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1. Predicted basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition

Author

Elisabete Weiderpass, Kim Overvad, Giovanna Masala, Guy Fagherazzi, Rudolf Kaaks, Daniel Redondo-Sánchez, Sabina Rinaldi, Ulrica Ericson, Dagfinn Aune, Pilar Amiano, Therese Haugdahl Nøst, Antonia Trichopoulou, Rosario Tumino, Paula Jakszyn, Neil Murphy, Elio Riboli, Tilman Kühn, Francesca Mancini, Heinz Freisling, Bas Bueno-de-Mesquita, Marie-Christine Boutron-Ruault, Maria Santucci de Magistris, Inge Huybrechts, Marc J. Gunter, Carlotta Sacerdote, Nathalie Kliemann, Christina C. Dahm, Vivian Viallon, Vittorio Krogh, Lena Maria Nilsson, Isabel Drake, Anne M. May, Heiner Boeing, Matthias B. Schulze, Carlo La Vecchia, Anne Tjønneland, Anna Karakatsani, Aurelio Barricarte Gurrea, Konstantinos K. Tsilidis, María Dolores Chirlaque, José Ramón Quirós, Centre international de Recherche sur le Cancer (CIRC), Université de Paris-Saclay [Villejuif], 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, Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A19170, 14136, C570/A16491 Ligue Contre le Cancer Bundesministerium für Bildung und Forschung, BMBF Bundesministerium für Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS Research Councils UK, RCUK Health and Medical Research Fund, HMRF: FIS Zorginstituut Nederland, ZIN PI13/01162, PI13/00061 World Cancer Research Fund, WCRF: ERC‐2009‐AdG 232997 Associazione Italiana per la Ricerca sul Cancro, AIRC National Research Council, NRC Ecumenical Project for International Cooperation, EPIC Institut National de la Santé et de la Recherche Médicale, Inserm European Commission, EU Centre International de Recherche sur le Cancer, CIRC Norway Deutsches Krebsforschungszentrum, DKFZ: DKFZ World Cancer Research Fund, WCRF Cancerfonden NordForsk Medical Research Council, MRC: MR/M012190/1, 1000143, The authors would like to thank the EPIC study participants and staff for their valuable contribution to this research. The authors would also like to thank Mr Bertrand Hemon for his support in preparing the databases and Dr Joseph Rothwell for his support in creating the figures. The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), 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 (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), ERC‐2009‐AdG 232997 and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS) of the Spanish Ministry of Health (FIS, PI13/00061 to Granada, PI13/01162 to EPIC‐Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), 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, and United Kingdom).

Subjects
Oncology, Adult, Male, metabolic disorder, Cancer Research, medicine.medical_specialty, obesity, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, medicine, Humans, cancer, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Prospective Studies, Risk factor, Càncer, Nutrició, Aged, Cancer, Nutrition, Sex Characteristics, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Metabolic disorder, Middle Aged, medicine.disease, Obesity, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Nutrition Assessment, 030220 oncology & carcinogenesis, Basal metabolic rate, basal metabolic rate, Female, Basal Metabolism, business
Abstract

Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1-standard deviation change in BMR [HR 1-SD]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR 1-SD: 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR 1-SD: 1.16; 95% CI 1.01; 1.35), pancreatic (HR 1-SD: 1.37; 95% CI 1.13; 1.66), thyroid (HR 1-SD: 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR 1-SD: 1.17; 95% CI 1.11; 1.22) and endometrial (HR 1-SD: 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.

Published
2020

2. Associations between exploratory dietary patterns and incident type 2 diabetes: a federated meta-analysis of individual participant data from 25 cohort studies

Author

Jannasch, Franziska, Dietrich, Stefan, Bishop, Tom RP, Pearce, Matthew, Fanidi, Anouar, O'Donoghue, Gráinne, O'Gorman, Donal, Marques-Vidal, Pedro, Vollenweider, Peter, Bes-Rastrollo, Maira, Byberg, Liisa, Wolk, Alicja, Hashemian, Maryam, Malekzadeh, Reza, Poustchi, Hossein, Luft, Vivian C, De Matos, Sheila M Alvim, Kim, Jihye, Kim, Mi Kyung, Kim, Yeonjung, Stern, Dalia, Lajous, Martin, Magliano, Dianna J, Shaw, Jonathan E, Akbaraly, Tasnime, Kivimaki, Mika, Maskarinec, Gertraud, Le Marchand, Loïc, Martínez-González, Miguel Ángel, Soedamah-Muthu, Sabita S, EPIC-InterAct Consortium, Wareham, Nicholas J, Forouhi, Nita G, Schulze, Matthias B, Medical and Clinical Psychology, Jannasch, Franziska [0000-0003-3478-4758], Apollo - University of Cambridge Repository, EPIC-InterAct Consortium, University of Cambridge [UK] (CAM), Université de Lausanne = University of Lausanne (UNIL), 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, G03/140, PI10/02293, PI10/02658, PI13/00615, PI14/01668, PI14/01764, PI14/01798, PI17/01795, PI20/00564, PNSD-2020/021, LSHM_CT_2006_037197, 82DZD00302, 122/2014, 27/2011, 45/2011, PNSD 2020/2021, FKZ: 01EA1806A, National Institutes of Health, NIH: R01AG056477, RF1AG062553, U01 CA164973, National Cancer Institute, NCI, American Institute for Cancer Research, AICR: 05B047, GlaxoSmithKline, GSK, Centre International de Recherche sur le Cancer, CIRC, Wellcome Trust, WT: 221854/Z/20/Z, Horizon 2020 Framework Programme, H2020: 824989, Seventh Framework Programme, FP7: 602068, Manchester Biomedical Research Centre, BRC: IS-BRC-1215-20014, Medical Research Council, MRC: MC_UU_00006/1and MC_UU_00006/3, Cancer Research UK, CRUK: C20/A5860, National Research Foundation, NRF, Department of Science and Technology, Ministry of Science and Technology, India, डीएसटी, Deutsche Forschungsgemeinschaft, DFG: 491394008, NFDI 13/1, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF: 33CS30-139468, 33CS30-148401, 33CS30_177535/1, 33CSCO-122661, MRCMR/R024227/1, Bundesministerium für Bildung und Forschung, BMBF, Consejo Nacional de Ciencia y Tecnología, CONACYT: S0008-2009-1: 000000000115312, Kementerian Sains, Teknologi dan Inovasi, MOSTI, Nederlandse Zuivel Organisatie, NZO, Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, Ministry of Science, ICT and Future Planning, MSIP: NRF-2017M3C9A6047623, Ministry of Health and Welfare, MOHW: 4845-301, 4851-302, Korea Centers for Disease Control and Prevention, KCDC, Seconda Università degli Studi di Napoli, SUN, Vetenskapsrådet, VR: 2017–00644, Universidad de Navarra, Tehran University of Medical Sciences and Health Services, TUMS: 81/15, Financiadora de Estudos e Projetos, FINEP: 01 06 0010.00, 01 06 0071.00, 01 06 0115.00, 01 06 0300.00, Ministério da Saúde, Mejeribrugets ForskningsFond, MFF, European Regional Development Fund, ERDF: RD 06/0045, Open Access funding enabled and organized by Projekt DEAL. The InterConnect project is funded by the European Union’s Seventh Framework Programme (grant number 602068). FJ and MBS acknowledge funding from the German Federal Ministry of Education and Research and the State of Brandenburg to the German Center for Diabetes Research (DZD) (82DZD00302). Furthermore, this work was supported by the NutriAct – Competence Cluster Nutrition Research Berlin-Potsdam funded by the German Federal Ministry of Education and Research (FKZ: 01EA1806A). This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491394008. This work was done as part of the NFDI4Health Consortium ( www.nfdi4health.de ). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – NFDI 13/1. NJW and NGF acknowledge funding from the Medical Research Council Epidemiology Unit (MC_UU_00006/1and MC_UU_00006/3) and NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014). NGF is an NIHR Senior Investigator (G111539). TB acknowledges funding from EUCAN-Connect under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 824989). The InterAct project was funded by the EU FP6 programme (grant number LSHM_CT_2006_037197). MBR and MAMG acknowledge that the SUN Project has received funding from the Spanish Government-Instituto de Salud Carlos III, and the European Regional Development Fund (FEDER) (RD 06/0045, CIBER-OBN, Grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, PI20/00564 and G03/140), PNSD-2020/021, the Navarra Regional Government (27/2011, 45/2011, 122/2014), PNSD 2020/2021, and the University of Navarra. LB and AW acknowledge that the COSM and SMC are part of the Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research, SIMPLER. SIMPLER receives funding through the Swedish Research Council (grant no 2017–00644). RM acknowledges funding from the Tehran University of Medical Sciences (grant number: 81/15), Cancer Research UK (grant number: C20/A5860), the Intramural Research Program of the U.S. National Cancer Institute, NIH, and the International Agency for Research on Cancer. SMAM and VCL acknowledge that ELSA-Brasil was supported by the Brazilian Ministry of Health (Department of Science and Technology) and Ministry of Science, Technology and Innovation (Financiadora de Estudos e Projetos (FINEP), grant numbers 01 06 0010.00, 01 06 0212.00, 01 06 0300.00, 01 06 0278.00, 01 06 0115.00 and 01 06 0071.00) and the National Council for Scientific and Technological Development (CNPq). JK acknowledges funding from the Korea Centers for Disease Control and Prevention, Ministry for Health and Welfare, Republic of Korea (4845-301 and 4851-302), and the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (NRF-2017M3C9A6047623). DS and ML acknowledge that this work of MTC was supported by the American Institute for Cancer Research (grant number 05B047) and the Consejo Nacional de Ciencia y Tecnología (CONACyT) (grant number S0008-2009-1: 000000000115312). LLM acknowledges funding from the US National Institutes of Health grant U01 CA164973, SSSM received the Wiebe Visser International Dairy Nutrition Prize and has received recent research funding (2019) for epidemiological studies on dairy products and cardiometabolic diseases from the Dutch Dairy Association and the Danish Dairy Research Foundation. PMV and PV acknowledge funding from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (grants 33CSCO-122661, 33CS30-139468, 33CS30-148401 and 33CS30_177535/1). MK and the Whitehall II study were supported by the UK Medical Research Council (MRCMR/R024227/1), the Wellcome Trust (221854/Z/20/Z) and the US National Institutes of Health (NIH, RF1AG062553, R01AG056477), during the conduct of the study. The funding sources did not participate in the design or conduct of the study, collection, management, analysis, or interpretation of the data, or preparation, review, or approval of the manuscript., We would like to thank the participants, principal investigators, and study teams of the individual cohorts included in this collaboration. The work presented herein was made possible using the OBiBa suite (http://www.obiba.org), a software suite developed by Maelstrom Research (www.maelstrom-research.org), and DataSHIELD (http://www.datashield.ac.uk), a software suite developed by the Data to Knowledge (D2K) Research Group. We thank EPIC-InterAct collaborators and Nicola Kerrison at the MRC Epidemiology Unit for assistance relating to the EPIC-InterAct dataset. We also thank the AusDiab Steering Committee for providing data from the AusDiab study. Moreover, we thank the NIH Biologic Specimen and Data Repository Information Coordinating Center and the ARIC, CARDIA, MESA, PRHHP and WHI OS study for providing data for this study., and HAL UVSQ, Équipe

Subjects
endocrine system diseases, Federated meta-analysis, Medicine (miscellaneous), BLOOD-PRESSURE, Endocrinology and Diabetes, PROFILE, Cohort Studies, Type 2 diabetes mellitus, Exploratory, Dietary patterns, DESIGN, Risk Factors, Humans, Prospective Studies, POPULATION, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, RISK, Diabetes Mellitus, Type 2/epidemiology, Diabetes Mellitus, Type 2/etiology, Diet, Incidence, Nutrition and Dietetics, OBJECTIVES, nutritional and metabolic diseases, CONSUMPTION, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Näringslära, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Diabetes Mellitus, Type 2, ATHEROSCLEROSIS, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Endokrinologi och diabetes, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, LIFE-STYLE, HEALTH, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Funder: Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE) (3440), PURPOSE: In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world. METHODS: This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis. RESULTS: 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRRpooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I2 = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRRpooled per 1 SD = 1.057, 95% CI 1.027-1.088). CONCLUSION: Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed.

Published
2022

3. Co-benefits from sustainable dietary shifts for population and environmental health: an assessment from a large European cohort study

Author

Manuela M. Bergmann, Tammy Y.N. Tong, Anna Stubbendorff, Elisabeth H. M. Temme, Claudia Agnoli, Ulrika Ericson, Antonio Agudo, Mélanie Deschasaux, Elisabete Weiderpass, Konstantinos K. Tsilidis, Dagfinn Aune, Guri Skeie, Giovanna Masala, Torkjel M. Sandanger, Emmanuelle Kesse-Guyot, Gianluca Severi, Charlotta Rylander, Francesca Mancini, Miguel A. Rodríguez Barranco, Marie-Christine Boutron-Ruault, Paolo Vineis, Mathilde Touvier, Pietro Ferrari, Marc J. Gunter, Daniel B Ibsen, Jolanda M. A. Boer, María José Pérez, Inge Huybrechts, Matthias B. Schulze, Anika Knuppel, Keren Papier, Elio Riboli, Bernard Srour, Christina C. Dahm, Jessica E. Laine, Tilmann Kühn, Medical Research Council (MRC), Imperial College London, University of Bern, Centre international de Recherche sur le Cancer (CIRC), Bjørknes University College [Oslo, Norvège], Oslo University Hospital [Oslo], University of Potsdam, German Institute of Human Nutrition Potsdam-Rehbruecke [Nuthetal, Germany] (GIHNP-R), National Institute for Public Health and the Environment [Bilthoven] (RIVM), IRCCS Istituto Nazionale dei Tumori [Milano], Lund University [Lund], Aarhus University [Aarhus], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Espace régional de réflexion éthique de Normandie (EREN), Escuela Andaluza de Salud Pública [Granada, Spain] (EASP), ibs.GRANADA Instituto de Investigación Biosanitaria [Granada, Spain], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Granada [Granada], University of Oxford [Oxford], 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, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Istituto per lo Studio, la Prevenzione e la rete Oncologica [Florence, Italy] (ISPRO), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), The Arctic University of Norway (UiT), Italian Institute of Technology (IIT), International Arctic Research Center, University of Alaska, Fairbanks, IARC, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Wellcome Trust, WT: 205212/Z/16/Z, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, MR/M501669/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, The coordination of EPIC is financially supported by IARC and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre. The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, INSERM (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund, Statistics Netherlands (The Netherlands), Health Research Fund - Instituto de Salud Carlos III, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), Medical Research Council (MRC, 1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford, UK). JEL was supported by an MRC Early Career Fellowship (MR/M501669/1). We acknowledge the Netherlands Cancer Registry and Statistics Netherlands (The Netherlands) for contributions to data acquisition. KP and AK are supported by the Wellcome Trust (Livestock, Environment and People, LEAP, grant number 205212/Z/16/Z). We acknowledge Corinne Casagrande and Genevieve Nicolas who assisted in the matching of the dietary intake data with the Greenhouse Gas and Landuse data. We also acknowledge Bertrand Hemon for database compilation and Carine Biessy for her contribution to the sensitivity analyses. Where authors are identified as personnel of the IARC or WHO, the authors alone are responsible for the views expressed in this Article and they do not necessarily represent the decisions, policy, or views of the IARC or WHO., Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, INSERM (France), Health Research Fund - Instituto de Salud Carlos III, Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), University of Potsdam = Universität Potsdam, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Universidad de Granada = University of Granada (UGR), Nuffield Department of Population Health [Oxford], University of Oxford, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Università degli Studi di Firenze = University of Florence (UniFI), Institut Gustave Roussy (IGR), The Arctic University of Norway [Tromsø, Norway] (UiT), European Commission (DG-SANCO), the International Agency for Research on Cancer (IARC), MRC Early Career Fellowship (MR/M501669/1), and HAL UVSQ, Équipe

Subjects
Health (social science), 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], Population, Medicine (miscellaneous), 610 Medicine & health, Population health, Cohort Studies, Greenhouse Gases, 03 medical and health sciences, Clinical trials, 0302 clinical medicine, 360 Social problems & social services, Environmental health, 11. Sustainability, Canvi climàtic, Humans, Medicine, VDP::Medisinske Fag: 700, Prospective Studies, 030212 general & internal medicine, education, 2. Zero hunger, Public health, 0303 health sciences, education.field_of_study, Land use, business.industry, Health Policy, Hazard ratio, Public Health, Environmental and Occupational Health, Salut pública, Climatic change, Diet, 3. Good health, European Prospective Investigation into Cancer and Nutrition, [SDV] Life Sciences [q-bio], VDP::Medical disciplines: 700, Quartile, 13. Climate action, Greenhouse gas, Attributable risk, Dieta, business, Environmental Health, Assaigs clínics
Abstract

Funding European Commission (DG-SANCO) , the International Agency for Research on Cancer (IARC) , MRC Early Career Fellowship (MR/M501669/1) ., Background Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas emissions, substantial land use, and adverse health such as cancer and mortality. To assess the potential co-benefits from shifting to more sustainable diets, we aimed to investigate the associations of dietary greenhouse gas emissions and land use with all-cause and cause-specific mortality and cancer incidence rates. Methods Using data from 443 991 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a multicentre prospective cohort, we estimated associations between dietary contributions to greenhouse gas emissions and land use and all-cause and cause-specific mortality and incident cancers using Cox proportional hazards regression models. The main exposures were modelled as quartiles. Co-benefits, encompassing the potential effects of alternative diets on all-cause mortality and cancer and potential reductions in greenhouse gas emissions and land use, were estimated with counterfactual attributable fraction intervention models, simulating potential effects of dietary shifts based on the EAT–Lancet reference diet. Findings In the pooled analysis, there was an association between levels of dietary greenhouse gas emissions and allcause mortality (adjusted hazard ratio [HR] 1·13 [95% CI 1·10–1·16]) and between land use and all-cause mortality (1·18 [1·15–1·21]) when comparing the fourth quartile to the first quartile. Similar associations were observed for cause-specific mortality. Associations were also observed between all-cause cancer incidence rates and greenhouse gas emissions, when comparing the fourth quartile to the first quartile (adjusted HR 1·11 [95% CI 1·09–1·14]) and between all-cause cancer incidence rates and land use (1·13 [1·10–1·15]); however, estimates differed by cancer type. Through counterfactual attributable fraction modelling of shifts in levels of adherence to the EAT–Lancet diet, we estimated that up to 19–63% of deaths and up to 10–39% of cancers could be prevented, in a 20-year risk period, by different levels of adherence to the EAT–Lancet reference diet. Additionally, switching from lower adherence to the EAT–Lancet reference diet to higher adherence could potentially reduce food-associated greenhouse gas emissions up to 50% and land use up to 62%. Interpretation Our results indicate that shifts towards universally sustainable diets could lead to co-benefits, such as minimising diet-related greenhouse gas emissions and land use, reducing the environmental footprint, aiding in climate change mitigation, and improving population health., European Commission European Commission Joint Research Centre, World Health Organization, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/M501669/1

Published
2021

4. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Author

Eva Ardanaz, Agnetha Linn Rostgaard-Hansen, Alessio Naccarati, Elisabete Weiderpass, Pekka Keski-Rahkonen, Rudolf Kaaks, Tilman Kühn, Anna Winkvist, Jośe Mariá Huerta, H. B. Bueno-De-Mesquita, Guri Skeie, Pietro Ferrari, Krasimira Aleksandrova, Gabriel Perlemuter, Augustin Scalbert, Olatz Mokoroa, Giovanna Tagliabue, Marc J. Gunter, Kim Overvad, José Ramón Quirós, Agneta Kiss, Marie-Christine Boutron-Ruault, Yahya Mahamat-Saleh, Talita Duarte-Salles, Nivonirina Robinot, Anne Tjønneland, Antonia Trichopoulou, Julie A. Schmidt, Christina C. Dahm, Roel Vermeulen, Rosario Tumino, Núria Sala, Joseph A. Rothwell, Sophia Harlid, Magdalena Stepien, Klas Sjöberg, Vivian Viallon, Neil Murphy, Anna Karakatsani, Salvatore Panico, Nicholas J. Wareham, María José Sánchez, Francesca Mancini, Domenico Palli, Mazda Jenab, Elio Riboli, Bodil Ohlsson, Kay-Tee Khaw, 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), Institut National Du Cancer, INCa: 2014-1-RT-02-CIRC-1 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Cancer Research UK, CRUK: C570/A16491 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS National Research Council, NRC 6236 Hellenic Health Foundation, HHF Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, CIRC Associazione Italiana per la Ricerca sul Cancro, AIRC RD06/0020 Deutsche Krebshilfe World Cancer Research Fund, WCRF Cancerfonden Medical Research Council, MRC: MR/M012190/1, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA) (grant number 2014-1-RT-02-CIRC-1, PI: M. Jenab). 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 Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (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), and Statistics Netherlands (the Netherlands), and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 for EPIC-Norfolk and C570/A16491 for EPIC-Oxford) and the Medical Research Council (1000143 for EPIC-Norfolk and MR/M012190/1 for EPIC-Oxford) (UK). The funding sources had no influence on the design of the study, the collection, analysis, and interpretation of data, the writing of the report, and or the decision to submit the paper for publication. Disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, prospective observational cohort, Glycocholic acid, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mass Spectrometry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dehydroepiandrosterone sulfate, Internal medicine, Biomarkers, Tumor, medicine, Humans, Metabolomics, Prospective Studies, Aged, Hepatitis, business.industry, Liver Neoplasms, Cancer, Feeding Behavior, hepatocellular carcinoma, Middle Aged, medicine.disease, 3. Good health, European Prospective Investigation into Cancer and Nutrition, untargeted metabolomics, chemistry, Case-Control Studies, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, Female, business, Metabolic Networks and Pathways, Chromatography, Liquid, Cohort study
Abstract

International audience; Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.

Published
2020

5. Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study

Author

Pietro Ferrari, Fulvio Ricceri, Christina C. Dahm, Kim Overvad, Sabina Sieri, Elisabete Weiderpass, Eleni Peppa, María José Sánchez, Leila Luján Barroso, Marta Solans Margalef, Matthias B. Schulze, Federico Canzian, Giovanna Masala, Florentin Spaeth, Dagfinn Aune, Roel Vermeulen, Tilman Kühn, Delphine Casabonne, Karin Jirstom, Anna Karakatsani, José María Huerta, Yahya Mahamat-Saleh, Paul Brennan, Cecilie Kyrø, Mats Jerkeman, Caroline Besson, Pilar Amiano Exezarreta, Virginia Menéndez, Elio Riboli, Julie A. Schmidt, Rosario Tumino, Sairah L.F. Chen, Marc J. Gunter, Eva Ardanaz, Antonia Trichopoulou, Alexandra Nieters, Marie-Christine Boutron-Ruault, Anne Tjønneland, Fatemeh Saberi Hosnijeh, Sabine Naudin, Salvatore Panico, Centre international de Recherche sur le Cancer (CIRC), 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), Centre Hospitalier de Versailles André Mignot (CHV), Direction Générale de la Compétitivité, de l’Industrie et des Services, DGCIS Food Standards Agency, FSA Cancer Research UK, CRUK: C864/A14136, C8221/A19170, C570/A16491 RD06/0020 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Université Claude Bernard Lyon 1, UCBL Wellcome Trust, WT Ligue Contre le Cancer 6236 German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Department of Health, Australian Government Ministry of Health and Social Solidarity, Greece Kræftens Bekæmpelse, DCS British Heart Foundation, BHF Instituto de Salud Carlos III, ISCIII National Research Council, NRC Mutuelle Générale de l'Education Nationale, MGEN Hellenic Health Foundation, HHF Stroke Association Institut National de la Santé et de la Recherche Médicale, Inserm Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, IARC Deutsche Krebshilfe Cancerfonden World Cancer Research Fund, WCRF Stavros Niarchos Foundation, SNF Ministère des Affaires Sociales et de la Santé: GR‐IARC‐2003‐09‐12‐01 Medical Research Council, MRC: MR/M012190/1, MR/N003284/1, MC‐UU_12015/1, We thank Carine Biessy and Bertrand Hemon for their technical support and contribution to this work. We are also grateful to all the EPIC participants who have been part of the project and to the many other members of the study teams who have enabled this research. This work was supported by the Direction Générale de la Santé (French Ministry of Health, Grant GR‐IARC‐2003‐09‐12‐01), by the European Commission (Directorate General for Health and Consumer Affairs) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), the Ligue Contre le Cancer, the Institut Gustave Roussy, the Mutuelle Générale de l'Education Nationale and the Institut National de la Santé et de la Recherche Médicale (France), the Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, the World Cancer Research Fund and Statistics Netherlands (the Netherlands), the Health Research Fund, Regional Governments of Andalucýa, Asturias, Basque Country, Murcia (project 6236) and Navarra, Instituto de Salud Carlos III, Redes de Investigacion Cooperativa (RD06/0020, Spain), the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), Cancer Research UK (C864/A14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/N003284/1 and MC‐UU_12015/1 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, and United Kingdom), the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK). This work was part of Sabine Naudin's PhD at Claude Bernard Lyon I University (France), funded by Région Auvergne Rhône‐Alpes, ADR 2016 (France).

Subjects
Male, Oncology, Cancer Research, Lymphoma, Body Mass Index, 0302 clinical medicine, Risk Factors, immune system diseases, hemic and lymphatic diseases, Prospective Studies, Prospective cohort study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Incidence, non-Hodgkin lymphoma, Smoking, Hazard ratio, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, 030220 oncology & carcinogenesis, Female, EPIC, healthy lifestyle index, Hodgkin lymphoma, prospective study, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Alcohol Drinking, [SDV.CAN]Life Sciences [q-bio]/Cancer, Diet Surveys, 03 medical and health sciences, Internal medicine, REGRESSION, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Healthy Lifestyle, Exercise, Aged, Science & Technology, business.industry, Proportional hazards model, HODGKINS-LYMPHOMA, Feeding Behavior, medicine.disease, Confidence interval, Etiology, UPDATE, CIGARETTE-SMOKING, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Follow-Up Studies
Abstract

This is the peer reviewed version of the following article: Naudin, S., Margalef, M.S., Hosnijeh, F.S., Nieters, A., Kyrø, C. Tjønneland, A. ... Ferrari, P. (2020) Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study. International Journal of Cancer, 147(6):1649-1656, which has been published in final form at https://doi.org/10.1002/ijc.32977. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this work, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL) were evaluated in a large‐scale European prospective cohort. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases (132 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow‐up. The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, physical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox proportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI score. The HLI was inversely associated with HL, with HR for a 1‐standard deviation (SD) increment in the score equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly driven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1‐SD increment equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL subtypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.

Published
2020

6. Regression rate of choroidal melanoma following iodine-125 brachytherapy is not associated with metastatic spread

Author

Juliette Thariat, Frédéric Mouriaux, Anne-Sophie Julien, Solange Landreville, Ioana Fugaru, Nadia Lihimdi, François Pépin, Centre international de Recherche sur le Cancer (CIRC), Université Laval [Québec] (ULaval), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Vision Health Research Network (VHRN) from the Fonds de recherche du Quebec-Sante (FRQS, Uveal Melanoma Common Infrastructure), Fonds de recherche du Centre universitaire d'ophtalmologie du CHU de Quebec, Fondation du CHU de Quebec, Universite Laval, and Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Skin Neoplasms, [SDV]Life Sciences [q-bio], medicine.medical_treatment, brachytherapy, Brachytherapy, Urology, Dermatology, tumour regression, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Humans, metastasis, Medicine, choroidal melanoma, Stage (cooking), Melanoma, Survival rate, Retrospective Studies, ultrasound, Proportional hazards model, business.industry, Choroid Neoplasms, Mortality rate, Retrospective cohort study, Middle Aged, medicine.disease, Regression, 3. Good health, Survival Rate, 030104 developmental biology, Oncology, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Female, prognosis, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

International audience; Nearly half of choroidal melanomas progress to the metastatic stage at 15 years. The purpose of our study was to evaluate the prognostic value of tumour-height regression rate in medium-sized choroidal melanomas treated with iodine-125 brachytherapy. A retrospective cohort study was performed on 128 patients with medium-sized choroidal melanoma who were treated with iodine-125 brachytherapy. Tumour characteristics including tumour apical height at baseline and after irradiation, recurrence, metastasis and mortality were collected from patients' records. Regression rate was defined in mm/month or in percentage of baseline apical height. Patients were statistically stratified in three groups of regression rate at 6 months using the Ward's method and Euclidian distance (slow, medium and fast regression groups). Mean initial apical height was of 5.71±1.79 mm. At 6 months, the average regression rate was 0.02±0.12 mm/month in the slow group (n=60), 0.32±0.11 mm/month in the medium group (n=52) and 0.67±0.21 mm/month in the fast group (n=16). Cox regression analysis for the recurrence, metastasis and mortality rates according to the three groups did not show any statistically significant difference. Sensitivity analyses with the regression rates at 12 months showed similar associations. Exudative retinal detachment resolved with treatment at 5.9±4.0 months, and it was more common at presentation in the fast regression rate group. The regression rate at 6 and 12 months after iodine-125 brachytherapy is not associated with a higher metastatic rate in medium-sized choroidal melanoma.

Published
2019

7. The fraction of lung cancer incidence attributable to fine particulate air pollution in France: Impact of spatial resolution of air pollution models

Author

Isabelle Soerjomataram, Rémy Slama, Sylvia Medina, Alain Le Tertre, Barbara Charbotel, Ivana Kulhánová, Jean-Nicolas Ormsby, Xavier Morelli, Dana Loomis, Johanna Lepeule, Centre international de Recherche sur le Cancer (CIRC), Centre Léon Bérard [Lyon], Santé publique France - French National Public Health Agency [Saint-Maurice, France], 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), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Percentile, Lung Neoplasms, Population, Air pollution, FRANCE, [SDV.CAN]Life Sciences [q-bio]/Cancer, 010501 environmental sciences, medicine.disease_cause, complex mixtures, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, Environmental health, medicine, Humans, 030212 general & internal medicine, Lung cancer, education, lcsh:Environmental sciences, 0105 earth and related environmental sciences, General Environmental Science, Cause of death, lcsh:GE1-350, education.field_of_study, business.industry, Incidence, Incidence (epidemiology), LUNG CANCER, medicine.disease, [SDE.ES]Environmental Sciences/Environmental and Society, 3. Good health, AIR POLLUTION, 13. Climate action, Relative risk, Attributable risk, Particulate Matter, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, POPULATION ATTRIBUTABLE FRACTION
Abstract

Outdoor air pollution is a leading environmental cause of death and cancer incidence in humans. We aimed to estimate the fraction of lung cancer incidence attributable to fine particulate matter (PM2.5) exposure in France, and secondarily to illustrate the influence of the input data and the spatial resolution of information on air pollution levels on this estimate. The population attributable fraction (PAF) was estimated using a nationwide spatially refined chemistry-transport model with a 2-km spatial resolution, neighbourhood-scale population density data, and a relative risk from a published meta-analysis. We used the WHO guideline value for PM2.5 exposure (10 μg/m3) as reference. Sensitivity analyses consisted in attributing the nation-wide median exposure to all areas and using alternative input data such as reference of PM2.5 exposure level and relative risk. Population-weighted median PM2.5 level in 2005 was 13.8 μg/m3; 87% of the population was exposed above the guideline value. The burden of lung cancer attributable to PM2.5 exposure corresponded to 1466 cases, or 3.6% of all cases diagnosed in 2015. Sensitivity analyses showed that the use of a national median of PM2.5 exposure would have led to an underestimation of the PAF by 11% (population-weighted median) and by 72% (median of raw concentration), suggesting that our estimates would have been higher with even more finely spatially-resolved models. When the PM2.5 reference level was replaced by the 5th percentile of country-scale exposure (4.9 μg/m3), PAF increased to 7.6%. Other sensitivity analyses resulted in even higher PAFs. Improvements in air pollution are crucial for quantitative health impacts assessment studies. Actions to reduce PM2.5 levels could substantially reduce the burden of lung cancer in France. Keywords: Air pollution, Lung cancer, Population attributable fraction, France

Published
2018

8. A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC

Author

Ingegerd Johansson, David S. Lopez, Alicia K Heath, Amanda J. Cross, Anne Tjønneland, J. Ramón Quirós, Melissa A. Merritt, Paula Jakszyn, Bas Bueno-de-Mesquita, Pilar Amiano, Anne Kirstine Eriksen, Manuela M. Bergmann, Marc J. Gunter, Bernard Srour, David C. Muller, Piet A. van den Brandt, Matthias B. Schulze, Salvatore Panico, Claudia Agnoli, Pietro Ferrari, Marco Lukic, José María Huerta, Christina C. Dahm, Therese Haugdahl Nøst, Areti Papadopoulou, Aurelio Barricarte Gurrea, Rosario Tumino, María José Sánchez, Fulvio Ricceri, Nadia Bastide, Paolo Vineis, Ulrika Ericson, Eva Ardanaz, Gianluca Severi, Guri Skeie, Aurora Perez-Cornago, Nikos Papadimitriou, Emmanouil Bouras, Elisabete Weiderpass, Ellio Riboli, Ioanna Tzoulaki, Heiner Boeing, Stina Bodén, Giovanna Masala, Jeroen W.G. Derksen, Jonna Berntsson, Verena Katzke, Elena Critselis, Konstantinos K. Tsilidis, University of Ioannina, Maastricht University [Maastricht], Imperial College London, Biomedical Research Foundation of the Academy of Athens (BRFAA), International Agency for Cancer Research (IACR), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), 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, University of Hawai'i [Honolulu] (UH), The University of Texas Health Science Center at Houston (UTHealth), University of Oxford [Oxford], University of Potsdam, The Arctic University of Norway (UiT), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Umeå University, Università degli studi di Torino = University of Turin (UNITO), Lund University [Lund], Instituto de Salud Carlos III [Madrid] (ISC), Aarhus University [Aarhus], IRCCS Istituto Nazionale dei Tumori [Milano], University of Copenhagen = Københavns Universitet (KU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Naples Federico II, La Salle [Ramon Llull University], Utrecht University [Utrecht], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, International Council of Ophthalmology, ICO, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF: WCRF 2014/1180, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Funding This work was supported by the World Cancer Research Fund International Regular Grant Programme (WCRF 2014/1180 to Konstantinos K. Tsilidis). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the National Institute for Health Research Imperial Biomedical Research Centre. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo 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)?Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (ICO) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford) and Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., Funding This work was supported by the World Cancer Research Fund International Regular Grant Programme ( WCRF 2014/1180 to Konstantinos K. Tsilidis). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the National Institute for Health Research Imperial Biomedical Research Centre . The national cohorts are supported by the Danish Cancer Society (Denmark), 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 ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research ( BMBF ) (Germany), 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)– Instituto de Salud Carlos III ( ISCIII ), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology ( ICO ) (Spain), Swedish Cancer Society , Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Epidemiologie, and RS: GROW - R1 - Prevention

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Riboflavin, colorectal cancer, Lower risk, Cohort Studies, Animal science, beta-Carotene, Risk Factors, Epidemiology, medicine, cohort study, Humans, Prospective Studies, Hepatology, Gastroenterology & Hepatology, business.industry, Hazard ratio, Gastroenterology, food and beverages, 1103 Clinical Sciences, Confidence interval, European Prospective Investigation into Cancer and Nutrition, Diet, epidemiology, nutrition, business, Colorectal Neoplasms, Cohort study
Abstract

Background & Aims: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. Methods: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. Results: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04–1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04–1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93–0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90–0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90–0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92–0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93–0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. Conclusions: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.

Published
2020

9. Statin Use and Skin Cancer Risk: A Prospective Cohort Study

Author

Trude Eid Robsahm, Agnès Fournier, Yahya Mahamat-Saleh, Reza Ghiasvand, Marina Kvaskoff, Manon Cairat, Marie-Christine Boutron-Ruault, Iris Cervenka, Marie Al Rahmoun, Gianluca Severi, 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, Oslo University Hospital [Oslo], Cancer Registry of Norway, International Agency for Cancer Research (IACR), Università degli Studi di Firenze = University of Florence (UniFI), 2102 918823, NCT03285230, Centre International de Recherche sur le Cancer, CIRC, Agence Nationale de la Recherche, ANR: ANR-10-COHO-0006, Institut National de la Santé et de la Recherche Médicale, Inserm, Institut National Du Cancer, INCa: INCa_13539, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, We are grateful to the study participants for their continued participation and to practitioners for providing pathology reports. We also thank all members of the E3N study group, particularly Rafika Cha?t, Ghizlane Bajawi-Esselma, Amandine Gelot, Marie Fangon, Pascale Gerbouin-R?rolle, Sabine Moreira-Faria, Nad?ge Senina, Sofiane Harizi, Lyan Hoang, Anita Kowal, and Camille Laplanche for their technical assistance. The E3N cohort from the French National Institute of Health and Medical Research (Inserm) was supported by the Mutuelle G?n?rale de l'Education Nationale, the Gustave Roussy Institute, and the French League against Cancer. E3N-E4N is also supported by the French National Research Agency under the Investment for the Future Program (ANR-10-COHO-0006) and by the French Ministry of Higher Education, Research and Innovation (subsidy for public service charges #2102 918823). MAR, YMS, and IC were supported by research scholarships from the French National Cancer Institute (MAR: INCa_13539), the Paris Ile-de-France region, and the French Ministry of Research, respectively. This study is listed at ClinicalTrials.gov as NCT03285230. The work reported in this paper was performed during Agn?s Fournier's term as a Visiting Scientist at the International Agency for Research on Cancer. Conceptualization: MK, AF, Data Curation: MAR, AF, Formal Analysis: MAR, Funding Acquisition: MAR, MK, AF, Investigation: MAR, MK, AF, Methodology: MK, AF, Project Administration: MK, AF, Resources: GS, MCBR, MK, AF, Software: MAR, AF, Supervision: MK, AF, Visualization: MAR, Validation: MK, AF, Writing - Original Draft Preparation: MAR, RG, TER, MK, AF, Writing - Review and Editing: MAR, RG, MC, YMS, IC, GS, MCBR, TER, MK, AF, Funding sources had no role in study design, collection, analysis, and interpretation of data, writing of the report, and the decision to submit the article for publication., ANR-10-COHO-0006,E4N,Etude Epidémiologique des Enfants de femmes de l'Education Nationale(2010), HAL UVSQ, Équipe, and Cohortes - Etude Epidémiologique des Enfants de femmes de l'Education Nationale - - E4N2010 - ANR-10-COHO-0006 - COHO - VALID

Subjects
Male, medicine.medical_specialty, Skin Neoplasms, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Biochemistry, Cohort Studies, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, Epidemiology, medicine, Humans, Basal cell carcinoma, Prospective Studies, Prospective cohort study, Melanoma, Molecular Biology, Proportional Hazards Models, Aged, 80 and over, business.industry, Hazard ratio, Cell Biology, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, Confidence interval, [SDV] Life Sciences [q-bio], Defined daily dose, Carcinoma, Basal Cell, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Carcinoma, Squamous Cell, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Skin cancer, business, Body mass index, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

International audience; Epidemiological studies on statin use in relation to skin cancer risk are scarce and yielded conflicting results. We explored this association in Etude Epidémiologique auprès de femmes de l'Education Nationale, a prospective cohort of French women born in 1925–1950. Health and lifestyle data were self-reported biennially and matched with drug reimbursement data, allowing the identification of participants’ statin use since 2004. Multivariable cause-specific hazards regression models adjusted for skin cancer risk factors estimated hazard ratios with 95% confidence intervals. Over 2004–2014, 455 cutaneous melanoma, 1,741 basal cell carcinoma, and 268 squamous cell carcinoma cases were ascertained among 62,473 women. Compared with never use, there were no associations between ever use of statins and melanoma (hazard ratio = 1.16, 95% confidence interval = 0.94–1.44) or squamous cell carcinoma (hazard ratio = 0.89, 95% confidence interval = 0.66–1.19) risks and a decrease in basal cell carcinoma risk with ever use of statins (hazard ratio = 0.89, 95% confidence interval = 0.79–0.996). We found no trend of increasing or decreasing risks with dose, duration of use, time since first use, or age at first use and no statistically significant effect modification by pigmentary traits or residential UVR exposure. Because of the limited number of studies evaluating the associations between the use of statins and the risks of melanoma, basal cell carcinoma, and squamous cell carcinoma, these findings would deserve further investigation in other settings.

Published
2022

10. HAT cofactor TRRAP mediates β-Catenin ubiquitination on the chromatin and the regulation of the canonical Wnt pathway

Author

Rabih Murr, Maria Ouzounova, Zdenko Herceg, Carla Sawan, Martin G. Finkbeiner, and Centre international de Recherche sur le Cancer (CIRC)

Subjects
[SDV]Life Sciences [q-bio], Context (language use), Models, Biological, Cell Line, Chromatin/metabolism, 03 medical and health sciences, 0302 clinical medicine, Ubiquitin, Wnt Proteins/metabolism, Skp1, Humans, Histone Acetyltransferases/metabolism, RNA, Small Interfering, S-Phase Kinase-Associated Proteins, Molecular Biology, ComputingMilieux_MISCELLANEOUS, beta Catenin, Adaptor Proteins, Signal Transducing, Histone Acetyltransferases, Nuclear Proteins/metabolism, 030304 developmental biology, 0303 health sciences, biology, S-Phase Kinase-Associated Proteins/metabolism, Ubiquitination, Wnt signaling pathway, Nuclear Proteins, Cell Biology, Histone acetyltransferase, Molecular biology, Chromatin, Cell biology, Wnt Proteins, Adaptor Proteins, Signal Transducing/metabolism, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Catenin, Ubiquitin ligase complex, biology.protein, Beta Catenin/metabolism, Signal Transduction, Developmental Biology
Abstract

The Wnt pathway is a key regulator of embryonic development and stem cell self-renewal, and hyperactivation of the Wnt signalling is associated with many human cancers. The central player in the Wnt pathway is beta-catenin, a cytoplasmic protein whose function is tightly controlled by ubiquitination and degradation, however the precise regulation of beta-catenin stability/degradation remains elusive. Here, we report a new mechanism of beta-catenin ubiquitination acting in the context of chromatin. This mechanism is mediated by the histone acetyltransferase (HAT) complex component TRRAP and Skp1, an invariable component of the Skp-Cullin-F-box (SCF) ubiquitin ligase complex. TRRAP interacts with Skp1/SCF and mediates its recruitment to beta-catenin target promoter in chromatin. TRRAP deletion leads to a reduced level of beta-catenin ubiquitination, lower degradation rate and accumulation of beta-catenin protein. Furthermore, recruitment of Skp1 to chromatin and ubiquitination of chromatin-bound beta-catenin are abolished upon TRRAP knock-down, leading to an abnormal retention of beta-catenin at the chromatin and concomitant hyperactivation of the canonical Wnt pathway. These results demonstrate that there is a distinct regulatory mechanism for beta-catenin ubiquitination/ destruction acting in the nucleus which functionally complements cytoplasmic destruction of beta-catenin and prevents its oncogenic stabilization and chronic activation of the canonical Wnt pathway.

Published
2008

11. SCREENING MULTIPLE ENDOCRINE NEOPLASIA TYPE 2A FAMILIES USING DNA MARKERS

Author

Colette Bonnardel, Hagay Sobol, Anne Salvetti, G. M. Lenoir, and Centre international de Recherche sur le Cancer (CIRC)

Subjects
Genetic Markers, Genetics, 0303 health sciences, business.industry, Multiple Endocrine Neoplasia, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Biology, 03 medical and health sciences, 0302 clinical medicine, Text mining, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic marker, 030220 oncology & carcinogenesis, Multiple Endocrine Neoplasia Type 2a, Humans, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience

Published
1988

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