, M. H., Chung, W. K., Milne, R. L., Chenevix-Trench, G., Dork, T., Schmidt, M. K., Easton, D. F., Radice, P., Hahnen, E., Antoniou, A. C., Couch, F. J., Nevanlinna, H., Surralles, J., Peterlongo, P., Caleca, Laura [0000-0002-3381-7493], Muranen, Taru A. [0000-0002-5895-1808], Dennis, Joe [0000-0003-4591-1214], Adlard, Julian [0000-0002-1693-0435], Arndt, Volker [0000-0001-9320-8684], Auber, Bernd [0000-0003-1880-291X], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Devilee, Peter [0000-0002-8023-2009], Foulkes, William D. [0000-0001-7427-4651], Isaacs, Claudine [0000-0002-9646-1260], Jakimovska, Milena [0000-0002-1506-0669], Konstantopoulou, Irene [0000-0002-0470-0309], Lesueur, Fabienne [0000-0001-7404-4549], Menon, Usha [0000-0003-3708-1732], Miller, Austin [0000-0001-9739-8462], Peto, Julian [0000-0002-1685-8912], Punie, Kevin [0000-0002-1162-7963], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher [0000-0003-1340-0647], Viel, Alessandra [0000-0003-2804-0840], Wieme, Greet [0000-0003-2718-5300], Zheng, Wei [0000-0003-1226-070X], Ziogas, Argyrios [0000-0003-4529-3727], Greene, Mark H. [0000-0003-1852-9239], Nevanlinna, Heli [0000-0002-0916-2976], Peterlongo, Paolo [0000-0001-6951-6855], Apollo - University of Cambridge Repository, Medical Oncology, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona (UAB), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Clinical Genetics, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Yorkshire Regional Genetics Service, Department of Pathology, University Hospital and University of Iceland School of Medicine, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, Università degli Studi di Milano [Milano] (UNIMI), Medical Oncology Department, Vall d'Hebron University Hospital [Barcelona], University of Iceland [Reykjavik]-Landspitali - University Hospital, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Leicestershire Clinical Genetics Service, University Hospitals Leicester, Occupational and Environmental Epidemiology Branch [Bethesda, Maryland], Division of Cancer Epidemiology and Genetics [Bethesda, Maryland], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Chaim Sheba Medical Center, Institute of Biochemistry and Genetics of Ufa Scientific Centre, Russian Academy of Sciences [Moscow] (RAS), Department of Oncology, Department of Obstetrics and Gynaecology (MHH), Hannover Medical School [Hannover] (MHH), Division of Cancer Prevention and Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, North West Thames Regional Genetics, Northwick Park Hospital, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart], Division of Clinical Epidemiology and Aging Research, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Molecular Epidemiology Research Group, Department of Internal Medicine, Huntsman Cancer Institute, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Cancer Epidemiology, Division of Cancer Epidemiology, Division of Cancer Epidemiology and Genetics, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Division of Population Science, Fox Chase Cancer Center, Department of Human Genetics & Department of Pathology, Leiden University Medical Center (LUMC), Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Department of Obstetrics and Gynecology [Munich, Germany], University-Hospital Munich-Großhadern [München]-Ludwig Maximilian University [Munich] (LMU), Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Wessex clinical genetics service, Lund University Hospital, Department of Genomic Medicine, University of Manchester [Manchester], Department of Breast Surgery, Herlev and Gentofte Hospital, Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, National Institutes of Health [Bethesda] (NIH), Epidemiology Research Program, American Cancer Society, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), University of Melbourne, Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Kansas City, KS, USA], International Agency for Cancer Research (IACR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of OB/Gyn, University Breast Center Franconia, Univeristy Hospital Erlangen, Molecular Genetics of Breast Cancer, Centre for Cancer Genetic Epidemiology [Cambridge], University of Cambridge [UK] (CAM)-Department of Oncology, Department of Medical Oncology, Josephine Nefkens Institute and Daniel den Hoed Cancer Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, The Christie, Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion, Vilnius University [Vilnius]-Hospital Santariskiu Clinics, Department of Gynecology and Obstetrics, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Department of Epidemiology, Cancer Prevention Institute of California, Unit of Nutrition and Cancer, Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Institute of Biochemistry and Genetics [Bashkortostan Republic, Russia], Russian Academy of Sciences / Ufa Scientific Centre [Bashkortostan Republic, Russia]], National Center for Scientific Research 'Demokritos' (NCSR), Harvard School of Public Health, Laboratory for translational genetics Leuven, Genetic Counseling and Hereditary Cancer Programme, Catalan Institute of Oncology, University of Hawai‘i [Mānoa] (UHM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Genetics Branch, Strangeways Research Laboratory, Unit of Medical Genetics, Fondazione IRCCS INT, Department of Gynaecology and Obstetrics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institute for Women's Health [London], University College London Hospitals (UCLH), Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Department of Medicine, Medical Genetics, Abramson Cancer Center-Perelman School of Medicine, Department of Population Sciences, Beckman Research Institute of City of Hope, Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Molecular Genetics and Department of Chemotherapy, National Institute of Oncology, University of Chicago, Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human Genetics Group, Spanish National Cancer Research Centre, Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Genetics, Portuguese Oncology Institute, Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), University of Munich, Karolinska University Hospital [Stockholm], Umm Al-Qura University, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Netherlands Cancer Institute, IT University of Copenhagen (ITU), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Queen's University [Belfast] (QUB), Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University School of Medicine [Nashville], Laboratoire de Génomique des Cancers, Université Laval [Québec] (ULaval), Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, Universität Heidelberg [Heidelberg], Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Columbia University [New York], Odense University Hospital, Instituto de Genética Humana, Pontificia Universidad Javeriana (PUJ), HELIOS Hospital Berlin-Buch, Cancer Genetics Laboratory, University of Pretoria [South Africa], Genomic Medicine Group, Universidade de Santiago de Compostela [Spain] (USC ), Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, City of Hope Comprehensive Cancer Center and Department of Population Sciences, Beckman Research Institute, Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, University of Science and Technology Beijing [Beijing] (USTB), University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Université de Pau et des Pays de l'Adour (UPPA), Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, The institute of cancer research [London], Department of Medical Genetics, Mayo Clinic, Cancer Epidemiology Centre, Cancer Council Victoria, Queensland Institute of Medical Research, Cancer Research U.K. Genetic Epidemiology Unit, Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medici, Department of Laboratory Medicine and Pathology, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine-Fondazione IRCCS Istituto Nazionale Tumori (INT), Muranen, Taru A [0000-0002-5895-1808], Foulkes, William D [0000-0001-7427-4651], Greene, Mark H [0000-0003-1852-9239], Institut Català de la Salut, [Figlioli G, Catucci I] IFOM - the FIRC Institute for Molecular Oncology, Genome Diagnostics Program, Milan, Italy. [Bogliolo M, Pujol R] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain. Institute of Biomedical Research, Sant Pau Hospital, Barcelona, Spain. [Caleca L] Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Milan, Italy. [Lasheras SV] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Genètica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Hospital Universitari Vall d'Hebron, University of Iceland [Reykjavik], Università degli Studi di Milano = University of Milan (UNIMI), Universiteit Leiden-Universiteit Leiden, University of Pennsylvania-University of Pennsylvania, University of Pennsylvania, Georgetown University [Washington] (GU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universität Heidelberg [Heidelberg] = Heidelberg University, European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), Human Genetics, Vall d'Hebron Barcelona Hospital Campus, Autonomous University of Barcelona, Universitat Autònoma de Barcelona [Barcelona] (UAB), Università degli studi di Milano [Milano], University Hospitals of Leicester, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Biology, University of Pisa, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pomeranian Medical University-International Hereditary Cancer Centre, McGill University, University of Kansas Medical Center [Lawrence], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Oncology-University of Cambridge [UK] (CAM), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Technical University of Munich (TUM), Università degli Studi di Roma 'La Sapienza' [Rome], IT University of Copenhagen, Laval University [Québec], Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Pontificia Universidad Javeriana, University of Santiago de Compostela, Læknadeild (HÍ), Faculty of Medicine (UI), Biomedical Center (UI), Lífvísindasetur (HÍ), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), MINES ParisTech - École nationale supérieure des mines de Paris, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Universidade do Porto, Ministerio de Economía y Competitividad (España), Unión Europea. Comisión Europea, Against Breast Cancer, Cancer Research UK (Reino Unido), Unión Europea. Comisión Europea. H2020, Cancer UK Grant, Canadian Institutes of Health Research, Ministère de Économie, de la science et de innovation (Canadá), NIH - National Cancer Institute (NCI) (Estados Unidos), Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Xunta de Galicia (España), Canadian Cancer Society, California Breast Cancer Research Program, California Department of Public Health, Medical Research Council (Reino Unido), Free State of Saxony, Germany (LIFE -Leipzig Research Centre for Civilization Diseases), Federal Ministry of Education & Research (Alemania), German Cancer Aid, Helsinki University Central Hospital Research Fund, Finlands Akademi (Finlandia), Deutsche Forschungsgemeinschaft (Alemania), Russian Foundation for Basic Research, Ministry of Science and Higher Education (Rusia), National Health and Medical Research Council (Australia), Biobanking and BioMolecular resources Research Infrastructure (Países Bajos), Estée Lauder Companies’ Breast Cancer Campaign, Swedish Research Council, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Lon V. Smith Foundation, Research Coincil of Lithuania, Italian Association for Cancer Research, University of Kansas. Cancer Center (Estados Unidos), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), French National Cancer Institute, Netherlands Organisation for Health Research and Development, Pink Ribbons Project, United States of Department of Health & Human Services, HUS Gynecology and Obstetrics, Clinicum, University of Helsinki, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, University Management, HUS Comprehensive Cancer Center, Biosciences, Helsinki University Hospital, and Lietuvos Mokslo Taryba (Lituania)

Subjects
0301 basic medicine, Gene mutation, Càncer - Aspectes genètics, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Mama - Càncer, Fanconi anemia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Brjóstakrabbamein, Medicine and Health Sciences, Pharmacology (medical), FANCM, 631/208/68, skin and connective tissue diseases, Cancer genetics, Triple-negative breast cancer, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Manchester Cancer Research Centre, Otros calificadores::Otros calificadores::/genética [Otros calificadores], article, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Life Sciences & Biomedicine, 3122 Cancers, ABCTB Investigators, lcsh:RC254-282, KConFab, Olaparib, Càncer de mama, GEMO Study Collaborators, 03 medical and health sciences, breast cancer, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, SDG 3 - Good Health and Well-being, 631/67/68, medicine, Other subheadings::Other subheadings::/genetics [Other subheadings], Erfðafræði, Radiology, Nuclear Medicine and imaging, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ddc:610, Risk factor, CHEK2, Krabbamein, Cancer och onkologi, FancM, Science & Technology, cancer, MUTATIONS, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Biology and Life Sciences, nutritional and metabolic diseases, cancer genetics, medicine.disease, GENE, Expressió gènica, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES], 030104 developmental biology, chemistry, 692/4028/67/68, Cancer and Oncology, FANCONI-ANEMIA, Cancer research, gene expression, C.5791C-GREATER-THAN-T, business
Abstract

Publisher's version (útgefin grein), Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors., Peterlongo laboratory is supported by Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo and by a fellowship from Fondazione Umberto Veronesi to G. Figlioli. Surrallés laboratory is supported by the ICREA-Academia program, the Spanish Ministry of Health (projects FANCOSTEM and FANCOLEN), the Spanish Ministry of Economy and Competiveness (projects CB06/07/0023 and RTI2018-098419-B-I00), the European Commission (EUROFANCOLEN project HEALTH-F5-2012-305421 and P-SPHERE COFUND project), the Fanconi Anemia Research Fund Inc, and the “Fondo Europeo de Desarrollo Regional, una manera de hacer Europa” (FEDER). CIBERER is an initiative of the Instituto de Salud Carlos III, Spain. BCAC: we thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. ABCFS thank Maggie Angelakos, Judi Maskiell, Tu Nguyen-Dumont is a National Breast Cancer Foundation (Australia) Career Development Fellow. ABCS thanks the Blood bank Sanquin, The Netherlands. Samples are made available to researchers on a non-exclusive basis. BCEES thanks Allyson Thomson, Christobel Saunders, Terry Slevin, BreastScreen Western Australia, Elizabeth Wylie, Rachel Lloyd. The BCINIS study would not have been possible without the contributions of Dr. Hedy Rennert, Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet of the NICCC in Haifa, and all the contributing family medicine, surgery, pathology and oncology teams in all medical institutes in Northern Israel. The BREOGAN study would not have been possible without the contributions of the following: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Muñoz Garzón, Alejandro Novo Domínguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Peña Fernández, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), José Antúnez, Máximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigación Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquín González-Carreró and the staff of the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS, Vigo, Spain. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. CBCS thanks study participants, co-investigators, collaborators and staff of the Canadian Breast Cancer Study, and project coordinators Agnes Lai and Celine Morissette. CCGP thanks Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgård Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. Investigators from the CPS-II cohort thank the participants and Study Management Group for their invaluable contributions to this research. They also acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, as well as cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, and Eunjung Lee at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine, and Fred Schumacher at Case Western University. DIETCOMPLYF thanks the patients, nurses and clinical staff involved in the study. The DietCompLyf study was funded by the charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER thanks Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. FHRISK thanks NIHR for funding. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Kröber and LIFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nüchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany [HB, Wing-Yee Lo], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [HB], Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2180 - 390900677 [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [TB, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS thanks Michael Bremer. HEBCS thanks Heidi Toiminen, Kristiina Aittomäki, Irja Erkkilä and Outi Malkavaara. HMBCS thanks Peter Hillemanns, Hans Christiansen and Johann H. Karstens. HUBCS thanks Shamil Gantsev. KARMA thanks the Swedish Medical Research Counsel. KBCP thanks Eija Myöhänen, Helena Kemiläinen. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MABCS thanks Milena Jakimovska (RCGEB “Georgi D. Efremov), Katerina Kubelka, Mitko Karadjozov (Adzibadem-Sistina” Hospital), Andrej Arsovski and Liljana Stojanovska (Re-Medika” Hospital) for their contributions and commitment to this study. MARIE thanks Petra Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. MBCSG (Milan Breast Cancer Study Group) thanks Daniela Zaffaroni, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. We thank the coordinators, the research staff and especially the MMHS participants for their continued collaboration on research studies in breast cancer. MSKCC thanks Marina Corines and Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Québec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skillful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. NBHS thanks study participants and research staff for their contributions and commitment to the studies. We would like to thank the participants and staff of the Nurses’ Health Study and Nurses’ Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The study protocol was approved by the institutional review boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander and Nayana Weerasooriya. ORIGO thanks E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. PBCS thanks Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao and Michael Stagner. The ethical approval for the POSH study is MREC /00/6/69, UKCRN ID: 1137. We thank staff in the Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. PREFACE thanks Sonja Oeser and Silke Landrith. PROCAS thanks NIHR for funding. RBCS thanks Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. We thank the SEARCH and EPIC teams. SKKDKFZS thanks all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. We thank the SUCCESS Study teams in Munich, Duessldorf, Erlangen and Ulm. SZBCS thanks Ewa Putresza. UCIBCS thanks Irene Masunaka. UKBGS thanks Breast Cancer Now and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. CIMBA: we are grateful to all the families and clinicians who contribute to the studies; Sue Healey, in particular taking on the task of mutation classification with the late Olga Sinilnikova; Maggie Angelakos, Judi Maskiell, Helen Tsimiklis; members and participants in the New York site of the Breast Cancer Family Registry; members and participants in the Ontario Familial Breast Cancer Registry; Vilius Rudaitis and Laimonas Griškevičius; Yuan Chun Ding and Linda Steele for their work in participant enrollment and biospecimen and data management; Bent Ejlertsen and Anne-Marie Gerdes for the recruitment and genetic counseling of participants; Alicia Barroso, Rosario Alonso and Guillermo Pita; all the individuals and the researchers who took part in CONSIT TEAM (Consorzio Italiano Tumori Ereditari Alla Mammella), thanks in particular: Giulia Cagnoli, Roberta Villa, Irene Feroce, Mariarosaria Calvello, Riccardo Dolcetti, Giuseppe Giannini, Laura Papi, Gabriele Lorenzo Capone, Liliana Varesco, Viviana Gismondi, Maria Grazia Tibiletti, Daniela Furlan, Antonella Savarese, Aline Martayan, Stefania Tommasi, Brunella Pilato, Isabella Marchi, Elena Bandieri, Antonio Russo, Daniele Calistri and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy. FPGMX: members of the Cancer Genetics group (IDIS): Ana Blanco, Miguel Aguado, Uxía Esperón and Belinda Rodríguez. We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan (Noor Muhammad, Sidra Gull, Seerat Bajwa, Faiz Ali Khan, Humaira Naeemi, Saima Faisal, Asif Loya, Mohammed Aasim Yusuf) and Bogota, Colombia (Diana Torres, Ignacio Briceno, Fabian Gil). Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study is a study from the National Cancer Genetics Network UNICANCER Genetic Group, France. We wish to pay a tribute to Olga M. Sinilnikova, who with Dominique Stoppa-Lyonnet initiated and coordinated GEMO until she sadly passed away on the 30th June 2014. The team in Lyon (Olga Sinilnikova, Mélanie Léoné, Laure Barjhoux, Carole Verny-Pierre, Sylvie Mazoyer, Francesca Damiola, Valérie Sornin) managed the GEMO samples until the biological resource centre was transferred to Paris in December 2015 (Noura Mebirouk, Fabienne Lesueur, Dominique Stoppa-Lyonnet). We want to thank all the GEMO collaborating groups for their contribution to this study. Drs.Sofia Khan, Irja Erkkilä and Virpi Palola; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collée, A.M.W. van den Ouweland, M.J. Hooning, C.M. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, M.J. Koudijs; Amsterdam Medical Center, NL: C.M. Aalfs, H.E.J. Meijers-Heijboer; VU University Medical Center, Amsterdam, NL: K. van Engelen, J.J.P. Gille; Maastricht University Medical Center, NL: E.B. Gómez-Garcia, M.J. Blok; University of Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Comprehensive Cancer Organisation (IKNL): S. Siesling, J.Verloop; The nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA): A.W. van den Belt-Dusebout. HEBON thanks the study participants and the registration teams of IKNL and PALGA for part of the data collection. Overbeek; the Hungarian Breast and Ovarian Cancer Study Group members (Janos Papp, Aniko Bozsik, Zoltan Matrai, Miklos Kasler, Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary) and the clinicians and patients for their contributions to this study; HVH (University Hospital Vall d’Hebron) the authors acknowledge the Oncogenetics Group (VHIO) and the High Risk and Cancer Prevention Unit of the University Hospital Vall d’Hebron, Miguel Servet Progam (CP10/00617), and the Cellex Foundation for providing research facilities and equipment; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; Dr Martine Dumont for sample management and skillful assistance; Catarina Santos and Pedro Pinto; members of the Center of Molecular Diagnosis, Oncogenetics Department and Molecular Oncology Research Center of Barretos Cancer Hospital; Heather Thorne, Eveline Niedermayr, all the kConFab investigators, research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab; the investigators of the Australia New Zealand NRG Oncology group; members and participants in the Ontario Cancer Genetics Network; Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O’Conor; Christina Selkirk; Helena Jernström, Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from Gothenburg Sahlgrenska University Hospital: Anna Öfverholm, Margareta Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska University Hospital: Anna von Wachenfeldt, Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza; from Umeå University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor, Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta Hellström Pigg, Richard Rosenquist; from Linköping University Hospital: Marie Stenmark-Askmalm, Sigrun Liedgren; Cecilia Zvocec, Qun Niu; Joyce Seldon and Lorna Kwan; Dr. Robert Nussbaum, Beth Crawford, Kate Loranger, Julie Mak, Nicola Stewart, Robin Lee, Amie Blanco and Peggy Conrad and Salina Chan; Carole Pye, Patricia Harrington and Eva Wozniak. OSUCCG thanks Kevin Sweet, Caroline Craven, Julia Cooper, Michelle O’Conor and Amber Aeilts. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union’s Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de l’Économie, Science et Innovation du Québec through Genome Québec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia. For the BCFR-NY, BCFR-PA, BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BCINIS study was funded by the BCRF (The Breast Cancer Research Foundation, USA). The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l’Alimentation, de l’Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, K05 CA136967, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the German Research Foundation (Do 761/10-1). The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014 and 17-44-020498. E.K was supported by the program for support the bioresource collections №007-030164/2 and study was performed as part of the assignment of the Ministry of Science and Higher Education of Russian Federation (№АААА-А16-116020350032-1). Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. LMBC is supported by the ‘Stichting tegen Kanker’. DL is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov” and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects “5 × 1000”). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council [grant 2017-00644 for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER)]. The SZBCS is financially supported under the program of Minister of Science and Higher Education “Regional Initiative of Excellence” in years 2019-2022, Grant No 002/RID/2018/19. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. CIMBA CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015 and Nr. P-MIP-19-164. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Funds from Italian citizens who allocated the 5 × 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5 × 1000’) to S. Manoukian. UNIROMA1: Italian Association for Cancer Research (AIRC; grant no. 21389) to L. Ottini. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: NIH/NCI grant P30-CA006927. The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. Ana Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigación Biomédica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program, the French National Institute of Cancer (INCa) (grants AOR 01 082, 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015) and the Fondation ARC pour la recherche sur le cancer (grant PJA 20151203365). GEORGETOWN: the Survey, Recruitment and Biospecimen Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008) and the Fisher Center for Hereditary Cancer and Clinical Genomics Research. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI_OTKA K-112228. HVH (University Hospital Vall d’Hebron) This work was supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds: FIS PI12/02585 and PI15/00355. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563, P18/01029, and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338, 2017SGR449, and PERIS Project MedPerCan), and CERCA program. IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and “5 × 1000” Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-45012). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: was funded by the Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women’s Cancer Research Alliance and the Breast Cancer research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Researc h UK. UPENN: National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124.

Published
2019
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16. Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort

Author

Roel Vermeulen, J. Ramón Quirós, Torkjel M. Sandanger, Domenico Palli, Carlotta Sacerdote, Gianluca Severi, Eva Ardanaz, Bas Bueno-de-Mesquita, Sara Grioni, Malin Sund, Rudolf Kaaks, Manuela M. Bergmann, Matthias B. Schulze, Federico Canzian, Miguel Rodríguez-Barranco, Luca Morelli, Carlo La Vecchia, Pietro Ferrari, Salvatore Panico, Anna Karakatsani, Theron Johnson, Pilar Amiano, Kay-Tee Khaw, Nicholas J. Wareham, Paula Jakszyn, Sandra Colorado-Yohar, Daniele Campa, Marie-Christine Boutron-Ruault, Julie A. Schmidt, Rosario Tumino, Anne Tjønneland, Verena Katzke, Vittorio Perduca, Manuel Gentiluomo, Antonia Trichopoulou, Elisabete Weiderpass, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Danish Cancer Society, Cancer Epidemiology Centre, Cancer Council Victoria, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Department of Community Medicine, Faculty of Health Sciences, The Arctic University of Norway (UiT), Nutrition and Metabolism Section, International Agency for Research on Cancer, Deutsches Krebsforschungszentrum, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Dept of Epidemiology, WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Hellenic Health Foundation, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), Istituto per lo Studio e la Prevezione Oncologica, Partenaires INRAE, Epidemiology, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Civile - M.P.Arezzo Hospital, CPO Piemonte, Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Division of Environmental Epidemiology, Utrecht University [Utrecht]-Institute of Risk Assessment Sciences, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Surgery and Perioperative Sciences, Umea University Hospital, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, L´Hospitallet de Llobregat, Department of Pathology, Santa Chiara Hospital, Department of Cancer Epidemiology, One Health Chemisch, dIRAS RA-2, Gentiluomo, Manuel [0000-0002-0366-9653], Katzke, Verena A [0000-0002-6509-6555], Tjønneland, Anne [0000-0003-4385-2097], Perduca, Vittorio [0000-0003-0339-0473], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Weiderpass, Elisabete [0000-0003-2237-0128], Johnson, Theron [0000-0003-4850-282X], Bergmann, Manuela [0000-0001-5064-227X], Karakatsani, Anna [0000-0002-3275-2026], La Vecchia, Carlo [0000-0003-1441-897X], Palli, Domenico [0000-0002-5558-2437], Grioni, Sara [0000-0002-5891-8426], Tumino, Rosario [0000-0003-2666-414X], Ardanaz, Eva [0000-0001-8434-2013], Schmidt, Julie A [0000-0002-7733-8750], Morelli, Luca [0000-0002-7742-9556], Canzian, Federico [0000-0002-4261-4583], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Mitochondrial DNA, Pancreatic ductal adenocarcinoma, DNA Copy Number Variations, Epidemiology, EPIC, Real-Time Polymerase Chain Reaction, DNA, Mitochondrial, Risk Assessment, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Pancreatic cancer, medicine, Biomarkers, Tumor, Leukocytes, Humans, Copy-number variation, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, 2. Zero hunger, business.industry, Incidence, Age Factors, Middle Aged, Protective Factors, medicine.disease, Peripheral blood, 3. Good health, Mitochondria, Europe, Pancreatic Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, Case-Control Studies, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, business
Abstract

Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited. Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results: We observed lower mtDNA copy number with advancing age (P = 6.54 × 10−5) and with a high body mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.16–0.79; P = 0.01] when comparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 (95% CI, 0.07–0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses. Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk. Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.

Published
2020
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17. Computational tools to detect signatures of mutational processes in DNA from tumours: a review and empirical comparison of performance

Author

Hanane Omichessan, Vittorio Perduca, Gianluca Severi, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Centre for Epidemiology and Biostatistics [Victoria, Australia], University of Melbourne-Melbourne School of Population and Global Health [Victoria, Australia], Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], University of Melbourne-Melbourne School for Population and Global Health, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Perduca, Vittorio, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
Empirical comparison, Computer science, Somatic cell, Science, DNA Mutational Analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, medicine.disease_cause, Genome, 03 medical and health sciences, chemistry.chemical_compound, Germline mutation, 0302 clinical medicine, [STAT.AP] Statistics [stat]/Applications [stat.AP], [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer genome, Neoplasms, medicine, Humans, Exome sequencing, 030304 developmental biology, [STAT.AP]Statistics [stat]/Applications [stat.AP], 0303 health sciences, Mutation, Multidisciplinary, Mutation Spectra, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], COSMIC cancer database, Genome, Human, Computational Biology, DNA, Neoplasm, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Identification (information), chemistry, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Medicine, DNA, Algorithms, Research Article
Abstract

International audience; Mutational signatures refer to patterns in the occurrence of somatic mutations that might be uniquely ascribed to particular mutational process. Tumour mutation catalogues can reveal mutational signatures but are often consistent with the mutation spectra produced by a variety of mutagens. To date, after the analysis of tens of thousands of exomes and genomes from about 40 different cancer types, tens of mutational signatures characterized by a unique probability profile across the 96 trinucleotide-based mutation types have been identified , validated and catalogued. At the same time, several concurrent methods have been developed for either the quantification of the contribution of catalogued signatures in a given cancer sequence or the identification of new signatures from a sample of cancer sequences. A review of existing computational tools has been recently published to guide researchers and practitioners through their mutational signature analyses, but other tools have been introduced since its publication and, a systematic evaluation and comparison of the performance of such tools is still lacking. In order to fill this gap, we have carried out an empirical evaluation of the main packages available to date, using both real and simulated data. Among other results, our empirical study shows that the identification of signatures is more difficult for cancers characterized by multiple signatures each having a small contribution. This work suggests that detection methods based on probabilistic models, especially EMu and bayesNMF, have in general better performance than NMF-based methods.

Published
2018
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18. The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Author

Douglas F. Easton, T.M. Mooij, Christian F. Singer, Lenka Foretova, Matti A. Rookus, Karin Kast, Kai-ren Ong, Louise Izatt, Jessica Moretta-Serra, Margreet G. E. M. Ausems, Diana Eccles, Patrick J. Morrison, Jan C. Oosterwijk, Mary B. Daly, Alex Henderson, Rita K. Schmutzler, Ana Osorio, Charlotte J. Dommering, Anne-Marie Gerdes, Marie Navratilova, Ibccs, Carole Brewer, Mieke Kriege, Mary Beth Terry, Christoph Engel, D. Gareth Evans, Edith Olah, Jackie Cook, David E. Goldgar, Anna Jakubowska, Antonis C. Antoniou, Jacques Simard, Laurence Gladieff, Catherine Noguès, Esther M. John, Brita Arver, Håkan Olsson, Jasmine A. McDonald, Irene L. Andrulis, Nadine Andrieu, Munaza Ahmed, Yen Y. Tan, Yuyan Liao, Embrace, Genepso, Bcfr, Hebon, kConFab, Trinidad Caldés, Véronique Mari, Roger L. Milne, Michael Friedlander, Elisabeth Luporsi, John L. Hopper, Marie-José Roos-Blom, Flora E. van Leeuwen, Sue-Anne McLachlan, Saundra S. Buys, Debra Frost, Daniel Barrowdale, Bruno Buecher, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Columbia University [New York], Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Service de Génétique Oncologique, Institut Curie [Paris], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Claudius Regaud, Centre Alexis Vautrin (CAV), Newcastle Upon Tyne Hospitals NHS Trust, Department of Clinical Genetics, Royal Devon & Exeter Hospital, St Mary's Hospital, Wessex Clinical Genetics Service, Princess Anne Hospital, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Northern Ireland Regional Genetics Centre, Belfast City Hospital, Department of Clinical Genetics and Human Genetics, VU University Medical Center [Amsterdam], Department of Genetics, Department of Medical Genetics, University Medical Center [Utrecht], Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Internal Medicine, Huntsman Cancer Institute, Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Epidemiology, Cancer Prevention Institute of California, Division of Population Science, Fox Chase Cancer Center, Dept of Medical Oncology, Division of Medicine, University of New South Wales [Sydney] (UNSW)-Prince of Wales Hospital Randwick, Human Genetics Group, Spanish National Cancer Research Centre, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Laboratoire de Génomique des Cancers, Université Laval [Québec] (ULaval), Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, National Institute of Oncology, Masaryk University [Brno] (MUNI), Odense University Hospital, Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Oncology, Lund University Hospital, Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, Departments of Epidemiology and Molecular Pathology, The Netherlands Cancer Institute, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Cancer Epidemiology Centre, Cancer Council Victoria, Centre for Cancer Genetic Epidemiology [Cambridge], University of Cambridge [UK] (CAM)-Department of Oncology, Netherlands Cancer Institute, Innovation et Développement dans l'Agriculture et l'Alimentation (UMR Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195), the Australian National Breast Cancer Foundation (IF 17), the National Health and Medical Research Council (454508, 288704, 145684), the US National Institute of Health (1RO1CA159868), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. MODSQUAD Czech Republic, Brno was supported by MH CZ—DRO (MMCI, 00209805) and by MEYS—NPS I - LO1413 to LF, MN. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research grants KTIA-OTKA CK80745 and NKFI OTKA K-112228 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. € Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society., European Project: 294576,EC:FP7:ERC,ERC-2011-ADG_20110310,RISK FACTORS CANCER(2012), Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), MUMC+: DA KG Lab Centraal Lab (9), Universität Leipzig [Leipzig], Institut Curie, Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, CRLCC Institut Claudius Regaud, Sheffield Children's Hospital, Birmingham Women's Hospital Healthcare NHS Trust, Pomeranian Medical University-International Hereditary Cancer Centre, Laval University [Québec], Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Innovation et Développement dans l'Agriculture et l'Agro-alimentaire (Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre national d'études agronomiques des régions chaudes (CNEARC)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Andrieu, Nadine, Genetic and environmental risk factors for common malignant tumours especially breast cancer and melanoma. - RISK FACTORS CANCER - - EC:FP7:ERC2012-04-01 - 2017-03-31 - 294576 - VALID, Medical Oncology, Pathology, Radiology & Nuclear Medicine, Columbia Mailman School of Public Health-Columbia University [New York], Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Targeted Gynaecologic Oncology (TARGON), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, INDUCED-ABORTION, endocrine system diseases, BIRTH, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, SUSCEPTIBILITY, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, [SDV.CAN] Life Sciences [q-bio]/Cancer, Medicine, COHORT, Prospective cohort study, skin and connective tissue diseases, REPRODUCTIVE FACTORS, [SDV.GEN]Life Sciences [q-bio]/Genetics, PARITY, business.industry, Proportional hazards model, Obstetrics, Hazard ratio, Retrospective cohort study, medicine.disease, CARRIERS, OVARIAN, Confidence interval, [SDV] Life Sciences [q-bio], KCONFAB, 030104 developmental biology, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Cohort, COLLABORATIVE REANALYSIS, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Breast feeding
Abstract

Background Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). Conclusions These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.

Published
2018
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19. Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study

Author

Christian F. Singer, Louise Izatt, Yen Y. Tan, Emmanuelle Mouret-Fourme, Embrace, Genepso, Bcfr, Hebon, kConFab, Marie Navratilova, Lucy Side, Trinidad Caldés, Rosemarie Davidson, Kelly-Anne Phillips, Saundra S. Buys, Dominique Leroux, Mary B. Daly, Melissa C. Southey, Marian J.E. Mourits, Brita Arver, Theo A. M. van Os, Anne-Marie Gerdes, Douglas F. Easton, Marie-José Roos-Blom, Michael Friedlander, Lieske H. Schrijver, David E. Goldgar, Anna Jakubowska, Roger L. Milne, Håkan Olsson, Lisa Walker, Ros Eeles, Flora E. van Leeuwen, Mary Porteous, Sue-Anne McLachlan, Pascaline Berthet, Lenka Foretova, Catherine Noguès, Matti A. Rookus, Debra Frost, Daniel Barrowdale, Esther M. John, Julian Adlard, Encarna B. Gomez Garcia, Nadine Andrieu, Laurence Venat-Bouvet, Anita Bane, John L. Hopper, Mary Beth Terry, Jacques Simard, Ana Osorio, Antonis C. Antoniou, Christoph Engel, Wendy K. Chung, Karin Kast, Ibccs, D. Gareth Evans, Valérie Bonadona, Edith Olah, Steve Ellis, Christi J. van Asperen, T.M. Mooij, Human Genetics, APH - Methodology, APH - Quality of Care, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Skane University Hospital [Lund], Lund University [Lund], University of Melbourne, Columbia Mailman School of Public Health, University of Utah School of Medicine [Salt Lake City], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Department of Clinical Sciences [Lund], University of Leipzig [Leipzig, Allemagne], Chapel Allerton Hospital, University of Cambridge [UK] (CAM), Queen Elizabeth University Hospital (Glasgow), Royal Marsden NHS Foundation Trust, University of Manchester [Manchester], Guy's and St Thomas NHS Foundation Trust [London], Western General Hospital [Edinburgh, UK], Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK], Churchill Hospital [Breast Care Unit], Churchill Hospital Oxford Centre for Haematology, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire [Grenoble] (CHU), hôpital couple-enfant [CHU Grenoble Alpes], Hôpital René HUGUENIN (Saint-Cloud), Hôpital Dupuytren [CHU Limoges], Huntsman Cancer Institute [Salt Lake City], University of Utah, Monash University [Melbourne], Stanford University School of Medicine [CA, USA], California Sciences Institute, Columbia University [New York], Fox Chase Cancer Center, McMaster University [Hamilton, Ontario], Karolinska Institutet [Stockholm], Leiden University Medical Center (LUMC), School for Oncology and Developmental Biology [Maastricht] (GROW), Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University Medical Center Groningen [Groningen] (UMCG), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), University of New South Wales [Sydney] (UNSW), Prince of Wales Hospital, St. Vincent's Hospital, Sydney, Medizinische Universität Wien = Medical University of Vienna, Masaryk Memorial Cancer Institute (RECAMO), University Hospital of Cologne [Cologne], Copenhagen University Hospital, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Université Laval [Québec] (ULaval), National Institute of Oncology [Budapest, Hungary], Pomeranian Medical University [Szczecin, Poland] (PMU), Spanish National Cancer Centre, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], Melbourne School for Population and Global Health-University of Melbourne, Leipzig University, Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK] (GOSHC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Masaryk Memorial Cancer Institute (MMCI), Pomeranian Medical University [Szczecin] (PUM), Mines Paris - PSL (École nationale supérieure des mines de Paris), University of Melbourne-Melbourne School for Population and Global Health, Malbec, Odile, Universiteit Leiden, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Klinische Genetica, MUMC+: DA KG Lab Centraal Lab (9), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Life Course Epidemiology (LCE), and ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Article, OVARIAN-CANCER, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, medicine, Prospective cohort study, skin and connective tissue diseases, Pregnancy, Proportional hazards model, Obstetrics, business.industry, Hazard ratio, CONSORTIUM, WOMEN, medicine.disease, PREVENTION, Confidence interval, KCONFAB, [SDV] Life Sciences [q-bio], 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, business, Cohort study
Abstract

Background For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear. Methods Breast camcer risk associations were estimated from OCP data on 6030 BRCA1 and 3809 BRCA2 mutation carriers using age-dependent Cox regression, stratified by study and birth cohort. Prospective, left-truncated retrospective and full-cohort retrospective analyses were performed. Results For BRCA1 mutation carriers, OCP use was not associated with BC risk in prospective analyses (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.75 to 1.56), but in the left-truncated and full-cohort retrospective analyses, risks were increased by 26% (95% CI = 6% to 51%) and 39% (95% CI = 23% to 58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk in prospective analyses (HR = 1.75, 95% CI = 1.03 to 2.97), but retrospective analyses were inconsistent (left-truncated: HR = 1.06, 95% CI = 0.85 to 1.33; full cohort: HR = 1.52, 95% CI = 1.28 to 1.81). There was evidence of increasing risk with duration of use, especially before the first full-term pregnancy (BRCA1: both retrospective analyses, P < .001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002). Conclusions Prospective analyses did not show that past use of OCP is associated with an increased BC risk for BRCA1 mutation carriers in young middle-aged women (40–50 years). For BRCA2 mutation carriers, a causal association is also not likely at those ages. Findings between retrospective and prospective analyses were inconsistent and could be due to survival bias or a true association for younger women who were underrepresented in the prospective cohort. Given the uncertain safety of long-term OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and nonhormonal contraceptive methods should be discussed.

Published
2018
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20. Exposure to loud noise and risk of vestibular schwannoma: results from the INTERPHONE international case?control study

Author

Deltour, Isabelle, Schlehofer, Brigitte, Massardier-Pilonchery, Amelie, Schlaefer, Klaus, Armstrong, Bruce, Giles, Graham G., Siemiatycki, Jack, Parent, Marie-Elise, Krewski, Daniel, McBride, Mary, Johansen, Christoffer, Auvinen, Anssi, Salminen, Tiina, Hours, Martine, Montestrucq, Lucile, Blettner, Maria, Berg-Beckhoff, Gabriele, Sadetzki, Siegal, Chetrit, Angela, Lagorio, Susanna, Iavarone, Ivano, Yamaguchi, Naohito, Takebayashi, Toru, Woodward, Alistair, Cook, Angus, Tynes, Tore, Klaeboe, Lars, Feychting, Maria, Lonn, Stefan, Fleming, Sarah, Swerdlow, Anthony J., Schoemaker, Minouk J., Moissonnier, Monika, Kesminiene, Ausrele, Cardis, Elisabeth, Schuz, Joachim, Vrijheid, M., Evrard, A-S, Sanchez, M., Brown, J., Nadon, L., Christensen, H. C., Kurttio, P., Lahkola, A., Bernard, M., Jarus-Hakak, A., Pearce, N., Blaasaas, K., Ahlbom, A., McKinney, Patricia A., Muir, K. R., Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Unit of Environmental Epidemiology, German Cancer Research Center, Heidelberg, Germany, parent, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), School of Public Health, The University of Sydney, Sydney, Australia, Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia, University of Montreal School of Public Health, Montreal, Canada, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Canada, and British Columbia Cancer Research Centre, British Columbia Cancer Agency, Vancouver, Canada

Subjects
Adult, Male, medicine.medical_specialty, Population, INTERNATIONAL, Audiology, NOISE, 03 medical and health sciences, 0302 clinical medicine, Occupational Exposure, Recall bias, Epidemiology, Humans, Medicine, EPIDEMIOLOGY, EXPOSURE, education, Vestibular system, education.field_of_study, ACOUSTIC NEUROMA, NOISE EXPOSURE, business.industry, Public Health, Environmental and Occupational Health, Case-control study, Neuroma, Acoustic, Odds ratio, case‒control study, Middle Aged, LOUD NOISE, 030210 environmental & occupational health, Confidence interval, VESTIBULAR SCHWANNOMA, Noise, BRUIT, CASE CONTROL STUDY, INTERPHONE, Noise, Occupational, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Public aspects of medicine, RA1-1270, business
Abstract

Objective Studies of loud noise exposure and vestibular schwannomas (VS) have shown conflicting results. The population-based INTERPHONE case‒control study was conducted in 13 countries during 2000-2004. In this paper, we report the results of analyses on the association between VS and self-reported loud noise exposure. Methods Self-reported noise exposure was analyzed in 1024 VS cases and 1984 matched controls. Life-long noise exposure was estimated through detailed questions. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using adjusted conditional logistic regression for matched sets. Results The OR for total work and leisure noise exposure was 1.6 (95% CI 1.4-1.9). OR were 1.5 (95% CI 1.3-1.9) for only occupational noise, 1.9 (95% CI 1.4-2.6) for only leisure noise and 1.7 (95% CI 1.2-2.2) for exposure in both contexts. OR increased slightly with increasing lag-time. For occupational exposures, duration, time since exposure start and a metric combining lifetime duration and weekly exposure showed significant trends of increasing risk with increasing exposure. OR did not differ markedly by source or other characteristics of noise. Conclusion The consistent associations seen are likely to reflect either recall bias or a causal association, or potentially indicate a mixture of both.

Published
2018
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21. Investigation of bias related to differences between case and control interview dates in five INTERPHONE countries

Author

Siegal Sadetzki, Alistair Woodward, Mary L. McBride, Daniel Krewski, Elisabeth Cardis, Michelle C. Turner, Lesley Richardson, Angela Chetrit, Jordi Figuerola, Graham G. Giles, Jack Siemiatycki, Bruce K. Armstrong, Rodrigo Villegas, Martine Hours, Marie-Élise Parent, Chelsea Eastman Langer, CIBER de Epidemiología y Salud Pública (CIBERESP), University of Ottawa [Ottawa], Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Chaim Sheba Medical Center, The University of Sydney, Cancer Epidemiology Centre, Cancer Council Victoria, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), British Columbia Cancer Agency, Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), School of Population Health, and University of Auckland [Auckland]

Subjects
Adult, Male, medicine.medical_specialty, Matching (statistics), Canada, Time Factors, Operations research, Epidemiology, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Matched-Pair Analysis, Decile, Interviews as Topic, 03 medical and health sciences, 0302 clinical medicine, Bias, Risk Factors, medicine, Odds Ratio, Humans, 030212 general & internal medicine, Israel, media_common, Selection bias, business.industry, Case-control study, Australia, Environmental exposure, Odds ratio, Environmental Exposure, Glioma, Middle Aged, Cellular telephone, 030220 oncology & carcinogenesis, Case-Control Studies, Epidemiologic Research Design, Female, France, MESH: Cellular telephone, Glioma, Matching, Case-control study, business, Cell Phone, Demography, New Zealand
Abstract

Purpose Associations between cellular telephone use and glioma risk have been examined in several epidemiological studies including the 13-country INTERPHONE study. Although results showed no positive association between cellular telephone use and glioma risk overall, no increased risk for long-term users, and no exposure-response relationship, there was an elevated risk for those in the highest decile of cumulative call time. However, results may be biased as data were collected during a period of rapidly increasing cellular telephone use, and as controls were usually interviewed later in time than cases. Methods Further analyses were conducted in a subset of five INTERPHONE study countries (Australia, Canada, France, Israel, New Zealand) using a post hoc matching strategy to optimize proximity of case-to-control interview dates and age. Results Although results were generally similar to the original INTERPHONE study, there was some attenuation of the reduced odds ratios and stronger positive associations among long-term users and those in the highest categories for cumulative call time and number of calls (eighth–ninth and 10th decile). Conclusions Proximity and symmetry in timing of case-to-control interviews should be optimized when exposure patterns are changing rapidly with time.

Published
2016
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22. Combined genetic and splicing analysis of BRCA1 c.[594-2A > C; 641A > G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms

Author

Barbara Wappenschmidt, Fergus J. Couch, Norbert Arnold, Claude Houdayer, Manjeet K. Bolla, Omar Soukarieh, Sean V. Tavtigian, Irene L. Andrulis, Alexandra Becker, Alexandra Martins, Qin Wang, Sara Margolin, Paolo Radice, Janet E. Olson, Mitul Shah, Juul T. Wijnen, Amanda B. Spurdle, Nichola Johnson, Carole Brewer, Harald Surowy, Graham G. Giles, Ana Blanco, Kamila Czene, Thomas Hansen, Wendy S. Rubinstein, Anja Rudolph, Christian F. Singer, Antonis C. Antoniou, Douglas F. Easton, Fiona M. Blows, Michael T. Parsons, kConFab Investigators, Annika Lindblom, Nicola K. Poplawski, Melissa C. Southey, Emily Hallberg, Vanessa Lattimore, Yvette van Ierland, Logan C. Walker, Joe Dennis, Gord Glendon, Ana Vega, Diether Niederacher, Laurent Castera, David E. Goldgar, Ulrike Faust, Roger L. Milne, Marta Santamariña, Lesley McGuffog, Jan Hauke, Christi J. van Asperen, Michela Raponi, Irene López-Perolio, Diana Baralle, Tina Pesaran, Huong Meeks, Peter J. Hulick, Miguel de la Hoya, Philip Whiley, Raquel Behar, Jenny Chang-Claude, Elizabeth C. Chao, Henrik Flyger, Doris Steinemann, Pham Phuong Mai, Stig E. Bojesen, Maaike P.G. Vreeswijk, Sandrine M. Caputo, Jan Sullivan, Julian Peto, Barbara Burwinkel, Laura Galastri, Per Hall, Kyriaki Michailidou, Bernd Dworniczak, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Fundación Pública Galega Medicina Xenómica-SERGAS & Grupo de Medicina Xenómica--USC, CIBER de Enfermedades Raras (CIBERER), Division of Genetics and Population Health, Queensland Institute of Medical Research, Genetics, University of Southampton, University of Otago [Dunedin, Nouvelle-Zélande], Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, Human Genetics Division [Southampton], Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Institut Laue-Langevin (ILL), University of Melbourne, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, Institute of Cell and Molecular Pathology, Medizinische Hochschule Hannover (MHH), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), DIEP/DSV (DIEP/DSV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Ambry Genetics [Aliso Viejo, CA, USA], Department of Clinical Genetics, Royal Devon & Exeter Hospital, Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Metabolic Unit, Dept Clinical Chemistry, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), Molecular Epidemiology Research Group, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Breast Surgery, Herlev and Gentofte Hospital, Karolinska University Hospital [Stockholm], Division of Cancer Epidemiology, Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medici, Cancer Epidemiology Centre, Cancer Council Victoria, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Science and Technology Beijing [Beijing] (USTB), Strangeways Research Laboratory, University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Cancer Research U.K. Genetic Epidemiology Unit, Department of Laboratory Medicine and Pathology, Mayo Clinic, Department of Oncological Sciences, University of Utah-Huntsman Cancer Institute, Center for Human and Clinical Genetics, Université de Pau et des Pays de l'Adour (UPPA), International Agency for Cancer Research (IACR), ILL, Service de Biochimie et de Biologie Moléculaire [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Antoniou, Antonis [0000-0001-9223-3116], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, Adult, RNA Splicing, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Breast Neoplasms, Biology, 03 medical and health sciences, Exon, Genetics, Humans, Allele, Molecular Biology, Gene, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Aged, Ovarian Neoplasms, Messenger RNA, BRCA1 Protein, Tumor Suppressor Proteins, Alternative splicing, RNA, General Medicine, Articles, Exons, Middle Aged, Splicing regulatory element, 3. Good health, Gene Expression Regulation, Neoplastic, Alternative Splicing, 030104 developmental biology, RNA splicing, Mutation, Female, RNA Splice Sites
Abstract

A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A>C (IVS9-2A>C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic BRCA1 variant. We used large-scale genetic and clinical resources from the ENIGMA, CIMBA and BCAC consortia to assess pathogenicity of c.594-2A>C. The combined odds for causality considering case-control, segregation, and breast tumor pathology information was 3.23x10-8. Our data indicate that c.594-2A>C is always in cis with c.641A>G.The spliceogenic effect of c.[594-2A>C;641A>G] was characterized using RNA analysis of human samples and splicing minigenes. As expected, c.[594-2A>C; 641A>G] caused exon 10 skipping, albeit not due to c.594-2A>C impairing the acceptor site but rather by c.641A>G modifying exon 10 splicing regulatory element(s). Multiple blood-based RNA assays indicated that the variant allele did not produce detectable levels of full-length transcripts, with a per allele BRCA1 expression profile comprised of ?70-80% truncating transcripts, and ?20-30% of in-frame ?9,10 transcripts predicted to encode a BRCA1 protein with tumor suppression function.We confirm that BRCA1c.[594-2A>C;641A>G] should not be considered a high-risk pathogenic variant. Importantly, results from our detailed mRNA analysis suggest that BRCA-associated cancer risk is likely not markedly increased for individuals who carry a truncating variant in BRCA1 exons 9 or 10, or any other BRCA1 allele that permits 20-30% of tumor suppressor function. More generally, our findings highlight the importance of assessing naturally occurring alternative splicing for clinical evaluation of variants in disease-causing genes.

Published
2016
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23. A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk

Author

Travis, Ruth, Appleby, Paul, Martin, Richard, Holly, Jeff M.P., Albanes, Demetrius, Black, Amanda, Bueno-De-Mesquita, H. Bas, Chan, June, Chen, Chu, Chirlaque, María-Dolores, Cook, Michael, Deschasaux, Mélanie, Donovan, Jenny, Ferrucci, Luigi, Galan, Pilar, Giles, Graham, Giovannucci, Edward, Gunter, Marc, Habel, Laurel, Hamdy, Freddie, Helzlsouer, Kathy, Hercberg, Serge, Hoover, Robert, Janssen, Joseph A.M.J.L., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loïc, Metter, E. Jeffrey, Mikami, Kazuya, Morris, Joan, Neal, David, Neuhouser, Marian, Ozasa, Kotaro, Palli, Domenico, Platz, Elizabeth, Pollak, Michael, Price, Alison, Roobol, Monique, Schaefer, Catherine, Schenk, Jeannette, Severi, Gianluca, Stampfer, Meir, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine, Touvier, Mathilde, Wald, Nicholas, Weiss, Noel, Ziegler, Regina, Key, Timothy, Allen, Naomi, Nuffield Department of Population Health [Oxford], University of Oxford [Oxford], School of Social and Community Medicine [Bristol], University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of California [San Francisco] (UCSF), University of California, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute on Aging [Bethesda, USA] (NIA), University of Melbourne, Harvard School of Public Health, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Kaiser Permanente, Nuffield (Nuffield), Mercy Medical Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Occupational and Environmental Health [Kitakyushu] (UEOH), University of Hawai‘i [Mānoa] (UHM), Kyoto Prefectural University of Medicine [Kyoto, Japon], Queen Mary University of London (QMUL), University of Cambridge [UK] (CAM), Radiation Effects Research Foundation, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Cancer Prevention Research Unit, Department of Oncology, McGill University = Université McGill [Montréal, Canada]-Jewish General Hospital, University of Washington [Seattle], Cancer Epidemiology Centre, Cancer Council Victoria, Human Genetics Foundation (HuGeF), Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Hokkaido University Hospital [Sapporo], University of Oxford, University of California [San Francisco] (UC San Francisco), University of California (UC), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Deschasaux-Tanguy, Mélanie

Subjects
Urologic Diseases, Male, Aging, Oncology and Carcinogenesis, Article, growth-factor-i, serum-insulin, Risk Factors, prevention trial, Humans, Oncology & Carcinogenesis, Insulin-Like Growth Factor I, factor axis, igfbp-3, Cancer, Aged, Prostate Cancer, hyperplasia, Prostatic Neoplasms, Middle Aged, susceptibility loci, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, factor-binding protein-2, Centre for Surgical Research, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, factor (igf)-i, diet, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. Aftermutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development.

Published
2016
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24. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

Author

Lawrenson, Kate, Kar, Siddhartha, McCue, Karen, Kuchenbaeker, Karoline, Michailidou, Kyriaki, Tyrer, Jonathan, Beesley, Jonathan, Ramus, Susan J., Li, Qiyuan, Delgado, Melissa K., Lee, Janet M., Aittomäki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arun, Banu K., Arver, Brita, Bandera, Elisa V., Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Benitez, Javier, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Anders, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Børresen-Dale, Anne Lise, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Bruinsma, Fiona, Brunet, Joan, Buhari, Shaik Ahmad, Burwinkel, Barbara, Butzow, Ralf, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Canniotto, Rikki, Chang-Claude, Jenny, Chiquette, Jocelyne, Choi, Ji Yeob, Claes, Kathleen B M, Cook, Linda S., Cox, Angela, Cramer, Daniel W., Cross, Simon S., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., Damiola, Francesca, Dansonka-Mieszkowska, Agnieszka, Darabi, Hatef, Dennis, Joe, Devilee, Peter, Diez, Orland, Doherty, Jennifer A., Domchek, Susan M., Dorfling, Cecilia M., Dörk, Thilo, Dumont, Martine, Ehrencrona, Hans, Ejlertsen, Bent, Ellis, Steve, Engel, Christoph, Lee, Eunjung, Evans, D. Gareth, Fasching, Peter A., Feliubadalo, Lidia, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Foretova, Lenka, Fostira, Florentia, Foulkes, William D., Fridley, Brooke L., Friedman, Eitan, Frost, Debra, Gambino, Gaetana, Ganz, Patricia A., Garber, Judy, García-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Ghoussaini, Maya, Giles, Graham G., Glasspool, Rosalind, Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Goode, Ellen L., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hallberg, Emily, Hamann, Ute, Hansen, Thomas V O, Harrington, Patricia A., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Heitz, Florian, Herzog, Josef, Høgdall, Estrid, Høgdall, Claus K., Hogervorst, Frans B L, Hollestelle, Antoinette, Hopper, John L., Hulick, Peter J., Huzarski, Tomasz, Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jensen, Allan, John, Esther M., Johnson, Nichola, Kabisch, Maria, Kang, Daehee, Kapuscinski, Miroslav, Karlan, Beth Y., Khan, Sofia, Kiemeney, Lambertus A., Kjaer, Susanne Kruger, Knight, Julia A., Konstantopoulou, Irene, Kosma, Veli Matti, Kristensen, Vessela, Kupryjanczyk, Jolanta, Kwong, Ava, De La Hoya, Miguel, Laitman, Yael, Lambrechts, Diether, Le, Nhu, De Leeneer, Kim, Lester, Jenny, Levine, Douglas A., Li, Jingmei, Lindblom, Annika, Long, Jirong, Lophatananon, Artitaya, Loud, Jennifer T., Lu, Karen, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Le Marchand, Loic, Margolin, Sara, Marme, Frederik, Massuger, Leon F A G, Matsuo, Keitaro, Mazoyer, Sylvie, McGuffog, Lesley, McLean, Catriona, McNeish, Iain, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R., Milne, Roger L., Montagna, Marco, Moysich, Kirsten B., Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Ness, Roberta B., Neuhausen, Susan L., Nevanlinna, Heli, Nord, Silje, Nussbaum, Robert L., Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olson, Janet E., Olswold, Curtis, O'Malley, David, Orlow, Irene, Orr, Nick, Osorio, Ana, Park, Sue Kyung, Pearce, Celeste L., Pejovic, Tanja, Peterlongo, Paolo, Pfeiler, Georg, Phelan, Catherine M., Poole, Elizabeth M., Pylkäs, Katri, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad Usman, Rennert, Gad, Rhenius, Valerie, Rhiem, Kerstin, Risch, Harvey A., Rodriguez, Gus, Rossing, Mary Anne, Rudolph, Anja, Salvesen, Helga B., Sangrajrang, Suleeporn, Sawyer, Elinor J., Schildkraut, Joellen M., Schmidt, Marjanka K., Schmutzler, Rita K., Sellers, Thomas A., Seynaeve, Caroline, Shah, Mitul, Shen, Chen Yang, Shu, Xiao Ou, Sieh, Weiva, Singer, Christian F., Sinilnikova, Olga M., Slager, Susan, Song, Honglin, Soucy, Penny, Southey, Melissa C., Stenmark-Askmalm, Marie, Stoppa-Lyonnet, Dominique, Sutter, Christian, Swerdlow, Anthony, Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Tibiletti, Maria Grazia, Tihomirova, Laima, Tognazzo, Silvia, Toland, Amanda Ewart, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Tseng, Chiu Chen, Tung, Nadine, Tworoger, Shelley S., Vachon, Celine, Van Den Ouweland, Ans M W, Van Doorn, Helena C., Van Rensburg, Elizabeth J., Van't Veer, Laura J., Vanderstichele, Adriaan, Vergote, Ignace, Vijai, Joseph, Wang, Qin, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Wentzensen, Nicolas, Whittemore, Alice S., Wildiers, Hans, Winqvist, Robert, Wu, Anna H., Yannoukakos, Drakoulis, Yoon, Sook Yee, Yu, Jyh Cherng, Zheng, Wei, Zheng, Ying, Khanna, Kum Kum, Simard, Jacques, Monteiro, Alvaro N., French, Juliet D., Couch, Fergus J., Freedman, Matthew L., Easton, Douglas F., Dunning, Alison M., Pharoah, Paul D., Edwards, Stacey L., Chenevix-Trench, Georgia, Antoniou, Antonis C., Gayther, Simon A., Bowtell, David, DeFazio, Anna, Webb, Penny, Collonge-Rame, Marie Agnès, Damette, Alexandre, Barouk-Simonet, Emmanuelle, Bonnet, Françoise, Bubien, Virginie, Sevenet, Nicolas, Longy, Michel, Berthet, Pascaline, Vaur, Dominique, Castera, Laurent, Ferrer, Sandra Fert, Bignon, Yves Jean, Uhrhammer, Nancy, Coron, Fanny, Faivre, Laurence, Baurand, Amandine, Jacquot, Caroline, Bertolone, Geoffrey, Lizard, Sarab, Leroux, Dominique, Dreyfus, Hélène, Rebischung, Christine, Peysselon, Magalie, Peyrat, Jean Philippe, Fournier, Joëlle, Révillion, Françoise, Adenis, Claude, Vénat-Bouvet, Laurence, Léone, Mélanie, Boutry-Kryza, Nadia, Calender, Alain, Giraud, Sophie, Verny-Pierre, Carole, Lasset, Christine, Bonadona, Valérie, Barjhoux, Laure, Sobol, Hagay, Bourdon, Violaine, Noguchi, Tetsuro, Remenieras, Audrey, Coupier, Isabelle, Pujol, Pascal, Sokolowska, Johanna, Bronner, Myriam, Delnatte, Capucine, Bézieau, Stéphane, Mari, Véronique, Gauthier-Villars, Marion, Buecher, Bruno, Rouleau, Etienne, Golmard, Lisa, Moncoutier, Virginie, Belotti, Muriel, De Pauw, Antoine, Elan, Camille, Fourme, Emmanuelle, Birot, Anne Marie, Saule, Claire, Laurent, Maïté, Houdayer, Claude, Lesueur, Fabienne, Mebirouk, Noura, Coulet, Florence, Colas, Chrystelle, Soubrier, Florent, Warcoin, Mathilde, Prieur, Fabienne, Lebrun, Marine, Kientz, Caroline, Muller, Danièle, Fricker, Jean Pierre, Toulas, Christine, Guimbaud, Rosine, Gladieff, Laurence, Feillel, Viviane, Mortemousque, Isabelle, Bressac-De-Paillerets, Brigitte, Caron, Olivier, Guillaud-Bataille, Marine, Gregory, Helen, Miedzybrodzka, Zosia, Morrison, Patrick J., Donaldson, Alan, Rogers, Mark T., Kennedy, M. John, Porteous, Mary E., Brady, Angela, Barwell, Julian, Foo, Claire, Lalloo, Fiona, Side, Lucy E., Eason, Jacqueline, Henderson, Alex, Walker, Lisa, Cook, Jackie, Snape, Katie, Murray, Alex, McCann, Emma, Rookus, M. A., Van Leeuwen, F. E., Van Der Kolk, L. E., Schmidt, M. K., Russell, N. S., De Lange, J. L., Wijnands, R., Collée, J. M., Hooning, M. J., Seynaeve, C., Van Deurzen, C. H M, Obdeijn, I. M., Van Asperen, C. J., Tollenaar, R. A E M, Van Cronenburg, T. C T E F, Kets, C. M., Ausems, M. G E M, Van Der Pol, C. C., Van Os, T. A M, Waisfisz, Q., Meijers-Heijboer, H. E J, Gómez-Garcia, E. B., Oosterwijk, J. C., Mourits, M. J., De Bock, G. H., Vasen, H. F., Siesling, S., Verloop, J., Overbeek, L. I H, Fox, Stephen, Kirk, Judy, Lindeman, Geoff, Price, Melanie, NIH - National Cancer Institute (NCI) (Estados Unidos), National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Dutch Cancer Society (Holanda), Breast Cancer Research Trust, Instituto de Salud Carlos III, Lon V. Smith Foundation, Federal Ministry of Education & Research (Alemania), Finlands Akademi (Finlandia), United States Army Medical Research and Development Command, California Breast Cancer Research Program, German Cancer Aid, Canadian Institutes of Health Research, Ministère de Économie, Innovation et Exportation (Canadá), Ministry of Higher Education (Malasia), National Medical Research Council (Singapur), University of Oulu (Finlandia), Yorkshire Cancer Research, Hellenic Cooperative Oncology Group, California Cancer Research Program, Danish Cancer Society, Ministry of Science and Higher Education (Polonia), Asociación Española Contra el Cáncer, University of Kansas. Cancer Center (Estados Unidos), Hungarian Research Grants, Norwegian EEA Financial Mechanism, Canadian Breast Cancer Network, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Congressionally Directed Medical Research Programs (Estados Unidos), NRG Oncology National (Estados Unidos), Unión Europea. Comisión Europea. 7 Programa Marco, Medical Oncology, Obstetrics & Gynecology, Clinical Genetics, 1 Department of Preventive Medicine, Keck School of MediCenter, Kansas City, Kansas 66160, USA. 90 Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer 52621, Israel. 91 Section of Genetic Oncology, Department of Laboratory Medicine, University and University Hospital of Pisa, Pisa 56126, Italy. 92 UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center, Los Angeles, California 90024, USA. 93 Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 94 Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK. 95Women’s Cancer, UCL EGA Institute for Women’s Health, London WC1E 6AU, UK. 96 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia. 97 Cancer Research UK Clinical Trials Unit, The BeatsonWest of Scotland Cancer Centre, Glasgow G12 0YN, UK. 98 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. 99 Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montreal, Que´bec H3A 1A1, Canada. 100 Department of Medicine, McGill University, Montreal, Que´bec H3A 1A1, Canada. 101 Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. 102 Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55902, USA. 103 Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 104Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 105 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892, USA. 106 Department of Genetics and Pathology, Pomeranian Medical University, 70-204 Szczecin, Poland. 107 Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, 94805 Villejuif, France. 108 University Paris- Sud, 91405 Villejuif, France. 109 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 110 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark. 111 Department of Oncology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK. 112 Saw Swee Hock School of Public Health, National University of Singapore Singapore 119077, Singapore. 113 Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, 50603 Kuala Lumpur, Malaysia. 114 Cancer Research Initiatives Foundation, Subang Jaya, 47500 Selangor, Malaysia. 115 Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136 Essen, Germany. 116 Department of Gynecology and Gynecologic Oncology, Dr Horst Schmidt Kliniken Wiesbaden, 65199 Wiesbaden, Germany. 117 Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte California 91010, USA. 118 Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, 2730 Copenhagen, Denmark. 119 Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark. 120 Department of Gynecology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark. 121 Family Cancer Clinic, Netherlands Cancer Institute, 1006 Amsterdam, The Netherlands. 122 Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, 3015 Rotterdam, The Netherlands. 123 Center for Medical Genetics, NorthShore University Health System, Evanston, Illinois 60201, USA. 124 N.N. Petrov Institute of Oncology, St Petersburg 197758, Russia. 125 Lombardi Comprehensive Cancer Center, Georgetown University, Washington District of Columbia 20057, USA. 126 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi 464-8681, Japan. 127 State Research Institute Centre for Innovative Medicine, LT-01102 Vilnius, Lithuania. 128 Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California 94538, USA. 129 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 08826, Korea. 130 Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria 3010, Australia. 131Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 132 Radboud University Medical Centre, Radboud Institute for Health Sciences, 6500 Nijmegen, The Netherlands. 133 Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. 134 Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5T 3M7, Canada. 135 Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, 70210 Kuopio, Finland. 136 Cancer Center, Kuopio University Hospital, 70210 Kuopio, Finland. 137 Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, 70210 Kuopio, Finland. 138 Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, 1478 Oslo, Norway. 139 The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China. 140 Department of Surgery, The University of Hong Kong, Hong Kong, China. 141Vesalius Research Center, VIB, 3000 Leuven, Belgium. 142 Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000 Leuven, Belgium. 143 Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden. 144 Division of Health Sciences, Warwick Medical School, Warwick University, Coventry CV4 7AL, UK. 145 Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 146 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), 20133 Milan, Italy. 147 University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA. 148 Department of Oncology - Pathology, Karolinska Institutet, SE- 171 77 Stockholm, Sweden. 149 National Center for Tumour Diseases, University of Heidelberg, 69117 Heidelberg, Germany. 150 Department of Gynaecology, Radboud University Medical Centre, 6500 Nijmegen, The Netherlands. 151 Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka 812-8582, Japan. 152 Anatomical Pathology, The Alfred Hospital, Melbourne, Victoria 3004, Australia. 153 Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow G61 1BD, UK. 154 Division of Gynaecology and Obstetrics, Technische Universita¨t Mu¨nchen, 81675 Munich, Germany. 155 Department of Human Genetics, Radboud University Medical Centre, 6500 Nijmegen, The Netherlands. 156 Immunology and Molecular Oncology Unit, Instituto Oncologico Veneto IOV, IRCCS, 35128 Padua, Italy. 157 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 158 Institute of Population Health, University of Manchester, Manchester M13 9PL, UK. 159 Laboratory Medicine Program, University Health Network, Toronto, Ontario M5G 1L7, Canada. 160 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L7, Canada. 161 The University of Texas School of Public Health, Houston, Texas 77030, USA. 162 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA. 163 Department of Medicine and Genetics, University of California, San Francisco, California 94143, USA. 164 Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 165 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. 166 Department of Molecular Genetics, National Institute of Oncology, 1122 Budapest, Hungary. 167 Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois 60637, USA. 168 The Ohio State University and the James Cancer Center, Columbus, Ohio 43210, USA. 169 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York 10017, USA. 170 Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), 28019 Madrid, Spain. 171 Biomedical Network on Rare Diseases (CIBERER), 28029 Madrid, Spain. 172 Department of Surgery, Seoul National University College of Medicine, Seoul, 03080 Korea. 173 Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon 97239, USA. 174 Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA. 175 IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, 16 20139 Milan, Italy. 176 Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria. 177 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida 33606, USA. 178 Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 179 Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts 02115, USA. 180 Laboratory of Cancer Genetics and Tumour Biology, Northern Finland Laboratory Centre NordLab, FI-90014 Oulu, Finland. 181 Laboratory of Cancer Genetics and Tumour Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland. 182 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT),cine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA. 2 Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK. 3 QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia. 4 Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK. 5 Medical College, Xiamen University, Xiamen 361102, China. 6 Department of Medical Oncology, The Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 7 Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki 00029 HUS, Finland. 8 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario Canada, M5G 1X5. 9 Department of Molecular Genetics, University of Toronto, Toronto, OntarioCanada, M5S 1A8. 10 Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, California 92697, USA. 11 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany. 12 University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 13 Department of Oncology, Karolinska University Hospital, Stockholm 171 77, Sweden. 14 Cancer Prevention and Control, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA. 15 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan 20141, Italy. 16 Department of Pathology, Landspitali University Hospital and BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik 600169- 2039, Iceland. 17 University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen 91054, Germany. 18 Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid E-28029, Spain. 19 Centro de Investigacio´n en Red de Enfermedades Raras, Valencia 28029, Spain. 20 Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27710, USA. 21 Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. 22 Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway. 23 Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway. 24 Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki FIN-00029, Finland. 25 Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA. 26 International Epidemiology Institute, Rockville, Maryland 20850, USA. 27 Gynaecology Research Unit, Hannover Medical School, Hannover D-30625, Germany. 28 Department of Clinical Genetics, Vejle Hospital, Vejle 7100, Denmark. 29 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. 30 Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 31 Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 32 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo N-0310, Norway. 33 K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo N-0310, Norway. 34 Dr Margarete Fischer- Bosch-Institute of Clinical Pharmacology, Stuttgart D-70376, Germany. 35 University of Tu¨bingen, Tu¨bingen 72074, Germany. 36 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 37 International Agency for Research on Cancer, Lyon 69008, France. 38 Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 39 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia. 40 Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d’Investigacio´ Biome`dica de Girona), Catalan Institute of Oncology, Girona 08908, Spain. 41 Department of Surgery, National University Health System, Singapore 119077, Singapore. 42 Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 43 Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg 69120, Germany. 44 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki 00029 HUS, Finland. 45 Department of Pathology, Helsinki University Central Hospital, Helsinki 00029, Finland. 46 Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA. 47 Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigacio´n Sanitaria del Hospital Clı ´nico San Carlos), Madrid 28040, Spain. 48 Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia. 49 Cancer Pathology & Prevention, Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo 14263, New York, USA. 50 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 51 University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany. 52 Unite´ de recherche en sante´ des populations, Centre des maladies du sein Descheˆnes-Fabia, Centre de recherche FRSQ du Centre hospitalier affilie´ universitaire de Que´bec, Que´bec City, Que´bec Canada, G1J 1Z4. 53 Cancer Research Institute, Seoul National University, Seoul 08826, Korea. 54 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. 55 Center for Medical Genetics, Ghent University, Ghent 9000, Belgium. 56 Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87131, USA. 57 Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield S10 2TN, UK. 58 Harvard HT Chan School of Public Health, Boston, Massachusetts 02115, USA. 59 Obstetrics and Gynecology Epidemiology Center, Brigham andWomen’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 60 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2TN, UK. 61 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 70-115, Poland. 62 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm SE-171 77, Sweden. 63 Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. 64 INSERM U1052, CNRS UMR5286, Universite´ Lyon, Centre de Recherche en Cance´rologie de Lyon, Lyon 69373, France. 65 Department of Pathology and Laboratory Diagnostics the Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology,Warsaw 44-101, Poland. 66 Department of Pathology, Leiden University Medical Center, Leiden 2333, The Netherlands. 67 Department of Human Genetics, Leiden University Medical Center, Leiden 2333, The Netherlands. 68 Oncogenetics Group, University Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO) and Universitat Auto`noma de Barcelona, Barcelona, 186 Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, 50931 Cologne, Germany. 187Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut 06510, USA. 188Division of Gynecologic Oncology, NorthShore University HealthSystem, Evanston, Illinois 60201, USA. 189 Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. 190Department of Epidemiology, University of Washington, Seattle, Washington 98109, USA. 191National Cancer Institute, Bangkok 10400, Thailand. 192 Research Oncology, Guy’s Hospital, King’s College London, London SE1 9RT, UK. 193Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. 194 Cancer Control and Population Sciences, Duke Cancer Institute, Durham, North Carolina 27710, USA. 195Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands. 196Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, 50676 Cologne, Germany. 197 Center for Integrated Oncology, University Hospital of Cologne, 50676 Cologne, Germany. 198 Center for Molecular Medicine, University Hospital of Cologne, 50676 Cologne, Germany. 199 Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, 50676 Cologne, Germany. 200 Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. 201 School of Public Health, China Medical University, Taichung 404, Taiwan. 202Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford California 94305, USA. 203 Unite´ Mixte de Ge´ne´tique Constitutionnelle des Cancers Fre´quents, Hospices Civils de Lyon – Centre Le´on Be´rard, Lyon 69008, France. 204 INSERM U1052, CNRS UMR5286, Universite´ Lyon 1, Centre de Recherche en Cance´rologie de Lyon, Lyon 69003, France. 205Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia. 206Division of Clinical Genetics, Department of Clinical and Experimental Medicine, Linko¨ping University, 581 83 Linko¨ping, Sweden. 207 Institut Curie, Department of Tumour Biology, Paris, France, Institut Curie, INSERM U830, 75248 Paris, France. 208Universite´ Paris Descartes, Sorbonne Paris Cite´, 75270 Paris, France. 209 Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany. 210Department of Genetics, Portuguese Oncology Institute, Porto 4200-072, Portugal. 211 Biomedical Sciences Institute (ICBAS), Porto University, Porto 4099-002, Portugal. 212Department of Epidemiology, Mailman School of Public Health, Columbia University, New York 10027, USA. 213Department of Clinical Genetics, Odense University Hospital, 5000 Odense C, Denmark. 214UO Anatomia Patologica, Ospedale di Circolo-Universita` dell’Insubria, 21100 Varese, Italy. 215 Latvian Biomedical Research and Study Centre, Riga LV-1067, Latvia. 216 Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), 64 - 35128 Padua, Italy. 217Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA. 218Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7BN, UK. 219 Institute of Human Genetics, Pontificia Universidad Javeriana, Cra. 7 #40-62 Bogota, Colombia. 220Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. 221Department of Clinical Genetics, Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands. 222Department of Gynecology, Family Cancer Clinic, Erasmus MC Cancer Institute, 3015 CE Rotterdam, The Netherlands. 223Division of Gynecological Oncology, Department of Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. 224University Hospital Ulm, 89069 Ulm, Germany. 225Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda Maryland 20892, USA. 226 Multidisciplinary Breast Center, Department of General Medical Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. 227 Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research ‘Demokritos’, Athens 153 10, Greece. 228 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, 47500 Subang Jaya, Malaysia. 229 University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Malaysia. 230Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114 Taiwan. 231 Shanghai Center for Disease Control and Prevention, Shanghai, China. 232 Cancer Epidemiology Program, Division of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. 233Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. 234 Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. 235 Sir Peter MacCallum Cancer Centre Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia. 236 Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK. 237 Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3052, Australia. 238 Department of Gynaecological Oncology, Westmead Institute for Cancer Research, Westmead Hospital Westmead, New South Wales 2145, Australia., Tyrer, Jonathan [0000-0003-3724-4757], Dennis, Joe [0000-0003-4591-1214], Rhenius, Valerie [0000-0003-4215-3235], Song, Honglin [0000-0001-5076-7371], Wang, Jean [0000-0002-9139-0627], Easton, Douglas [0000-0003-2444-3247], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Epidemiology and Data Science, EMGO - Quality of care, Anesthesiology, Human genetics, CCA - Cancer biology, and VU University medical center

Subjects
endocrine system diseases, Messenger, IDENTIFIES 3, MODIFIERS, Brjóstakrabbamein, BRCA2 MUTATION CARRIERS, Medicine and Health Sciences, GWAS, INVESTIGATORS, African Continental Ancestry Group, Asian Continental Ancestry Group, Breast Neoplasms, Chromosomes, Human, Pair 19, Female, Genome-Wide Association Study, Genotype, Humans, Ovarian Neoplasms, RNA, Messenger, Alleles, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, skin and connective tissue diseases, COMMON VARIANTS, EPITHELIAL-CELLS, Single Nucleotide, female genital diseases and pregnancy complications, NAF12, Medical Genetics, Human, endocrine system, Science, Chromosomes, Human, Pair 19/genetics, Black People, Breast Neoplasms/genetics, Chromosomes, Article, Ovarian Neoplasms/genetics, SDG 3 - Good Health and Well-being, Asian People, REVEALS, Polymorphism, GENOME-WIDE ASSOCIATION, Krabbamein, Medicinsk genetik, Cancer och onkologi, Pair 19, Arfgengi, GENE, Eggjastokkar, Cancer and Oncology, RNA, BRCA1 Protein/genetics
Abstract

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P, A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Published
2016
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25. Tools for translational epigenetic studies involving formalin-fixed paraffin-embedded human tissue: applying the Infinium HumanMethyation450 Beadchip assay to large population-based studies

Author

Melissa C. Southey, Jihoon E. Joo, Dallas R. English, John L. Hopper, Graham G. Giles, Laura Baglietto, Liesel M. FitzGerald, Catriona McLean, Gianluca Severi, Roger L. Milne, Ee Ming Wong, Bodescot, Myriam, Department of Pathology, University of Melbourne, Department of Anatomical Pathology, The Alfred Hospital, Cancer Epidemiology Centre, Cancer Council Victoria, Centre for Epidemiology and Biostatistics, Cohort recruitment was funded by VicHealth and Cancer Council Victoria. This work was further supported by the National Health and Medical Research Council (NHMRC, and APP1011618 and APP1026892) and The Victorian Breast Cancer Research Consortium. MCS is a NHMRC SRF and VBCRC Group Leader. JLH is a NHMRC SPRF. LMF is the Cancer Council Victoria David Hill Fellow and is funded by a Movember and Cure Cancer Australia Foundation Young Investigator Grant awarded through Prostate Cancer Foundation of Australia’s Research Program.

Subjects
Genetics and Molecular Biology (all), Tissue Fixation, Breast tumour subtype, Bisulfite sequencing, Gene Expression, Triple Negative Breast Neoplasms, Bioinformatics, BRCA1, DNA methylation, Epigenetics, Formalin-fixed paraffin-embedded, HM450K beadchip, Population-based translational epigenetic studies, Adult, Aged, BRCA1 Protein, Cohort Studies, DNA Methylation, DNA, Neoplasm, Female, Fixatives, Formaldehyde, Humans, Middle Aged, Oligonucleotide Array Sequence Analysis, Paraffin Embedding, Epigenesis, Genetic, Genome, Human, Biochemistry, Genetics and Molecular Biology (all), Medicine (all), Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Technical Note, Medicine(all), 0303 health sciences, education.field_of_study, Genome, General Medicine, Methylation, 3. Good health, 030220 oncology & carcinogenesis, Human, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Genetic, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, 030304 developmental biology, Biochemistry, Genetics and Molecular Biology(all), DNA, medicine.disease, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Neoplasm, Human genome, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Epigenesis
Abstract

Background Large population-based translational epigenetic studies are emerging due to recent technological advances that have made molecular analyses possible. For example, the Infinium HumanMethylation450 Beadchip (HM450K) has enabled studies of genome-wide methylation on a scale not previously possible. However, application of the HM450K to DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour material has been more challenging than application to high quality DNA extracted from blood. To facilitate the application of this assay consistently across a large number of FFPE tumour-enriched DNA samples we have devised a modification to the HM450K protocol for FFPE that includes an additional quality control (QC) checkpoint. Results QC checkpoint 3 was designed to assess the presence of DNA after bisulfite conversion and restoration, just prior to application of the HM450K assay. DNA was extracted from 474 archival FFPE breast tumour material. Five samples did not have a detectable amount of DNA with an additional 42 failing to progress past QC checkpoint 3. Genome-wide methylation was measured for the remaining 428 tumour-enriched DNA. Of these, only 4 samples failed our stringent HM450K data criteria thus representing a 99 % success rate. Using prior knowledge about methylation marks associated with breast cancer we further explored the quality of the data. Twenty probes in the BRCA1 promoter region showed increased methylation in triple-negative breast cancers compared to Luminal A, Luminal B and HER2-positive breast cancer subtypes. Validation of this observation in published data from The Cancer Genome Atlas (TCGA) Network (obtained from DNA extracted from fresh frozen tumour samples) confirms the quality of the data obtained from the improved protocol. Conclusions The modified protocol is suitable for the analysis of FFPE tumour-enriched DNA and can be systematically applied to hundreds of samples. This protocol will have utility in population-based translational epigenetic studies and is applicable to a wide variety of translated studies interested in analysis of methylation and its role in the predisposition to disease and disease progression. Electronic supplementary material The online version of this article (doi:10.1186/s13104-015-1487-z) contains supplementary material, which is available to authorized users.

Published
2015
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26. Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study

Author

Sabina Rinaldi, Aurelio Barricarte, Dimitrios Trichopoulos, Evelyn M. Monninkhof, Françoise Clavel-Chapelon, Anne Tjønneland, Amalia Mattiello, Laure Dossus, Renée T. Fortner, Virginia Menéndez, Vittorio Krogh, Kim Overvad, Fulvio Ricceri, Antonia Trichopoulou, Rosario Tumino, Laura Baglietto, Kaja Tikk, Elisabete Weiderpass, Disorn Sookthai, Ruth C. Travis, Timothy J. Key, María José Sánchez, Antonio Agudo, Giovanna Masala, Isabelle Romieu, Elio Riboli, Heiner Boeing, María Dolores Chirlaque, Malin Sund, Theron Johnson, Anja Olsen, N. Charlotte Onland-Moret, Anne Andresson, Rudolf Kaaks, Hbas Bueno-de-Mesquita, Pagona Lagiou, Pilar Amiano, Kay-Tee Khaw, Melissa A. Merritt, [Tikk,K, Sookthai,D, Fortner,RT, Johnson,T, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Rinaldi,S, Romieu,I] Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France. [Tjønneland,D, Olsen,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Dossus,l] INSERM, Centre for Research in Epidemiology and Population Health [CESP], Nutrition, Hormones and Women’s Health team, Villejuif, France. [Clavel-Chapelon,F, Dossus,l] Univ Paris Sud, Villejuif, France. [Clavel-Chapelon,F, Dossus,l] IGR, Villejuif, France. [Baglietto,L] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Australia. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece.[Trichopoulou,A, Lagiou.P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P.Arezzo' Hospital ASP, Ricceri, Ragusa, Italy. [Ricceri,F] Unit of Cancer Epidemiology, AO Citta’ della Salute e della Scienza, University of Turin, Torino, Italy. Unit of Cancer Epidemiology, AO Citta’ della Salute e della Scienza, University of Turin, Torino, Italy. [Mattiello,A] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Agudo,A] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Menéndez,V] Public Health Directorate, Asturias, Spain. [Sánchez,M] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitario de Granada (Granada.ibs), Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Reserach Institute, San Sebastian, Spain. [Chirlaque,M] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Sánchez, M, Amiano, P, Chirlaque,M, Barricarte,A] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER de Epidemiología y Salud Pública (CIBERESP)), Madrid, Spain. [Bueno-de-Mesquita,H] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Bueno-de-Mesquita,H, Merritt,MA, Riboli,E] Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College, London, UK. [Monninkhof,EM, Onland-Moret,NC] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Andresson,A] Department of Radiation Sciences, University of Umeå, Umeå, Sweden. [Sund,M] Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland, [Khaw,K] School of Clinical Medicine, University of Cambridge, Cambridge, UK. [Key,TJ, and Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Tikk,K] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.

Subjects
Oncology, Cancer Research, Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Gonadotropins::Gonadotropins, Pituitary::Prolactin [Medical Subject Headings], PERIOD, Prolactina, Cohort Studies, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Risk Factors, REPRODUCIBILITY, HISTORY, Odds Ratio, 0303 health sciences, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Neoplasias de la Mama, Estudios de Casos y Controles, Middle Aged, Adult, Aged, Breast Neoplasms, Carcinoma in Situ, Case-Control Studies, Europe, Female, Follow-Up Studies, Humans, Logistic Models, Menopause, Prolactin, 3. Good health, European Prospective Investigation into Cancer and Nutrition, POSTMENOPAUSAL WOMEN, PREMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], Cohort, Life Sciences & Biomedicine, Cohort study, Research Article, medicine.medical_specialty, CARCINOMA, STEROID-HORMONES, Riesgo, Càncer de mama, 03 medical and health sciences, Internal medicine, parasitic diseases, medicine, Journal Article, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Cancer och onkologi, Science & Technology, business.industry, Carcinoma in situ, Case-control study, Odds ratio, medicine.disease, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in Situ [Medical Subject Headings], Cancer and Oncology, PLASMA PROLACTIN, business
Abstract

Introduction The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention. Methods We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects. Results We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), P-trend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (P-het = 0.98) or baseline HT use (P-het = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (P-trend = 0.06 vs P-trend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors = 4 years after blood donation (P-trend = 0.01 vs P-trend = 0.63; P-het = 0.04) and among nulliparous women compared to parous women (P-trend = 0.03 vs P-trend = 0.15; P-het = 0.07). Conclusions Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.

Published
2015
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27. Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies

Author

Ruth C. Travis, Demetrius Albanes, Pilar Galan, H. Bas Bueno-de-Mesquita, Judy Hoffman-Bolton, Aurelio Barricarte, Harri Rissanen, Satu Männistö, Markku Heliövaara, Rebecca Gilbert, Timothy J. Key, Jenny L Donovan, Gary E. Goodman, Naomi E. Allen, Mathilde Touvier, Robert N. Hoover, Cindy Ke Zhou, Richard M. Martin, Jeannette M. Schenk, Regina G. Ziegler, Graham G. Giles, Irena B. King, Haakon E. Meyer, June M. Chan, Michael B. Cook, Meir J. Stampfer, Camille Pouchieu, Phyllis J. Goodman, Loic Le Marchand, Gianluca Severi, Elizabeth A. Platz, Amanda Black, Stephanie J. Weinstein, Marc J. Gunter, Marian L. Neuhouser, Freddie C. Hamdy, Alison M. Mondul, Laurence N. Kolonel, Serge Hercberg, Antonia Trichopoulou, Mattias Johansson, Kay-Tee Khaw, Anne Tjønneland, Anthony J. Alberg, Paul Knekt, Kathy J. Helzlsouer, Heiner Boeing, David E. Neal, Brian E. Henderson, Kristin A. Moy, Chu Chen, Edward Giovannucci, Paul N. Appleby, Domenico Palli, Nuffield Department of Population Health - Cancer Epidemiology Unit, University of Oxford [Oxford], Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Department of Epidemiology, The Netherlands Cancer Institute, Medical University of South Carolina [Charleston] (MUSC), Navarra Public Health Institute, Consortium for Biomedical Research in Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), German Institute of Human Nutrition, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Centre, School of Public Health, Imperial College London, University of California [San Francisco] (UCSF), University of California, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), School of Social and Community Medicine, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer Epidemiology Centre, Cancer Council Victoria, Harvard School of Public Health, Brigham and Women's Hospital [Boston], University of Washington [Seattle], National Institute of Health and Welfare, Prevention and Research Center, Mercy Medical Center, University of Southern California (USC), Johns Hopkins Bloomberg School of Public Health, Partenaires INRAE, International Agency for Research on Cancer (IARC), Umeå University, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM)-Institute of Public Health, The University of New Mexico [Albuquerque], Cancer Center, Massachusetts General Hospital [Boston], Medical Research Council, National Institute for Health Research (NHS), University of Oslo (UiO), Norwegian institute for public health, Department of Oncology, University of Cambridge [UK] (CAM), Istituto per lo Studio e la Prevezione Oncologica, Cancer Prevention Program, Institute of Cancer Epidemiology, The Danish Cancer Society, Hellenic Health Foundation, Bureau of Epidemiologic Research, Academy of Athens, ProdInra, Migration, University of Oxford, University of California [San Francisco] (UC San Francisco), and University of California (UC)

Subjects
Male, Oncology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], alpha-Tocopherol, Medicine (miscellaneous), Cohort Studies, chemistry.chemical_compound, Prostate cancer, Lycopene, Risk Factors, Prostate, Prospective Studies, Carotenoid, Cancer, chemistry.chemical_classification, Nutrition and Dietetics, Retinol, carotenoids, food and beverages, vitamin e, Middle Aged, prostate cancer, vitamin a, 3. Good health, [SDV] Life Sciences [q-bio], Observational Studies as Topic, medicine.anatomical_structure, pooled analysis, tocopherols, retinol, Adult, medicine.medical_specialty, Meta-Analysis as Topic, beta-Carotene, Internal medicine, medicine, Humans, Neoplasm Staging, nested case control study, business.industry, Vitamin E, Case-control study, Prostatic Neoplasms, biomarkers, medicine.disease, Cross-Sectional Studies, Endocrinology, chemistry, Case-Control Studies, Nested case-control study, Neoplasm Grading, business
Abstract

International audience; Background: Individual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease. Objective: The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, alpha-tocopherol, and gamma-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors. Design: Principal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets. Results: Data were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For alpha-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). gamma-Tocopherol was not associated with risk. Conclusions: Overall prostate cancer risk was positively associated with retinol and inversely associated with alpha-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and alpha-tocopherol. Whether these associations reflect causal relations is unclear.

Published
2015
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28. Association between melanocytic nevi and risk of breast diseases: The French E3N prospective cohort

Author

Sylvie Mesrine, Françoise Clavel-Chapelon, Alice Vilier, Laure Dossus, Laura Baglietto, Anne Bijon, Marie-Christine Boutron-Ruault, Marina Kvaskoff, Agnès Fournier, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], Cancer Control Group, QIMR Berghofer Medical Research Institute, Cancer Epidemiology Centre, The Cancer Council Victoria, Centre for Molecular , Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne-Centre for Molecular, Melbourne School of Population Health, This work was supported by the Mutuelle Generale de l’Education Nationale (MGEN), the European Community, the French League against Cancer (LNCC), Gustave Roussy, and the French National Institutes for Health and Medical Research (Inserm)). MK is financially supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078) (URL: http://ec.europa.eu/research/mariecurieactions/about-mca/actions/iof, Dupuis, Christine, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
Oncology, Adult, medicine.medical_specialty, Skin Neoplasms, [SDV]Life Sciences [q-bio], Breast Neoplasms, Family, Female, France, Humans, Logistic Models, Melanocytes, Middle Aged, Nevus, Premenopause, Proportional Hazards Models, Prospective Studies, Risk Factors, Medicine (all), lcsh:Medicine, Breast cancer, Internal medicine, Medicine and Health Sciences, medicine, Family history, skin and connective tissue diseases, 10. No inequality, Prospective cohort study, Gynecology, business.industry, lcsh:R, Absolute risk reduction, Cancer, General Medicine, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Perspective, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Breast disease, Skin cancer, business
Abstract

Background: While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk. Methods and Findings: We prospectively analyzed data from E3N, a cohort of French women aged 40–65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990–15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with ‘‘very many’’ nevi had a significantly higher breast cancer risk (HR=1.13, 95% CI=1.01–1.27 versus ‘‘none’’; ptrend=0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI=3,674–4,649) per 100,000 women with ‘‘very many’’ nevi. The association was restricted to premenopausal women (HR=1.40, ptrend=0.01), even after full adjustment (HR=1.34, ptrend=0.03; phomogeneity=0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose–response relationships between number of nevi and history of biopsy-confirmed BBD (n=5,169; ptrend,0.0001) and family history of breast cancer in first-degree relatives (n=7,472; ptrend=0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD. Conclusions: Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms. Please see later in the article for the Editors’ Summary.

Published
2014
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29. Allergy and brain tumors in the INTERPHONE study: pooled results from Australia, Canada, France, Israel, and New Zealand

Author

Michelle C. Turner, Marie-Élise Parent, Daniel Krewski, Graham G. Giles, Alistair Woodward, Bruce K. Armstrong, Martine Hours, Siegal Sadetzki, Elisabeth Cardis, Angela Chetrit, Jack Siemiatycki, Mary L. McBride, McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa [Ottawa], Sydney School of Public Health, The University of Sydney, Cancer and Radiation Epidemiology Unit, The Gertner Institute for Epidemiology and Health Policy Research, Cancer Epidemiology Centre, Cancer Council Victoria, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Cancer Control Research, British Columbia Cancer Agency, Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], School of Population Health, University of Auckland [Auckland], and Centre for Research in Environmental Epidemiology

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Acoustic neuroma, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Glioma, Epidemiology, otorhinolaryngologic diseases, medicine, Confidence Intervals, Hypersensitivity, Odds Ratio, Humans, Multicenter Studies as Topic, 030304 developmental biology, Aged, 0303 health sciences, business.industry, Brain Neoplasms, Case-control study, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Parotid gland, medicine.anatomical_structure, Logistic Models, Oncology, 030220 oncology & carcinogenesis, Meta-analysis, Case-Control Studies, Immunology, Hay fever, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, business
Abstract

A history of allergy has been inversely associated with several types of cancer although the evidence is not entirely consistent. We examined the association between allergy history and risk of glioma, meningioma, acoustic neuroma, and parotid gland tumors using data on a large number of cases and controls from five INTERPHONE study countries (Australia, Canada, France, Israel, New Zealand), to better understand potential sources of bias in brain tumor case–control studies and to examine associations between allergy and tumor sites where few studies exist. A total of 793 glioma, 832 meningioma, 394 acoustic neuroma, and 84 parotid gland tumor cases were analyzed with 2,520 controls recruited during 2000–2004. Conditional logistic regression models were used to obtain odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between self-reported allergy and tumor risk. A significant inverse association was observed between a history of any allergy and glioma (OR = 0.73, 95 % CI 0.60–0.88), meningioma (OR = 0.77, 95 % CI 0.63–0.93), and acoustic neuroma (OR = 0.64, 95 % CI 0.49–0.83). Inverse associations were also observed with specific allergic conditions. However, inverse associations with asthma and hay fever strengthened with increasing age of allergy onset and weakened with longer time since onset. No overall association was observed for parotid gland tumors (OR = 1.21, 95 % CI 0.73–2.02). While allergy history might influence glioma, meningioma, and acoustic neuroma risk, the observed associations could be due to information or selection bias or reverse causality.

Published
2012
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30. Acoustic neuroma risk in relation to mobile telephone use: results of the INTERPHONE international case-control study

Author

L. Montestruq, Gabriele Berg-Beckhoff, Anthony J. Swerdlow, N Yamaguchi, Maria Blettner, Joachim Schüz, Neil Pearce, Louise Nadon, Anna Lahkola, C. Johansen, Daniel Krewski, Bruce K. Armstrong, Anne-Sophie Evrard, Tore Tynes, Monika Moissonnier, J Siemiatycki, Ivano Iavarone, Anders Ahlbom, Avital Jarus-Hakak, Martine Vrijheid, M. Bernard, K. G. Blaasaas, Alistair Woodward, S. J. Hepworth, Salminen T, Isabelle Deltour, J Brown, Elisabeth Cardis, Martine Hours, Angela Chetrit, Päivi Kurttio, Patricia A. McKinney, Sigrid Lönn, Maria Feychting, Lars Klaeboe, Siegal Sadetzki, Brigitte Schlehofer, Helle Collatz Christensen, Toru Takebayashi, Interphone Study Grp, Susanna Lagorio, Anssi Auvinen, G.G. Giles, Angus Cook, M. M McBride, Minouk J. Schoemaker, Marie-Élise Parent, Kenneth Muir, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), International Agency for Cancer Research (IACR), IMIM-Hospital del Mar, Generalitat de Catalunya, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Sydney Cancer Centre and School of Public Health, The University of Sydney, Cancer Epidemiology Centre, The Cancer Council Victoria, School of Public Health and Hospital Research Center, Centre for Population Health Risk Assessment, University of Ottawa [Ottawa], Cancer Research Centre, BC Cancer Agency (BCCRC), Danish Cancer Society, Institute of Cancer Epidemiology, Radiation and Nuclear Safety Authority [Helsinki] (STUK), Département Transport, Santé, Sécurité (IFSTTAR/TS2), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université de Lyon, Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg - Universität Mainz (JGU), Department of Epidemiology and International Public Health, Universität Bielefeld = Bielefeld University-Faculty of Public Health, Unit of Environmental Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Cancer & Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, National Centre for Epidemiology Surveillance and Health Promotion, National Institute of Health, Department of Preventive Medicine and Public Health, University School of Medicine, Department of Public Health, University of Otago [Dunedin, Nouvelle-Zélande], Norwegian Radiation Protection Authority, The Cancer Registry of Norway, Norwegian Armed Forces Medical Services, The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], University of Leeds, The Health Science Research Institute, University of Warwick [Coventry], Institute of Cancer Research, Institute of cancer research, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, This work was supported by funding from the European Fifth Framework Program, ‘Quality of Life and Management of Living Resources’ (contract QLK4-CT-1999901563) and the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers’ Forum and GSM Association. Provision of funds to the INTERPHONE study investigators via the UICC was governed by agreements that guaranteed INTERPHONE's complete scientific independence. The terms of these agreements are publicly available at http://www.iarc.fr/en/research-groups/RAD/RCAd.html.The Australian centre was supported by the Australian National Health and Medical Research Council (EME Grant 219129) with funds originally derived from mobile phone service licence fees, Julianne Brown was partly supported by an Australian Postgraduate Award. Cancer Council NSW and Cancer Council Victoria provided most of the infrastructure for the project in Australia.The Canadian centres in Ottawa/Vancouver were supported by a university–industry partnership grant from the Canadian Institutes of Health Research (CIHR), the latter including partial support from the Canadian Wireless Telecommunications Association. The CIHR university–industry partnerships program also includes provisions that ensure complete scientific independence of the investigators. D. Krewski is the Natural Sciences and Engineering Research Council of Canada Chair in Risk Science at the University of Ottawa.The Canada – Montreal study was primarily funded by a grant from the Canadian Institutes of Health Research (project 15 MOP-42525). Additionally, Dr Siemiatycki's research team was partly funded by the Canada Research Chair programme and by the Guzzo-CRS Chair in Environment and Cancer. Dr Parent had a salary award from the Fonds de la recherche en santé du Québec.Additional funding for the study in France was provided by l’Association pour la Recherche sur le Cancer (ARC) [Contrat No. 5142] and three network operators (Orange, SFR, Bouygues Télécom). The funds provided by the operators represented 5% of the total cost of the French study and were governed by contracts guaranteeing the complete scientific independence of the investigators.The Finnish Interphone study received additional national funding from Emil Aaltonen Foundation and Academy of Finland (Grant No. 80921).The German Interphone study received additional national funding from the 'Deutsches Mobilfunkforschungsprogramm [German Mobile Phone Research Program]' of the German Federal Ministry of Environment, Nuclear Safety, and Nature Protection, the Ministry of Environment and Traffic of the state of Baden-Württemberg, the Ministry of Environment of the state of North Rhine-Westphalia, and the MAIFOR Programme of the University of Mainz.The Japanese Interphone study was fully funded by the Ministry of Internal Affairs and Communications of Japan.Funding in New Zealand for this project was provided by the Health Research Council of New Zealand, the Cancer Society of New Zealand, the Wellington Medical Research Foundation, the Hawke's Bay Medical Research Foundation and the Waikato Medical Research Foundation.The Swedish centre was additionally supported by the Swedish Research Council and the Swedish Cancer Society.The UK North study received additional funding from the Health and Safety Executive, the Department of Health, the Mobile Telecommunications, Health and Research (MTHR) program, and the Scottish Executive. The University of Leeds received some financial support on behalf of the 4 centres of the ‘UK North Study’ from the UK Network Operators (O2, Orange, T-Mobile, Vodafone, ‘3’) under legal signed contractual agreements which guaranteed complete independence for the scientific investigators.The Southeast England Centre wishes to acknowledge additional funding from the Mobile Telecommunications, Health and Research (MTHR) programme. The views expressed in this publication are those of the authors and not necessarily of the funders., and The INTERPHONE Study Group

Subjects
Male, Cancer Research, MESH: Neoplasms, Radiation-Induced, Neoplasms, Radiation-Induced, Epidemiology, MESH: Electromagnetic Fields, Decile, MESH: Glioma, 0302 clinical medicine, Risk Factors, Phone, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Meningeal Neoplasms, Odds Ratio, Medicine, Mobile phones, MESH: Middle Aged, Brain Neoplasms, Brain tumour, Glioma, Neuroma, Acoustic, MESH: Follow-Up Studies, Middle Aged, Prognosis, MESH: Case-Control Studies, 3. Good health, Survival Rate, Oncology, Reporting bias, 030220 oncology & carcinogenesis, Censoring (clinical trials), MESH: Brain Neoplasms, Female, Adult, MESH: Survival Rate, Acoustic neuroma, Radiofrequency electromagnetic fields, MESH: Prognosis, MESH: International Agencies, 03 medical and health sciences, Electromagnetic Fields, Vestibular schwannoma, Humans, MESH: Humans, business.industry, International Agencies, MESH: Adult, Odds ratio, medicine.disease, MESH: Meningeal Neoplasms, Confidence interval, MESH: Male, MESH: Odds Ratio, MESH: Cellular Phone, Mobile phone, Case-Control Studies, business, MESH: Female, Cell Phone, 030217 neurology & neurosurgery, Follow-Up Studies, Demography, MESH: Neuroma, Acoustic
Abstract

Background: The rapid increase in mobile telephone use has generated concern about possible health risks of radiofrequency electromagnetic fields from these devices. Methods: A case-control study of 1105 patients with newly diagnosed acoustic neuroma (vestibular schwannoma) and 2145 controls was conducted in 13 countries using a common protocol. Past mobile phone use was assessed by personal interview. In the primary analysis, exposure time was censored at one year before the reference date (date of diagnosis for cases and date of diagnosis of the matched case for controls); analyses censoring exposure at five years before the reference date were also done to allow for a possible longer latent period. Results: The odds ratio (OR) of acoustic neuroma with ever having been a regular mobile phone user was 0.85 (95% confidence interval 0.69-1.04). The OR for >= 10 years after first regular mobile phone use was 0.76 (0.52-1.11). There was no trend of increasing ORs with increasing cumulative call time or cumulative number of calls, with the lowest OR (0.48 (0.30-0.78)) observed in the 9th decile of cumulative call time. In the 10th decile (>= 1640 h) of cumulative call time, the OR was 1.32 (0.88-1.97); there were, however, implausible values of reported use in those with >= 1640 h of accumulated mobile phone use. With censoring at 5 years before the reference date the OR for >= 10 years after first regular mobile phone use was 0.83 (0.58-1.19) and for >= 1640 h of cumulative call time it was 2.79(1.51-5.16). but again with no trend in the lower nine deciles and with the lowest OR in the 9th decile. In general, ORs were not greater in subjects who reported usual phone use on the same side of the head as their tumour than in those who reported it on the opposite side, but it was greater in those in the 10th decile of cumulative hours of use. Conclusions: There was no increase in risk of acoustic neuroma with ever regular use of a mobile phone or for users who began regular use 10 years or more before the reference date. Elevated odds ratios observed at the highest level of cumulative call time could be due to chance, reporting bias or a causal effect. As acoustic neuroma is usually a slowly growing tumour, the interval between introduction of mobile phones and occurrence of the tumour might have been too short to observe an effect, if there is one. (C) 2011 Elsevier Ltd. All rights reserved.

Published
2011
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31. Risk of brain tumours in relation to estimated RF dose from mobile phones: results from five Interphone countries

Author

Lynne D. Richardson, Elisabeth Cardis, Martine Vrijheid, Alistair Woodward, Graham G. Giles, Rodrigo Villegas, Jordi Figuerola, Marie-Élise Parent, Daniel Krewski, Bruce K. Armstrong, Martine Hours, Julianne Brown, Avital Jarus-Hakak, L. Montestruq, Louise Nadon, Angela Chetrit, Chen Hoffmann, Siegal Sadetzki, Mary L. McBride, Joseph D. Bowman, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Sydney School of Public Health, The University of Sydney, Engineering and Physical Hazards Branch, National Institute for Occupational Safety and Health, Cancer Epidemiology Centre, Cancer Council Victoria, Centre for MEGA Epidemiology, University of Melbourne-School of Population Health, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), McLaughlin Centre for Population Health Risk Assessment, University of Ottawa [Ottawa], BC Cancer Research Centre, BC Cancer Agency (BCCRC), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Cancer and Radiation Epidemiology Unit, Chaim Sheba Medical Center-Gertner Institute, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], School of Population Health, University of Auckland [Auckland], Department of Diagnostic Imaging, Chaim Sheba Medical Center, Department of Population health, Hospital Research Centre-University of Montreal, Funding for the Interphone Study was provided by the European Fifth Framework Program, 'Quality of Life and Management of Living Resources' (contract QLK4-CT-1999901563), the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers' Forum and GSM Association. Provision of funds to the Interphone Study investigators via the UICC was governed by agreements that guaranteed Interphone's complete scientific independence. The terms of these agreements are publicly available at http://www.iarc.fr/en/research-groups/RAD/RCAd.html Specific additional funds were provided for the development and analysis of the radio frequency exposure gradient and by the Fondation Santé et Radiofréquences, France and the Bundesamt fuer Strahlenschutz, Germany. The Australian centre was supported by the National Health and Medical Research Council (EME grant 219129), and BKA was supported by the University of Sydney Medical Foundation Program Grant and Julianne Brown by an Australian Postgraduate Award. The Cancer Council NSW and the Cancer Council Victoria provided most of the infrastructure for the project in Australia. The Canada-Montréal data collection was funded by a grant from the Canadian Institutes of Health Research (project MOP-42525). Additionally, Dr Siemiatycki's research team was partly funded by the Canada Research Chair programme and by the Guzzo-CRS Chair in Environment and Cancer. Dr. Parent had salary support from the Fonds de recherche en santé du Québec. The other Canadian centres were supported by a universityeindustry partnership grant from the Canadian Institutes of Health Research (CIHR), the latter including partial support from the Canadian Wireless Telecommunications Association. The CIHR universityeindustry partnerships program also includes provisions that ensure complete scientific independence of the investigators. DK is the NSERC/SSHRC/McLaughlin Chair in Population Health Risk Assessment at the University of Ottawa. Additional funding for the study in France was provided by l'Association pour la Recherche sur le Cancer (ARC) (contract 5142) and three network operators (Orange, SFR, Bouygues Télécom). The funds provided by the operators represented 5% of the total cost of the French study and were governed by contracts guaranteeing the complete scientific independence of the investigators. In New Zealand, funding was provided by the Health Research Council, Hawkes Bay Medical Research Foundation and the Cancer Society of New Zealand. The findings and conclusions in this paper have not been formally disseminated by the National Institute for Occupational Safety and Health and should not be construed to represent any agency determination or policy.

Subjects
Oncology, Male, epidemiological study, MESH: Neoplasms, Radiation-Induced, Neoplasms, Radiation-Induced, Radio Waves, non-ionising radiation, MESH: Logistic Models, MESH: Meningioma, MESH: Radio Waves, MESH: Electromagnetic Fields, MESH: Glioma, 0302 clinical medicine, MESH: New Zealand, MESH: Risk Factors, Mobile phones, 030212 general & internal medicine, MESH: Middle Aged, ionising radiation, Brain Neoplasms, MESH: Israel, risk assessment, Brain, MESH: Case-Control Studies, RF exposure assessment, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Original Article, epidemiology, Female, physics, Algorithms, electromagnetic fields, medicine.medical_specialty, MESH: Radiation Dosage, Rf exposure, MESH: Australia, MESH: Algorithms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiation Dosage, Meningioma, 03 medical and health sciences, MESH: Canada, Glioma, Internal medicine, medicine, cancer, Humans, MESH: Humans, business.industry, MESH: Time Factors, Public Health, Environmental and Occupational Health, Case-control study, MESH: Adult, Odds ratio, medicine.disease, MESH: Meningeal Neoplasms, hygiene/occupational hygiene, MESH: Male, MESH: Odds Ratio, Surgery, nervous system diseases, MESH: France, Increased risk, Multicenter study, MESH: Cellular Phone, business, MESH: Female, Cell Phone
Abstract

International audience; OBJECTIVES: The objective of this study was to examine the associations of brain tumours with radio frequency (RF) fields from mobile phones. METHODS: Patients with brain tumour from the Australian, Canadian, French, Israeli and New Zealand components of the Interphone Study, whose tumours were localised by neuroradiologists, were analysed. Controls were matched on age, sex and region and allocated the 'tumour location' of their matched case. Analyses included 553 glioma and 676 meningioma cases and 1762 and 1911 controls, respectively. RF dose was estimated as total cumulative specific energy (TCSE; J/kg) absorbed at the tumour's estimated centre taking into account multiple RF exposure determinants. RESULTS: ORs with ever having been a regular mobile phone user were 0.93 (95% CI 0.73 to 1.18) for glioma and 0.80 (95% CI 0.66 to 0.96) for meningioma. ORs for glioma were below 1 in the first four quintiles of TCSE but above 1 in the highest quintile, 1.35 (95% CI 0.96 to 1.90). The OR increased with increasing TCSE 7+ years before diagnosis (p-trend 0.01; OR 1.91, 95% CI 1.05 to 3.47 in the highest quintile). A complementary analysis in which 44 glioma and 135 meningioma cases in the most exposed area of the brain were compared with gliomas and meningiomas located elsewhere in the brain showed increased ORs for tumours in the most exposed part of the brain in those with 10+ years of mobile phone use (OR 2.80, 95% CI 1.13 to 6.94 for glioma). Patterns for meningioma were similar, but ORs were lower, many below 1.0. CONCLUSIONS: There were suggestions of an increased risk of glioma in long-term mobile phone users with high RF exposure and of similar, but apparently much smaller, increases in meningioma risk. The uncertainty of these results requires that they be replicated before a causal interpretation can be made.

Published
2011
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32. A treelet transform analysis to relate nutrient patterns to the risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author

Eva Ardanaz, Maria Santucci de Magistris, Stefano Monni, Julie A. Schmidt, Rosario Tumino, Pietro Ferrari, Tonje Braaten, Nicholas J. Wareham, Sven Knueppel, Ingegerd Johansson, Christina C. Dahm, Anne Tjønneland, Timothy J. Key, Veronique Chajes, Christina Bamia, Laure Dossus, Nada Assi, Isabelle Romieu, Heinz Freisling, Ruth C. Travis, H. Bas Bueno de Mesquita, Rudolf Kaaks, Petra H.M. Peeters, Leila Lujan-Barroso, Jana Förster, Anja Olsen, Diego Salmerón, Kim Overvad, Nadia Slimani, José Ramón Quirós, Giovanna Masala, Elio Riboli, Pilar Amiano, Kay-Tee Khaw, Agnès Fournier, Claudia Agnoli, Marije F. Bakker, Vivian Viallon, Renée T. Fortner, Fulvio Ricceri, Philippos Orfanos, Esther Molina-Montes, Guri Skeie, Aurelie Moskal, Elisabete Weiderpass, Anna Winkvist, Antonia Trichopoulou, Laura Baglietto, Melissa A. Merritt, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany, parent, Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), CIBER de Epidemiología y Salud Pública (CIBERESP), Escuela Andaluza de Salud Publica, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain, Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain, Public Health Directorate, Asturias, Oviedo, Spain, Danish Cancer Society Research Center, Copenhagen, Denmark, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris Sud, UMRS, Villejuif, France, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Australia, Hellenic Health Foundation, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece, AOU Federico II, Naples, Italy, ISPO, Florence, Italy, IRCCS, Istituto Nazionale dei Tumori, Milan, Italy, CERMS, Turin, Italy, Civile - M.P.Arezzo Hospital, Imperial College London, London, and University Medical Center [Utrecht]

Subjects
Gerontology, Mediterranean diet, endocrine system diseases, ALCOHOL-CONSUMPTION, principal component analysis, Medicine (miscellaneous), Disease, EPIC, DISEASE, VDP::Medical disciplines: 700::Health sciences: 800::Nutrition: 811, 0302 clinical medicine, Nutrient, Breast cancer, Risk Factors, 030212 general & internal medicine, Prospective cohort study, Càncer, Non-U.S. Gov't, Public, Environmental & Occupational Health, Cancer, 2. Zero hunger, European Prospective Investigationinto Cancer and Nutrition, Nutrition and Dietetics, Research Support, Non-U.S. Gov't, ASSOCIATION, 11 Medical And Health Sciences, nutrient patterns, Middle Aged, Research Papers, CANCER, European Prospective Investigation into Cancer and Nutrition, TOTAL-ENERGY INTAKE, DIETARY PATTERNS, MEDITERRANEAN DIET, Europe, Receptors, Estrogen, 030220 oncology & carcinogenesis, NUTRITION, Female, Public Health, Menopause, Receptors, Progesterone, Life Sciences & Biomedicine, PROJECT, Adult, EPIDEMIOLOGIE, Principal component analysis, Pattern analysis, Breast Neoplasms, Research Support, Diet Surveys, EUROPEAN PROSPECTIVE INVESTIGATION, Nutrient patterns, VDP::Medisinske Fag: 700::Helsefag: 800::Ernæring: 811, 03 medical and health sciences, breast cancer, medicine, Journal Article, Humans, Treelet transform, Nutrició, METAANALYSIS, Proportional Hazards Models, Public Health, Environmental and Occupational Health, Nutrition, Science & Technology, Nutrition & Dietetics, business.industry, Environmental and Occupational Health, nutritional and metabolic diseases, WOMENS HEALTH, Feeding Behavior, medicine.disease, Diet, PROSPECTIVE COHORT, treelet transform, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Food Habits, business
Abstract

ObjectivePattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology.DesignNutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison.SettingThe European Prospective Investigation into Cancer and Nutrition (EPIC).SubjectsWomen (n 334 850) from the EPIC study.ResultsThe first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in β-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0·89, 95 % CI 0·83, 0·95, PtrendQ5 v. Q1=0·89, 95 % CI 0·81, 0·98, Ptrend=0·02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0·87, 95 % CI 0·77, 0·98, PtrendConclusionsTT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.

Published
2016
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33. Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study.

Author

O'Driscoll J, Burton A, Maskarinec G, Perez-Gomez B, Vachon C, Miao H, Lajous M, López-Ridaura R, Eliassen AH, Pereira A, Garmendia ML, Tamimi RM, Bertrand K, Kwong A, Ursin G, Lee E, Qureshi SA, Ma H, Vinnicombe S, Moss S, Allen S, Ndumia R, Vinayak S, Teo SH, Mariapun S, Fadzli F, Peplonska B, Nagata C, Stone J, Hopper JL, Giles G, Ozmen V, Aribal ME, Schüz J, Van Gils CH, Wanders JOP, Sirous R, Sirous M, Hipwell J, Kim J, Lee JW, Hartman M, Li J, Scott C, Chiarelli AM, Linton L, Pollan M, Flugelman AA, Salem D, Kamal R, Boyd N, Dos-Santos-Silva I, McCormack V, and Mullooly M

Subjects
Humans, Female, Middle Aged, Adult, Aged, Cross-Sectional Studies, Risk Factors, Aged, 80 and over, Parity, Body Mass Index, Breast Feeding, Pregnancy, Mammary Glands, Human abnormalities, Mammary Glands, Human diagnostic imaging, Breast Density, Mammography methods, Breast Neoplasms epidemiology, Breast Neoplasms diagnostic imaging, Breast Neoplasms etiology, Reproductive History
Abstract

Background: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD)., Methods: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest., Results: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (β: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (β: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (β:0.06, 95% CI:0.03, 0.10) and √DA (β:0.06, 95% CI:0.02, 0.10), and lower √NDA (β: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD., Conclusions: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk., (© 2024. The Author(s).)

Published
2024
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34. Correction to: Consumption of soft drinks and juices and risk of liver and biliary tract cancers in a European cohort.

Author

Stepien M, Duarte-Salles T, Fedirko V, Trichopoulou A, Lagiou P, Bamia C, Overvad K, Tjønneland A, Hansen L, Boutron-Ruault MC, Fagherazzi G, Severi G, Kühn T, Kaaks R, Aleksandrova K, Boeing H, Klinaki E, Palli D, Grioni S, Panico S, Tumino R, Naccarati A, Bueno-de-Mesquita HB, Peeters PH, Skeie G, Weiderpass E, Parr CL, Quirós JR, Buckland G, Molina-Montes E, Amiano P, Chirlaque MD, Ardanaz E, Sonestedt E, Ericson U, Wennberg M, Nilsson LM, Khaw KT, Wareham N, Bradbury KE, Ward HA, Romieu I, and Jenab M

Published
2024
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35. Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel.

Author

Levi H, Carmi S, Rosset S, Yerushalmi R, Zick A, Yablonski-Peretz T, Wang Q, Bolla MK, Dennis J, Michailidou K, Lush M, Ahearn T, Andrulis IL, Anton-Culver H, Antoniou AC, Arndt V, Augustinsson A, Auvinen P, Beane Freeman L, Beckmann M, Behrens S, Bermisheva M, Bodelon C, Bogdanova NV, Bojesen SE, Brenner H, Byers H, Camp N, Castelao J, Chang-Claude J, Chirlaque MD, Chung W, Clarke C, Collee MJ, Colonna S, Couch F, Cox A, Cross SS, Czene K, Daly M, Devilee P, Dork T, Dossus L, Eccles DM, Eliassen AH, Eriksson M, Evans G, Fasching P, Fletcher O, Flyger H, Fritschi L, Gabrielson M, Gago-Dominguez M, García-Closas M, Garcia-Saenz JA, Genkinger J, Giles GG, Goldberg M, Guénel P, Hall P, Hamann U, He W, Hillemanns P, Hollestelle A, Hoppe R, Hopper J, Jakovchevska S, Jakubowska A, Jernström H, John E, Johnson N, Jones M, Vijai J, Kaaks R, Khusnutdinova E, Kitahara C, Koutros S, Kristensen V, Kurian AW, Lacey J, Lambrechts D, Le Marchand L, Lejbkowicz F, Lindblom A, Loibl S, Lori A, Lubinski J, Mannermaa A, Manoochehri M, Mavroudis D, Menon U, Mulligan A, Murphy R, Nevelsteen I, Newman WG, Obi N, O'Brien K, Offit K, Olshan A, Plaseska-Karanfilska D, Olson J, Panico S, Park-Simon TW, Patel A, Peterlongo P, Rack B, Radice P, Rennert G, Rhenius V, Romero A, Saloustros E, Sandler D, Schmidt MK, Schwentner L, Shah M, Sharma P, Simard J, Southey M, Stone J, Tapper WJ, Taylor J, Teras L, Toland AE, Troester M, Truong T, van der Kolk LE, Weinberg C, Wendt C, Yang XR, Zheng W, Ziogas A, Dunning AM, Pharoah P, Easton DF, Ben-Sachar S, Elefant N, Shamir R, and Elkon R

Subjects
Humans, Female, Genome-Wide Association Study, Jews genetics, Israel epidemiology, Genetic Predisposition to Disease, Risk Factors, Multifactorial Inheritance genetics, Transcription Factors, Breast Neoplasms epidemiology, Breast Neoplasms genetics
Abstract

Background: Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women., Methods: We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel., Results: In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28)., Conclusions: Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women., Competing Interests: Competing interests: BCAC conflict of interest: MWB conducts research funded by Amgen, Novartis and Pfizer. PAF conducts research funded by Amgen, Novartis and Pfizer. He received Honoraria from Roche, Novartis and Pfizer. JV is one ofthe inventors of diagnosis and treatment of ERCC3-mutant cancer. AWK has a research funding for his institution from Myriad Genetics for an unrelated project (funding dates 2017–2019). UM has research collaborations with Mercy BioAnalytics, RNA Guardian, Dana Farber and iLOF (Intelligent Lab on Fiber). RAM is a consultant for Pharmavite., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Published
2023
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36. Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition.

Author

Yammine SG, Huybrechts I, Biessy C, Dossus L, Panico S, Sánchez MJ, Benetou V, Turzanski-Fortner R, Katzke V, Idahl A, Skeie G, Olsen KS, Tjønneland A, Halkjaer J, Colorado-Yohar S, Heath AK, Sonestedt E, Sartor H, Schulze MB, Palli D, Crous-Bou M, Dorronsoro A, Overvad K, Gurrea AB, Severi G, Vermeulen RCH, Sandanger TM, Travis RC, Key T, Amiano P, Van Guelpen B, Johansson M, Sund M, Tumino R, Wareham N, Sacerdote C, Krogh V, Brennan P, Riboli E, Weiderpass E, Gunter MJ, and Chajès V

Subjects
Humans, Female, Animals, Prospective Studies, Fatty Acids, Risk Factors, Diet adverse effects, gamma-Linolenic Acid, Endometrial Neoplasms epidemiology, Endometrial Neoplasms etiology
Abstract

Background: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons., Results: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintile Q5-Q1 =0.77, 95% CI = 0.64; 0.92, p trend =0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HR per unit increment =0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HR per unit increment = 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HR per unit increment = 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk., Conclusion: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer., (© 2023. The Author(s).)

Published
2023
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37. Associations between COVID-19 and hospitalisation with respiratory and non-respiratory conditions: a record linkage study.

Author

Rowe SL, Leder K, Dyson K, Sundaresan L, Wollersheim D, Lynch B, Abdullahi I, Cowie BC, Stephens N, Nolan TM, Sullivan SG, Sutton B, and Cheng AC

Subjects
Humans, COVID-19 Vaccines, SARS-CoV-2, Hospitalization, COVID-19 epidemiology, Myocardial Infarction
Abstract

Objectives: To assess associations between SARS-CoV-2 infection and the incidence of hospitalisation with selected respiratory and non-respiratory conditions in a largely SARS-CoV-2 vaccine-naïve population ., Design, Setting, Participants: Self-control case series; analysis of population-wide surveillance and administrative data for all laboratory-confirmed COVID-19 cases notified to the Victorian Department of Health (onset, 23 January 2020 - 31 May 2021; ie, prior to widespread vaccination rollout) and linked hospital admissions data (admission dates to 30 September 2021)., Main Outcome Measures: Hospitalisation of people with acute COVID-19; incidence rate ratios (IRRs) comparing incidence of hospitalisations with defined conditions (including cardiac, cerebrovascular, venous thrombo-embolic, coagulative, and renal disorders) from three days before to within 89 days of onset of COVID-19 with incidence during baseline period (60-365 days prior to COVID-19 onset)., Results: A total of 20 594 COVID-19 cases were notified; 2992 people (14.5%) were hospitalised with COVID-19. The incidence of hospitalisation within 89 days of onset of COVID-19 was higher than during the baseline period for several conditions, including myocarditis and pericarditis (IRR, 14.8; 95% CI, 3.2-68.3), thrombocytopenia (IRR, 7.4; 95% CI, 4.4-12.5), pulmonary embolism (IRR, 6.4; 95% CI, 3.6-11.4), acute myocardial infarction (IRR, 3.9; 95% CI, 2.6-5.8), and cerebral infarction (IRR, 2.3; 95% CI, 1.4-3.9)., Conclusion: SARS-CoV-2 infection is associated with higher incidence of hospitalisation with several respiratory and non-respiratory conditions. Our findings reinforce the value of COVID-19 mitigation measures such as vaccination, and awareness of these associations should assist the clinical management of people with histories of SARS-CoV-2 infection., (© 2022 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Published
2023
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38. The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

Author

Ward SV, Burton A, Tamimi RM, Pereira A, Garmendia ML, Pollan M, Boyd N, Dos-Santos-Silva I, Maskarinec G, Perez-Gomez B, Vachon C, Miao H, Lajous M, López-Ridaura R, Bertrand K, Kwong A, Ursin G, Lee E, Ma H, Vinnicombe S, Moss S, Allen S, Ndumia R, Vinayak S, Teo SH, Mariapun S, Peplonska B, Bukowska-Damska A, Nagata C, Hopper J, Giles G, Ozmen V, Aribal ME, Schüz J, Van Gils CH, Wanders JOP, Sirous R, Sirous M, Hipwell J, Kim J, Lee JW, Dickens C, Hartman M, Chia KS, Scott C, Chiarelli AM, Linton L, Flugelman AA, Salem D, Kamal R, McCormack V, and Stone J

Subjects
Adult, Cross-Sectional Studies, Female, Humans, Mammography methods, Menarche, Population Groups, Pregnancy, Risk Factors, Breast Density, Breast Neoplasms diagnostic imaging, Breast Neoplasms epidemiology, Breast Neoplasms etiology
Abstract

Background: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk., Methods: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche., Results: In pooled analyses, later age at menarche was associated with higher per cent density (β √PD  = 0.023 SE = 0.008, P = 0.003) and larger dense area (β √DA  = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (β √DA  = 0.069 SE = 0.028, P = 0.012) and higher per cent density (β √PD  = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups., Conclusions: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density., (© 2022. The Author(s).)

Published
2022
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39. Association of neighbourhood disadvantage and individual socioeconomic position with all-cause mortality: a longitudinal multicohort analysis.

Author

Ribeiro AI, Fraga S, Severo M, Kelly-Irving M, Delpierre C, Stringhini S, Kivimaki M, Joost S, Guessous I, Severi G, Giles G, Sacerdote C, Vineis P, and Barros H

Subjects
Cohort Studies, Humans, Smoking epidemiology, Socioeconomic Factors, Neighborhood Characteristics, Residence Characteristics
Abstract

Background: Few studies have examined the interactions between individual socioeconomic position and neighbourhood deprivation and the findings so far are heterogeneous. Using a large sample of diverse cohorts, we investigated the interaction effect of neighbourhood socioeconomic deprivation and individual socioeconomic position, assessed using education, on mortality., Methods: We did a longitudinal multicohort analysis that included six cohort studies participating in the European LIFEPATH consortium: the CoLaus (Lausanne, Switzerland), E3N (France), EPIC-Turin (Turin, Italy), EPIPorto (Porto, Portugal), Melbourne Collaborative Cohort Study (Melbourne, VIC, Australia), and Whitehall II (London, UK) cohorts. All participants with data on mortality, educational attainment, and neighbourhood deprivation were included in the present study. The data sources were the databases of each cohort study. Poisson regression was used to estimate the mortality rates and associations (relative risk, 95% CIs) with neighbourhood deprivation (Q1 being least deprived to Q5 being the most deprived). Baseline educational attainment was used as an indicator of individual socioeconomic position. Estimates were combined using pooled analysis and the relative excess risk due to the interaction was computed to identify additive interactions., Findings: The cohorts comprised a total population of 168 801 individuals. The recruitment dates were 2003-06 for CoLaus, 1989-91 for E3N, 1992-98 for EPIC-Turin, 1999-2003 for EPIPorto, 1990-94 for MCCS, and 1991-94 for Whitehall II. We use baseline data only and mortality data obtained using record linkage. Age-adjusted mortality rates were higher among participants residing in more deprived neighbourhoods than those in the least deprived neighbourhoods (Q1 least deprived neighbourhoods, 369·7 per 100 000 person-years [95% CI 356·4-383·2] vs Q5-most deprived neighbourhoods 445·7 per 100 000 person-years [430·2-461·7]), but the magnitude of the association varied according to educational attainment (relative excess risk due to interaction=0·18, 95% CI 0·08-0·28). The relative risk for Q5 versus Q1 was 1·31 (1·23-1·40) among individuals with primary education or less, but less pronounced among those with secondary education (1·12; 1·04-1·21) and tertiary education (1·16; 1·07-1·27). Associations remained after adjustment for individual-level factors, such as smoking, physical activity, and alcohol intake, among others., Interpretation: Our study suggests that the detrimental health effect of living in disadvantaged neighbourhoods is more pronounced among individuals with low education attainment, amplifying social inequalities in health. This finding is relevant to policies aimed at reducing health inequalities, suggesting that these issues should be addressed at both the individual level and the community level., Funding: The European Commission, European Regional Development Fund, the Portugese Foundation for Science and Technology., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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40. Diet Quality and Incident Non-Communicable Disease in the 1946-1951 Cohort of the Australian Longitudinal Study on Women's Health.

Author

Hlaing-Hlaing H, Dolja-Gore X, Tavener M, James EL, Hodge AM, and Hure AJ

Subjects
Adult, Australia epidemiology, Diet, Female, Humans, Longitudinal Studies, Middle Aged, Women's Health, Diet, Mediterranean, Noncommunicable Diseases epidemiology
Abstract

Diet quality indices (DQIs) can be useful predictors of diet-disease relationships, including non-communicable disease (NCD) multimorbidity. We aimed to investigate whether overall diet quality (DQ) predicted NCD, multimorbidity, and all-cause mortality. Women from the 1945-51 cohort of the Australia Longitudinal Study on Women's Health (ALSWH) were included if they: responded to S3 in 2001 and at least one survey between 2004 (S4) and 2016 (S8), and had no NCD history and complete dietary data at S3. DQ was summarized by the Healthy Eating Index for Australian Adults-2013 (HEIFA-2013), Mediterranean Diet Score (MDS), and Alternative Healthy Eating Index-2010 (AHEI-2010). Outcomes included each NCD (diabetes mellitus (DM), coronary heart disease (CHD), hypertension (HT), asthma, cancer (except skin cancer), depression and/or anxiety) independently, multimorbidity, and all-cause mortality. Repeated multivariate logistic regressions were used to test associations between DQIs and NCD outcomes across the 15 years of follow-up. The mean (±sd) of DQIs of participants ( n = 5350) were 57.15 ± 8.16 (HEIFA-2013); 4.35 ± 1.75 (MDS), and 56.01 ± 10.32 (AHEI-2010). Multivariate regressions indicated that women reporting the highest quintile of AHEI-2010 had lower odds of DM (42-56% (S5-S8)), HT (26% (S8)), asthma (35-37% (S7, S8)), and multimorbidity (30-35% (S7, S8)). The highest quintile of HEIFA-2013 and MDS had lower odds of HT (26-35% (S7, S8); 24-27% (S6-S8), respectively) and depression and/or anxiety (30% (S6): 30-34% (S7, S8)). Our findings support evidence that DQ is an important predictor of some NCDs and a target for prevention in middle-aged women.

Published
2021
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43. Life-course socioeconomic disadvantage and lung function: a multicohort study of 70 496 individuals.

Author

Rocha V, Fraga S, Moreira C, Carmeli C, Lenoir A, Steptoe A, Giles G, Goldberg M, Zins M, Kivimäki M, Vineis P, Vollenweider P, Barros H, and Stringhini S

Subjects
Adult, Aged, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Respiratory Function Tests, Risk Factors, Socioeconomic Factors, Vital Capacity, Lung
Abstract

Background: Lung function is an important predictor of health and a marker of physical functioning at older ages. This study aimed to quantify the years of lung function lost according to disadvantaged socioeconomic conditions across the life-course., Methods: This multicohort study used harmonised individual-level data from six European cohorts with information on life-course socioeconomic disadvantage and lung function assessed by forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC). 70 496 participants (51% female) aged 18-93 years were included. Socioeconomic disadvantage was measured in early life (low paternal occupational position), early adulthood (low educational level) and adulthood (low occupational position). Risk factors for poor lung function ( e.g. smoking, obesity, sedentary behaviour, cardiovascular and respiratory diseases) were included as potential mediators. The years of lung function lost due to socioeconomic disadvantage were computed at each life stage., Results: Socioeconomic disadvantage during the life-course was associated with a lower FEV 1 . By the age of 45 years, individuals experiencing disadvantaged socioeconomic conditions had lost 4-5 years of healthy lung function versus their more advantaged counterparts (low educational level -4.36 (95% CI -7.33--2.37) for males and -5.14 (-10.32--2.71) for females; low occupational position -5.62 (-7.98--4.90) for males and -4.32 (-13.31--2.27) for females), after accounting for the risk factors for lung function. By the ages of 65 years and 85 years, the years of lung function lost due to socioeconomic disadvantage decreased by 2-4 years, depending on the socioeconomic indicator. Sensitivity analysis using FVC yielded similar results to those using FEV 1 ., Conclusion: Life-course socioeconomic disadvantage is associated with lower lung function and predicts a significant number of years of lung function loss in adulthood and at older ages., Competing Interests: Conflict of interest: V. Rocha reports grants from Fundação para a Ciência e Tecnologia, during the conduct of the study. Conflict of interest: S. Fraga reports grants from Fundação para a Ciência e Tecnologia, during the conduct of the study. Conflict of interest: C. Moreira has nothing to disclose. Conflict of interest: C. Carmeli has nothing to disclose. Conflict of interest: A. Lenoir has nothing to disclose. Conflict of interest: A. Steptoe has nothing to disclose. Conflict of interest: G. Giles has nothing to disclose. Conflict of interest: M. Goldberg has nothing to disclose. Conflict of interest: M. Zins has nothing to disclose. Conflict of interest: M. Kivimäki reports grants from Medical Research Council, US National Institute on Aging, NordForsk, the Academy of Finland and Helsinki Institute of Life Science, during the conduct of the study. Conflict of interest: P. Vineis has nothing to disclose. Conflict of interest: P. Vollenweider has nothing to disclose. Conflict of interest: H. Barros has nothing to disclose. Conflict of interest: S. Stringhini reports grants from University of Lausanne, during the conduct of the study., (Copyright ©ERS 2021.)

Published
2021
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44. Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk.

Author

Kapoor PM, Mavaddat N, Choudhury PP, Wilcox AN, Lindström S, Behrens S, Michailidou K, Dennis J, Bolla MK, Wang Q, Jung A, Abu-Ful Z, Ahearn T, Andrulis IL, Anton-Culver H, Arndt V, Aronson KJ, Auer PL, Freeman LEB, Becher H, Beckmann MW, Beeghly-Fadiel A, Benitez J, Bernstein L, Bojesen SE, Brauch H, Brenner H, Brüning T, Cai Q, Campa D, Canzian F, Carracedo A, Carter BD, Castelao JE, Chanock SJ, Chatterjee N, Chenevix-Trench G, Clarke CL, Couch FJ, Cox A, Cross SS, Czene K, Dai JY, Earp HS, Ekici AB, Eliassen AH, Eriksson M, Evans DG, Fasching PA, Figueroa J, Fritschi L, Gabrielson M, Gago-Dominguez M, Gao C, Gapstur SM, Gaudet MM, Giles GG, González-Neira A, Guénel P, Haeberle L, Haiman CA, Håkansson N, Hall P, Hamann U, Hatse S, Heyworth J, Holleczek B, Hoover RN, Hopper JL, Howell A, Hunter DJ, John EM, Jones ME, Kaaks R, Keeman R, Kitahara CM, Ko YD, Koutros S, Kurian AW, Lambrechts D, Le Marchand L, Lee E, Lejbkowicz F, Linet M, Lissowska J, Llaneza A, MacInnis RJ, Martinez ME, Maurer T, McLean C, Neuhausen SL, Newman WG, Norman A, O'Brien KM, Olshan AF, Olson JE, Olsson H, Orr N, Perou CM, Pita G, Polley EC, Prentice RL, Rennert G, Rennert HS, Ruddy KJ, Sandler DP, Saunders C, Schoemaker MJ, Schöttker B, Schumacher F, Scott C, Scott RJ, Shu XO, Smeets A, Southey MC, Spinelli JJ, Stone J, Swerdlow AJ, Tamimi RM, Taylor JA, Troester MA, Vachon CM, van Veen EM, Wang X, Weinberg CR, Weltens C, Willett W, Winham SJ, Wolk A, Yang XR, Zheng W, Ziogas A, Dunning AM, Pharoah PDP, Schmidt MK, Kraft P, Easton DF, Milne RL, García-Closas M, and Chang-Claude J

Subjects
Aged, Aged, 80 and over, Body Mass Index, Breast Neoplasms metabolism, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Logistic Models, Medical History Taking, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Estrogen metabolism, Risk Factors, White People, Breast Neoplasms genetics
Abstract

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer., (© The Author(s) 2020. Published by Oxford University Press.)

Published
2021
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46. Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines.

Author

Vuong K, Armstrong BK, Drummond M, Hopper JL, Barrett JH, Davies JR, Bishop DT, Newton-Bishop J, Aitken JF, Giles GG, Schmid H, Jenkins MA, Mann GJ, McGeechan K, and Cust AE

Subjects
Adolescent, Australia epidemiology, Case-Control Studies, Humans, Risk Factors, Lentigo epidemiology, Melanoma diagnosis, Melanoma epidemiology, Melanoma etiology, Skin Neoplasms epidemiology, Skin Neoplasms etiology
Abstract

Background: Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk., Objectives: To develop and validate a model for incident first-primary cutaneous melanoma using clinically assessed risk factors., Methods: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case-Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole-body naevi and solar lentigines, and self-assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age- and sex-adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer-Lemeshow test., Results: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six-level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71-4·54] in the Australian study and 2·56 (95% CI 2·23-2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76-0·83) in the Australian study and 0·73 (95% CI 0·70-0·75) in the Leeds study. The Hosmer-Lemeshow test P-value was 0·30 in the Australian study and < 0·001 in the Leeds study., Conclusions: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self-assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically-assessed whole-body naevi and solar lentigines, and self-assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions., (© 2019 British Association of Dermatologists.)

Published
2020
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47. Declining use of radical prostatectomy and pelvic lymphadenectomy despite more robotics: National population data over 15 years.

Author

Roberts MJ, Papa N, Perera M, Joshi A, Scott S, Bolton D, Lawrentschuk N, and Yaxley J

Subjects
Aged, Aged, 80 and over, Humans, Male, Middle Aged, Retrospective Studies, Time Factors, United States, Lymph Node Excision methods, Prostatectomy methods, Robotics methods
Abstract

Aim: To describe national surgical patterns of prostate cancer (PCa) care considering radical prostatectomy with or without pelvic lymphadenectomy and consideration of robotic-assisted techniques., Methods: Retrospective analysis of publicly accessible Medicare claims data was performed for the period 2001-2016 and included patients undergoing radical prostatectomy with or without pelvic lymphadenectomy relative to total and PCa-specific populations among men aged 45-84 years. Proportion of cases performed robotically was considered., Results: Total procedures performed increased from 2001, peaked in 2009 and subsequently decreased until 2016. Since 2009, the age-specific rate of surgery in men aged 75-84 increased by 2.3-fold, whereas the rates for men aged 55-64 and 45-54 reduced by 44% and 55%, respectively. Rates of concurrent pelvic lymphadenectomy fell until 2009 with subsequent stabilization (ratio 1.05-1.14) through to 2016. Significant regional practice patterns were observed, as was an increasing trend toward a robotic-assisted laparoscopic approach, comprising more than 80% of radical prostatectomies in 2016., Conclusion: Since the peak in 2009, radical prostatectomy is performed less in men <65 years and more in men ≥65 years. An increasing proportion of cases omit concurrent pelvic lymphadenectomy and are performed robotically., (© 2019 John Wiley & Sons Australia, Ltd.)

Published
2020
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48. A New Comprehensive Colorectal Cancer Risk Prediction Model Incorporating Family History, Personal Characteristics, and Environmental Factors.

Author

Zheng Y, Hua X, Win AK, MacInnis RJ, Gallinger S, Marchand LL, Lindor NM, Baron JA, Hopper JL, Dowty JG, Antoniou AC, Zheng J, Jenkins MA, and Newcomb PA

Subjects
Adult, Aged, Colorectal Neoplasms diagnosis, Colorectal Neoplasms genetics, DNA Mismatch Repair genetics, Feasibility Studies, Female, Follow-Up Studies, Genetic Testing, Humans, Incidence, Male, Middle Aged, Mutation, ROC Curve, Registries statistics & numerical data, Risk Assessment methods, Risk Factors, Biomarkers, Tumor genetics, Colorectal Neoplasms epidemiology, Medical History Taking
Abstract

Purpose: Reducing colorectal cancer incidence and mortality through early detection would improve efficacy if targeted. We developed a colorectal cancer risk prediction model incorporating personal, family, genetic, and environmental risk factors to enhance prevention., Methods: A familial risk profile (FRP) was calculated to summarize individuals' risk based on detailed cancer family history (FH), family structure, probabilities of mutation in major colorectal cancer susceptibility genes, and a polygenic component. We developed risk models, including individuals' FRP or binary colorectal cancer FH, and colorectal cancer risk factors collected at enrollment using population-based colorectal cancer cases ( N = 4,445) and controls ( N = 3,967) recruited by the Colon Cancer Family Registry Cohort (CCFRC). Model validation used CCFRC follow-up data for population-based ( N = 12,052) and clinic-based ( N = 5,584) relatives with no cancer history at recruitment to assess model calibration [expected/observed rate ratio (E/O)] and discrimination [area under the receiver-operating-characteristic curve (AUC)]., Results: The E/O [95% confidence interval (CI)] for FRP models for population-based relatives were 1.04 (0.74-1.45) for men and 0.86 (0.64-1.20) for women, and for clinic-based relatives were 1.15 (0.87-1.58) for men and 1.04 (0.76-1.45) for women. The age-adjusted AUCs (95% CI) for FRP models for population-based relatives were 0.69 (0.60-0.78) for men and 0.70 (0.62-0.77) for women, and for clinic-based relatives were 0.77 (0.69-0.84) for men and 0.68 (0.60-0.76) for women. The incremental values of AUC for FRP over FH models for population-based relatives were 0.08 (0.01-0.15) for men and 0.10 (0.04-0.16) for women, and for clinic-based relatives were 0.11 (0.05-0.17) for men and 0.11 (0.06-0.17) for women., Conclusions: Both models calibrated well. The FRP-based model provided better risk stratification and risk discrimination than the FH-based model., Impact: Our findings suggest detailed FH may be useful for targeted risk-based screening and clinical management., (©2020 American Association for Cancer Research.)

Published
2020
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50. Comparing different definitions of prediabetes with subsequent risk of diabetes: an individual participant data meta-analysis involving 76 513 individuals and 8208 cases of incident diabetes.

Author

Lee CMY, Colagiuri S, Woodward M, Gregg EW, Adams R, Azizi F, Gabriel R, Gill TK, Gonzalez C, Hodge A, Jacobs Jr DR Jr, Joseph JJ, Khalili D, Magliano DJ, Mehlig K, Milne R, Mishra G, Mongraw-Chaffin M, Pasco JA, Sakurai M, Schreiner PJ, Selvin E, Shaw JE, Wittert G, Yatsuya H, and Huxley RR

Subjects
Biomarkers analysis, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 2 epidemiology, Disease Progression, Humans, Incidence, Prognosis, Risk Factors, Diabetes Mellitus, Type 1 pathology, Diabetes Mellitus, Type 2 pathology, Prediabetic State physiopathology
Abstract

Objective: There are currently five widely used definition of prediabetes. We compared the ability of these to predict 5-year conversion to diabetes and investigated whether there were other cut-points identifying risk of progression to diabetes that may be more useful., Research Design and Methods: We conducted an individual participant meta-analysis using longitudinal data included in the Obesity, Diabetes and Cardiovascular Disease Collaboration. Cox regression models were used to obtain study-specific HRs for incident diabetes associated with each prediabetes definition. Harrell's C-statistics were used to estimate how well each prediabetes definition discriminated 5-year risk of diabetes. Spline and receiver operating characteristic curve (ROC) analyses were used to identify alternative cut-points., Results: Sixteen studies, with 76 513 participants and 8208 incident diabetes cases, were available. Compared with normoglycemia, current prediabetes definitions were associated with four to eight times higher diabetes risk (HRs (95% CIs): 3.78 (3.11 to 4.60) to 8.36 (4.88 to 14.33)) and all definitions discriminated 5-year diabetes risk with good accuracy (C-statistics 0.79-0.81). Cut-points identified through spline analysis were fasting plasma glucose (FPG) 5.1 mmol/L and glycated hemoglobin (HbA1c) 5.0% (31 mmol/mol) and cut-points identified through ROC analysis were FPG 5.6 mmol/L, 2-hour postload glucose 7.0 mmol/L and HbA1c 5.6% (38 mmol/mol)., Conclusions: In terms of identifying individuals at greatest risk of developing diabetes within 5 years, using prediabetes definitions that have lower values produced non-significant gain. Therefore, deciding which definition to use will ultimately depend on the goal for identifying individuals at risk of diabetes., Competing Interests: Competing interests: CMYL, JAP, GW and RRH received grants from the National Health and Medical Research Council of Australia (NHMRC) during the conduct of the study; MW received person fees from Amgen and Hyowa Hakko Kirin outside the submitted work; RA received grants from NHMRC and the Hospital Research Foundation during the conduct of the study; JJJ received grants from National Institute of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (K23DK117041) during the conduct of the study; DJM and JES received grants from Commonwealth Department of Health and Aged Care, Abbott Australasia Pty Ltd, Alphapharm Pty Ltd, AstraZeneca, Aventis Pharmaceutical, Bristol-Myers Squibb Pharmaceuticals, Eli Lilly (Aust) Pty Ltd, GlaxoSmithKline, Janssen-Cilag (Aust) Pty Ltd, Merck Lipha s.a., Merck Sharp & Dohme (Aust), Novartis Pharmaceutical (Aust) Pty Ltd, Novo Nordisk Pharmaceutical Pty Ltd, Pharmacia and Upjohn Pty Ltd, Pfizer Pty Ltd, Sanofi Synthelabo, Servier Laboratories (Aust) Pty Ltd, the Australian Kidney Foundation and Diabetes Australia during the conduct of the study, and personal fees from AstraZeneca, Mylan, Boehringer Ingelheim, Sanofi, Merck Sharp and Dohme, Novo Nordisk and Eli Lilly outside the submitted work; PJS received grants from National Heart, Lung and Blood Institute during the conduct of the study; ES received grants from NIH during the conduct of the study., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Published
2019
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