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51. Genetic engineering of lactic acid bacteria to produce optically pure lactic acid and to develop a novel cell immobilization method suitable for industrial fermentations

Author: Kylä-Nikkilä, Kari, University of Helsinki, Faculty of Agriculture and Forestry, Department of Food and Environmental Sciences, Division of Microbiology and Biotechnology, Division of Microbiology and Epidemiology, Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsingin yliopisto, maatalous-metsätieteellinen tiedekunta, elintarvike- ja ympäristötieteiden laitos, Helsingfors universitet, agrikultur-forstvetenskapliga fakulteten, institutionen för livsmedels- och miljövetenskaper, Nyyssölä, Antti, Saris, Per, and Palva, Airi
Subjects: mikrobiologia ja biotekniikka
Abstract: Mankind has exploited lactic acid bacteria for thousands of years. For most of this time, the use of these bacteria was based on tradition without deeper knowledge of the nature of these organisms. Nowadays, we have learned to know lactic acid bacteria and we are capable to genetically modify these organisms. In this thesis, methods to modify Lactobacillus helveticus bacterium to produce optically pure L(+)-lactic acid are introduced. Also, a method to immobilize lactic acid bacteria on unmodified cellulosic material is described. Lactic acid has two optical isomers: D(-)-lactic acid and L(+)-lactic acid. Most typically lactic acid is produced by microbial fermentation process. When using strains belonging to genus Lactobacillus in these fermentations, the produced lactic acid is most typically mixture of D(-)- and L(+)-lactic acid. In certain industrial applications, like that of the production of biodegradable plastic, pure L(+)-lactic acid is the preferred choice to be used as a raw material. In this work, two novel Lactobacillus helveticus strains were constructed for this purpose. As demonstrated by experiments, both these strains are potential producers of plastic grade L(+)-lactic acid. In many industrial-scale fermentation processes, it is beneficial to immobilize production strain on a solid carrier, whenever possible. From economical point of view, this kind of approach is very attractive especially if the immobilization is possible to carry out with minimal use of chemicals and processing steps. In this work Lactococcus lactis was genetically engineered to provide binding to chemically unmodified cellulosic carrier material. Putatively, by applying this method in an industrial-scale setup, it is possible to develop novel continuous fermentation processes. Ihmiskunta on käyttänyt hyödykseen maitohappobakteereita jo tuhansia vuosia. Hyvin pitkään maitohappobakteerien käyttö perustui sukupolvelta toiselle siirtyneeseen kokemusperäiseen tietoon - ilman näiden organismien varsinaista tuntemista. Nykyään olemme oppineet tuntemaan maitohappobakteerit ja oppineet myös geneettisesti muokkaamaan niiden ominaisuuksia. Tässä väitöskirjassa esitellään keinoja puhtaan L(+)-maitohapon tuottamiseksi Lactobacillus helveticus-bakteerin avulla sekä menetelmä jolla maitohappobakteerit voidaan muokata siten, että ne pystyvät kiinnittymään selluloosapohjaiseen kantajamateriaaliin. Maitohappomolekyylillä on kaksi optisesti aktiivista muotoa: D(-)-maitohappo ja L(+)-maitohappo. Maitohappo tuotetaan teollisesti useimmiten mikrobiologisesti ja tyypillisesti Lactobacillus-suvun tuottajakannoilla lopputuotteena syntyy D(-)- ja L(+) maitohapon seos. Tietyissä teollisissa käyttökohteissa, kuten biohajoavien muovien valmistuksessa, raaka-aineeksi halutaan usein mahdollisimman puhdasta L(+)-maitohappoa. Tässä työssä muokattiin kaksi uutta Lactobacillus helveticus-kantaa, joiden tuottaman L(+)-maitohapon puhtaus soveltuu hyvin biohajoavien muovien valmistukseen. Teollisen mittakaavan fermentaatio-prosesseissa on usein etuna jos tuottajakanta voidaan sitoa kiinni kantaja-materiaaliin. Prosessin kustannustehokkuuden kannalta erityisen mielenkiintoisia ovat sovellukset joissa tämä sitominen vaatii mahdollisimman vähän ylimääräisiä kemikaaleja ja käsittelyitä. Tässä työssä muokattiin Lactococcus lactis-kantaa siten, että se pystyi sitoutumaan kemiallisesti käsittelemättömän selluloosamateriaalin pintaan. Soveltamalla tässä työssä kehiteltyä menetelmää, on mahdollista luoda jatkuvatoimisia teollisia prosesseja joissa tuottajaorganismi on sidottu kantaja-aineeseen.
Published: 2016

52. The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort

Author: María José Sánchez, Jennifer Ose, Antonia Trichopoulou, J. Ramón Quirós, Marc J. Gunter, Xavier Castellsagué, Carlotta Sacerdote, Inger T. Gram, H B As Bueno-de-Mesquita, Johanna Ekström, Ruth C. Travis, Joakim Dillner, Carmen Navarro, Silvia de Sanjosé, Annika Idahl, Renée T. Fortner, Domenico Palli, Noémie Travier, Amalia Mattiello, David Lindquist, Annika Steffen, Elisabete Weiderpass, Christian Munk, Kay-Tee Khaw, Aurelio Barricarte, Elio Riboli, Michael Pawlita, Petra H.M. Peeters, Valeria Pala, Eiliv Lund, Philippos Orfanos, Sabina Rinaldi, F. Xavier Bosch, Pagona Lagiou, Kim Overvad, Nerea Larrañaga, N. Margall, Sylvie Mesrine, Massimo Tommasino, Silvia Franceschi, Silvia Polidoro, Melissa A. Merritt, Tim Waterboer, Giovanna Masala, Agnès Fournier, Rosario Tumino, Esther Roura, Anne Tjønneland, Françoise Clavel-Chapelon, University Medical Center Utrecht, Imperial College Trust, [Roura,E, de Sanjosé,S, Bosch,FX, Castellsagué,X] Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Roura,E, Sánchez,MJ, Navarro,C, Barricarte,A, Larrañaga,N, Castellsagué,X] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Travier,N] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Waterboer,T, Pawlita,M] Division of Molecular Diagnostics of Oncogenic Infections (F020), Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.[Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Weiderpass, Dillner,J] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Weiderpass,E, Gram,IT, Lund,E] Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. [Margall,N] Microbiology Department, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain. [Dillner,J] Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. [Tjønneland,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Munk,C] Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. [Palli,D, Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute–ISPO, Florence, Italy. [Khaw,K] School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Mesrine,S, Fournier,A] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. Université Paris Sud, Villejuif, France.Institut Gustave Roussy, Villejuif, France. [Fortne,RT, Ose,J] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Steffen,A] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Lagiou,P, Orfanos,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Boston, United States of America. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic—M.P. Arezzo' Hospital, Ragusa, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, University of Turin, Turin, Italy. Centre for Cancer Epidemiology and Prevention (CPO Piemonte), Turin, Italy. [Polidoro,S] Human Genetics Foundation (HuGeF), Turin, Italy. [Mattiello,A] Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy. [Peeters,PH] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] 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.[Bueno-de-Mesquita,HB, Merritt,MA, Gunter,MJ, Riboli,E] Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. [Bueno-de-Mesquita,HB] Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.[Quirós,JR] Public Health Directorate, Asturias, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Barricarte,A] Navarra Public Health Institute, Pamplona, Spain. Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Larrañaga,N] Public Health Division of Gipuzkoa, BIODonostia Research Institute, Basque Health Department, Bilbao, Spain. [Ekström,J] BBMRI.se Service Center for Southern Sweden, Lund University, Medicon Village, Lund, Sweden. [Lindquist,D] Department of Radiation Sciences, Umeå University, Umeå, Sweden. [Idahl,A] Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. [Rinaldi,S, Tommasino,M, Franceschi,S] International Agency for Research on Cancer, Lyon, France., Funding: The work was partially supported by grants from the Instituto de Salud Carlos III (Spanish Government) (grants FIS PI08/1308, PI13/00053, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RD12/0036/0056, RD12/0036/0018, and CIBERESP) and from the Agència de Gestió d’Ajuts Universitaris i de Recerca – Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2005SGR00695, 2009SGR939 and 2009SGR126, 2014SGR1077, 2014SGR2016). 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 the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and the Catalan Institute of Oncology, La Caixa (BM 06-130), RTICC-RD06/10091 (Spain), 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), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC) 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) and Statistics Netherlands (The Netherlands), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council (United Kingdom), and Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway).
Subjects: Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in Situ::Cervical Intraepithelial Neoplasia [Medical Subject Headings], Oncology, Replacement therapy, Pathology and Laboratory Medicine, Antibodies, Viral, Biochemistry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pregnancy, Prospective Studies, lcsh:Science, Gonadal Steroid Hormones, education.field_of_study, Hormonal Therapy, Contraceptives, Humanos, Anticonceptivos, 030220 oncology & carcinogenesis, Cohort, Carcinoma, Squamous Cell, Cohort studies, Science & Technology - Other Topics, Intreaepithelial neoplasia, Human, Cohort study, Oral, Human Papillomavirus Infection, medicine.medical_specialty, Càncer de coll uterí, Sexually Transmitted Diseases, Estudios retrospectivos, 03 medical and health sciences, Drug Therapy, Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Uterine Cervical Neoplasms [Medical Subject Headings], Neoplasias del cuello uterino, Humans, education, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Parity [Medical Subject Headings], Aged, Pharmacology, Gynecology, Cancer och onkologi, Science & Technology, Herpes Genitalis, Genitourinary Infections, Herpesvirus 2, lcsh:R, Case-control study, Biology and Life Sciences, Estrogens, medicine.disease, Hormones, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, Case-Control Studies, Cervical cancer, Medical Devices and Equipment, lcsh:Q, Intrauterine Devices, 0301 basic medicine, Glutathione-S-transferase, Viral Diseases, Human papillomavirus infection, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Herpesvirus 2, Human, lcsh:Medicine, Uterine Cervical Neoplasms, Chlamydia trachomatis, Cervical Cancer, Cohort Studies, Cervix cancer, Paridad, Medicine and Health Sciences, Viral, Non-U.S. Gov't, Prospective cohort study, Papillomaviridae, Reproductive History, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Reproductive Control Agents::Contraceptive Agents [Medical Subject Headings], Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings], Multidisciplinary, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Pharmaceutics, Research Support, Non-U.S. Gov't, Femenino, Drugs, Estudios de Casos y Controles, Middle Aged, humanities, Multidisciplinary Sciences, Infectious Diseases, Serology, Research Design, Hormonal therapy, Female, Research Article, Biotechnology, Adult, Risk, Papillomaviruses, Embarazo, General Science & Technology, Hormone Replacement Therapy, Urology, Population, Individual data, Research Support, Research and Analysis Methods, Cervical intraepithelial neoplasia, Antibodies, Contraceptives, Oral, Hormonal, Young Adult, Collaborative reanalysis, Internal medicine, Oral-contraceptives, MD Multidisciplinary, Journal Article, medicine, Multicentric case-control, Cervical Intraepithelial Neoplasia, Neoplasia Intraepitelial Cervical, Papil·lomavirus, Reproductive factors, Hormonal, business.industry, Carcinoma, Papillomavirus Infections, Cancers and Neoplasms, Chlamydia Infections, Uterine Cervical Dysplasia, Squamous Cell, Organisms::Viruses::DNA Viruses::Papillomaviridae [Medical Subject Headings], business, Gynecological Tumors, Follow-Up Studies
Abstract: 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 the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130) In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
Published: 2016

53. 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

54. The Contribution of Risk Factors to the Higher Incidence of Invasive and In Situ Breast Cancers in Women With Higher Levels of Education in the European Prospective Investigation Into Cancer and Nutrition

Author: Elio Riboli, Carla H. van Gils, Gillian K Reeves, Tonje Braaten, María José Sánchez, Kim Overvad, Naomi E. Allen, Amelia Mattiello, Eric J. Duell, Anton E. Kunst, Petra H.M. Peeters, Kay-Tee Khaw, Anne-Kathrin Illner, Domenico Palli, Pagona Lagiou, Valentina Gallo, Anja Olsen, Eiliv Lund, Eva Ardanaz, José Ramón Quirós, Signe Borgquist, Manuela M. Bergmann, Paolo Vineis, Franco Berrino, Jonas Manjer, Carmen Navarro, Veronique Chajes, Rudolf Kaaks, Sabina Rinaldi, Carlotta Sacerdote, Silke Hermann, Rosario Tumino, A. M. May, Antonia Trichopoulou, Dimitrios Trichopoulos, Evelyn M. Monninkhof, Anne Tjønneland, Gwenn Menvielle, Hendriek Boshuizen, H. Bas Bueno-de-Mesquita, Nadia Slimani, Amsterdam Public Health, Public and occupational health, Department of Public Health, Erasmus University Medical Center [Rotterdam] (Erasmus MC), 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), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Amsterdam [Amsterdam] (UvA), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Dept of Epidemiology and Public Health, Imperial College London, Department of Cardiology and Department of Clinical Epidemiology, Aarhus University Hospital, Cancer Epidemiology Institute, Danish Cancer Society, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Dept of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Epidemiology, Havard School of Public Health, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Department of Preventive & Predictive Medicine, Fondazione IRCCS-Istituto Nazionale dei Tumori, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, CPO Piemonte, Institute of Community Medicine, University of Tromsø (UiT), Public Health and Health Planning Directorate, Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Andalusian School of Public Health [Granada], CIBERESP, CIBER Epidemiologia y Salud Pública, Epidemiology Department, Murcia Health Council, Public Health Institute of Navarra, Department of Oncology, Lund University Hospital-Lund University [Lund], Department of surgery, Lund University [Lund]-Malmö University Hospital, Dept of Public Health and Primary Care, University of Cambridge [UK] (CAM)-MRC Center for Nutritional Epidemiology and Cancer Prevention and Survival, Cancer Epidemiology Unit, University of Oxford [Oxford]-Cancer Epidemiology Unit, International Agency for Cancer Research (IACR), University of Torino and CPO-Piemonte, Università degli studi di Torino (UNITO), ISI Foundation Institute for Scientific Interchange, G Menvielle received a funding from the Fondation pour la Recherche Médicale for this analysis. The project was in part funded by the European Commission, through the Eurocadet project (from the commission of the European communities research directorate-general, grant No EUROCADET:SP23-CT-2005-006528). EPIC was supported by the European Commission: Public Health and Consumer Protection Directorate 1993-2004 and the Research Directorate-General 2005-2008. European Commission FP5 project (QLG1-CT-2001-01049). The EPIC study was funded by 'Europe Against Cancer' Programme of the European Commission (SANCO), Ligue contre le Cancer (France), Société 3M (France), Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale, German Cancer Aid, German Cancer Research Center, German Federal Ministry of Education and Research, Red Temática de Investigación Cooperativa de Centros de Cáncer (C03/10), the participating regional governments and institutions of Murcia, Navarra, Asturias, Pais Vasco y Andalucia, Spain, Cancer Research UK, Medical Research Council, United Kingdom, Stroke Association, United Kingdom, British Heart Foundation, Department of Health, United Kingdom, Food Standards Agency, United Kingdom, The Wellcome Trust, United Kingdom, Greek Ministry of Health, Stavros Niarchos Foundation, Italian Association for Research on Cancer, Dutch Ministry of Public Health, Welfare and Sports, Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, Dutch Zorg Onderzoek Nederland, World Cancer Research Fund, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Vasterbotten and Skane, Sweden, Norwegian Cancer Society, and Foundation to Promote Research into Functional Vitamin B12 Deficiency, Norway. Some authors are partners of Environmental Cancer Risk, Nutrition and Individual Susceptibility, a network of excellence of the European Commission (6FP contract 513943). Antonio Agudo and Paolo Vineis were supported by ECNIS., Schmaus, Annie, 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), University of Naples Federico II = Università degli studi di Napoli Federico II, Lund University [Lund]-Lund University Hospital, University of Oxford-Cancer Epidemiology Unit, Università degli studi di Torino = University of Turin (UNITO), Public Health, and Cell biology
Subjects: MESH: Reproductive History, Epidemiology, MESH: Risk Assessment, 0302 clinical medicine, MESH: Risk Factors, Prevalence, breast neoplasms, Mass Screening, risk factors, Prospective Studies, 030212 general & internal medicine, MESH: Incidence, Prospective cohort study, reproductive history, MESH: Aged, education, MESH: Middle Aged, Obstetrics, Incidence (epidemiology), MESH: Follow-Up Studies, Middle Aged, Nutrition Surveys, Prognosis, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, 030220 oncology & carcinogenesis, Educational Status, Female, Breast disease, Risk assessment, Adult, medicine.medical_specialty, Risk Assessment, Article, MESH: Prognosis, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, MESH: Nutrition Surveys, medicine, Humans, Neoplasm Invasiveness, MESH: Mass Screening, Risk factor, MESH: Prevalence, Aged, Gynecology, MESH: Humans, business.industry, Cancer, MESH: Adult, MESH: Neoplasm Invasiveness, medicine.disease, MESH: Prospective Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, incidence, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Europe, business, MESH: Educational Status, MESH: Female, MESH: Breast Neoplasms, Follow-Up Studies
Abstract: International audience; The authors investigated the role of known risk factors in educational differences in breast cancer incidence. Analyses were based on the European Prospective Investigation Into Cancer and Nutrition and included 242,095 women, 433 cases of in situ breast cancer, and 4,469 cases of invasive breast cancer. Reproductive history (age at first full-term pregnancy and parity), exposure to endogenous and exogenous hormones, height, and health behaviors were accounted for in the analyses. Relative indices of inequality (RII) for education were estimated using Cox regression models. A higher risk of invasive breast cancer was found among women with higher levels of education (RII = 1.22, 95% confidence interval (CI): 1.09, 1.37). This association was not observed among nulliparous women (RII = 1.13, 95% CI: 0.84, 1.52). Inequalities in breast cancer incidence decreased substantially after adjusting for reproductive history (RII = 1.11, 95% CI: 0.98, 1.25), with most of the association being explained by age at first full-term pregnancy. Each other risk factor explained a small additional part of the inequalities in breast cancer incidence. Height accounted for most of the remaining differences in incidence. After adjusting for all known risk factors, the authors found no association between education level and risk of invasive breast cancer. Inequalities in incidence were more pronounced for in situ breast cancer, and those inequalities remained after adjustment for all known risk factors (RII = 1.61, 95% CI: 1.07, 2.41), especially among nulliparous women.
Published: 2011
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55. Prediction, Assessment of the Rift Valley Fever Activity in East and Southern Africa 2006–2008 and Possible Vector Control Strategies

Author: Patrick Nguku, Allen W. Hightower, Robert Swanepoel, Seth C. Britch, Jennifer Small, David Schnabel, Mohamed A. Mohamed, Mark D. Latham, Robert F. Breiman, Stephane de La Rocque, Salih Osman Magdi, Jean-Paul Chretien, Pierre Formenty, Jean-Marc Reynes, Edwin W. Pak, Henry B. Lewandowski, Compton J. Tucker, Kenneth J. Linthicum, Assaf Anyamba, Rosemary Sang, Karl A. Haagsma, NASA Goddard Space Flight Center (GSFC), USDA-ARS Center for Medical, Agricultural and Veterinary Entomology, USDA-ARS : Agricultural Research Service, EMPRES/Animal Production and Health Division (AGAH), Food and Agriculture Organization of the United Nations, Global Alert and Response Department (HSE/GAR), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Kenya Medical Research Unit (KEMRI-CDC), Kenya Medical Research Institute (KEMRI), Division of Preventive Medicine, Walter Reed Army Institute of Research, United States Army Medical Research Unit-Kenya, United States Army Medical Research Directorate [Kenya] (USAMRD-K), 757th Airlift Squadron, Youngstown Air Reserve Station, Manatee County Mosquito Control, Chatham County Mosquito Control, Federal Ministry of Health, Epidemiology Department, Ministry of Health and Social Welfare, Division of Communicable Disease Control, Ministry of Health [Mozambique], Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), National Institute for Communicable Diseases [Johannesburg] (NICD), Kenya Medical Research Unit, and National Institute for Communicable Diseases (NICD)
Subjects: Rift Valley Fever, Climate, Rain, MESH: Satellite Communications, MESH: Risk Assessment, Disease Outbreaks, 0302 clinical medicine, Aedes, MESH: Rift Valley Fever, MESH: Animals, MESH: Disease Outbreaks, Rift Valley fever, 0303 health sciences, Temperature, Articles, MESH: Aedes, Vegetation, Africa, Eastern, Satellite Communications, MESH: Climate, MESH: Temperature, Culex, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Geography, Habitat, Animals, Domestic, Livestock, MESH: Forecasting, 030231 tropical medicine, MESH: Culex, MESH: Insect Vectors, Risk Assessment, Africa, Southern, 03 medical and health sciences, Virology, parasitic diseases, medicine, Animals, Humans, MESH: Animals, Domestic, Epizootic, 030304 developmental biology, MESH: Africa, Eastern, MESH: Humans, business.industry, Outbreak, medicine.disease, Insect Vectors, El Niño, 13. Climate action, Vector (epidemiology), MESH: Rain, Parasitology, MESH: Africa, Southern, Physical geography, business, Forecasting
Abstract: International audience; Historical outbreaks of Rift Valley fever (RVF) since the early 1950s have been associated with cyclical patterns of the El Niño/Southern Oscillation (ENSO) phenomenon, which results in elevated and widespread rainfall over the RVF endemic areas of Africa. Using satellite measurements of global and regional elevated sea surface temperatures, elevated rainfall, and satellite derived-normalized difference vegetation index data, we predicted with lead times of 2-4 months areas where outbreaks of RVF in humans and animals were expected and occurred in the Horn of Africa, Sudan, and Southern Africa at different time periods from September 2006 to March 2008. Predictions were confirmed by entomological field investigations of virus activity and by reported cases of RVF in human and livestock populations. This represents the first series of prospective predictions of RVF outbreaks and provides a baseline for improved early warning, control, response planning, and mitigation into the future.
Published: 2010

56. Impact of misclassification error on prevalence estimates of epilepsy and severe chronic headaches in Burkina Faso

Author: Sahlu, Ida, Carabin, Hélène, Ganaba, Rasmané, Preux, Pierre-Marie, Millogo, Athanase, Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), CHU Limoges, Laboratoire de Biostatistique et d'Informatique Médicale, Université de Limoges (UNILIM), Epidemiology Department Program, and Grelier, Elisabeth
Subjects: [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2015

57. 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

58. Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients

Author: Paige M. Bracci, Celine M. Vachon, Thomas Martin, Shaji Kumar, Daniel J. Serie, Alexandra J. Greenberg, Laura Fejerman, Djordje Atanackovic, Brandt Jones, Federico Canzian, Robert B. Diasio, Vincent Rajkumar, Jeffrey L. Wolf, Blake T. Aftab, Alessandro Martino, Susan L. Slager, Herlander Marques, Donglei Hu, Eric Dean, Marek Dudziński, Martha Glenn, Yi Zhao, Marzena Wątek, Nicola J. Camp, Elad Ziv, Karen Curtin, Adam M. Lee, Juan Sainz, Joaquin Martinez-Lopez, Artur Jurczyszyn, Lisa A. Cannon-Albright, Charles Dumontet, Scott Huntsman, Jennifer L. Caswell-Jin, Annette Juul Vangsted, Daniele Campa, Gabriele Buda, Krzysztof Jamroziak, [Ziv,E, Hu,D, Caswell.Jin,J,H, Fejerman,L, Huntsman,S] Division of General Internal Medicine, Department of Medicine, Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California USA. [Dean,E] Sutter Medical Center of Santa Rosa, Santa Rosa, California USA. [Martino,A, Campa,D, Canzian,F] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Serie,D] Division of Biomedical Statistics and Informatics. Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida USA. [Curtin,K, Zhao,Y, Atanackovic,D, Glenn,M, Cannon-Albright,L, Jones,B, Camp,NJ] Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, USA. [Aftalb,B, Martin,T, Wolf,J]Division of Hematology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California USA. [Bracci,P] Department of Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California , USA. [Buda,G] Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University Hospital, Pisa, Italy. [Diasio,R, Lee,A] Department of Molecular Pharmacology and Experimental Therapeutics, College of Medicine, Mayo Clinic, Rochester, Minnesota USA. [Dumontet,C] INSERM UMR 1052/CNRS 5286, Laboratoire de Cytologie Analytique, Faculte´ de Me´decine Rockefeller, Universite´ Claude Bernard Lyon I, Lyon, France. [Dudzinski,M] Department of Hematology, Rzeszow Regional Hospital, Rzeszow 35-301, Poland. [Greenberg,A] Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905, USA. [Greenberg,A, Vachon, C] Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. [Jamroziak,K] Department of Hematology, Medical University of Lodz, Lodz, Poland. [Jurczyszyn,A] Department of Hematology, Cracow University Hospital, Cracow, Poland. [Kumar,S, Rajkumar,V] Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA. [Marques,H] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga , Portugal. [Martinez-Lopez,J] Hematology Service, CRIS facility for Hematological research, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain. [Sainz,J] Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain. Department of Hematology, Virgen de las Nieves University Hospital, Granada, Spain. [Vangsted,AJ] Department of Hematology, Righospitalet and Roskilde Hospital, Copenhagen University, Copenhagen, Denmark. [Watek,M] Department of Hematology, Holycross Cancer Center, Kielce, Poland. [Slager,S] Division of Biomedical Statistics and Informatics. Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota USA., and This work was supported by the Steve and Nancy Grand Multiple Myeloma Translational Initiative and a grant from Expression Analysis and a grant from the National Cancer Institute (R21CA191896). E.Z. is supported in part by a mid-career award in patient research from the National Cancer Institute (K24169004). Collection of blood samples from Polish patients and controls from Łodz area, and DNA extraction was supported by a grant from Polish Ministry of Science and Higher Education (No. NN402178334). DNA extraction from Danish healthy controls was supported by The Research Fund at Region Sjælland, Denmark. The Utah study was supported by LLS 6067–09, CA152336 and CA134674, with data collection made possible, in part, by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all data sets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI Cancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the NCI SEER Program with additional support from the Utah State Department of Health and the University of Utah.
Subjects: Oncology, medicine.medical_specialty, tumor, Ciências da Saúde [Ciências Médicas], General Physics and Astronomy, Genome-wide association study, Single-nucleotide polymorphism, Kaplan-Meier Estimate, Biology, Bioinformatics, Polymorphism, Single Nucleotide, survival, Article, General Biochemistry, Genetics and Molecular Biology, gene expression, genome, health risk, meta-analysis, polymorphism, social theory, Internal medicine, medicine, Humans, Allele, Gene, Multiple myeloma, Science & Technology, Multidisciplinary, General Chemistry, medicine.disease, Minor allele frequency, Meta-analysis, Cohort, Multiple Myeloma, Chromosomes, Human, Pair 16, Genome-Wide Association Study
Abstract: A corrigendum to this article was published on 09 December 2015: https://doi.org/10.1038/ncomms10203. The corrigendum is also available at: http://hdl.handle.net/1822/62281 This work was supported by the Steve and Nancy Grand Multiple Myeloma Translational Initiative and a grant from Expression Analysis and a grant from the National Cancer Institute (R21CA191896). E.Z. is supported in part by a mid-career award in patient research from the National Cancer Institute (K24169004). Collection of blood samples from Polish patients and controls from Łodz area, and DNA extraction was supported by a grant from Polish Ministry of Science and Higher Education (No. NN402178334).DNA extraction from Danish healthy controls was supported by The Research Fund at Region Sjælland, Denmark. The Utah study was supported by LLS 6067–09, CA152336and CA134674, with data collection made possible, in part, by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all data sets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCICancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the NCI SEER Program with additional support from the Utah State Department of Health and the University of Utah. In Utah, we thank Jathine Wong for support in formatting files and advice on R programming. Several authors (E.Z., N.C., F.C., C.V.) are members of the International Multiple Myeloma Consortium. We are grateful to the leadership and other members of the International Multiple Myeloma Consortium for facilitating this collaborative study.
Published: 2015

59. Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study

Author: Carla H. van Gils, E. Riboli, Christos Tsironis, Anne-Claire Vergnaud, H. Bas Bueno-de-Mesquita, Laureen Dartois, José Ramón Quirós, Veronika Fedirko, Pietro Ferrari, Teresa Norat, Pagona Lagiou, Christina C. Dahm, Giovanna Masala, Timothy J. Key, Mark J. Gunter, Maria Wennberg, Kay-Tee Khaw, Verena Katzke, Petra H.M. Peeters, Aurelio Barricarte, Heather Ward, Nicholas J. Wareham, Anne Tjønneland, Lena Maria Nilsson, Bodil Ohlsson, Valeria Pala, Laure Dossus, Antonia Trichopoulou, Tilman Kühn, Heiner Boeing, Elisabete Weiderpass, Petra A. Wark, M. Dorronsoro, Carmen Navarro, Camilla Plambeck Hansen, Genevieve Buckland, Salvatore Panico, Marie-Christine Boutron-Ruault, María José Sánchez, Paolo Vineis, Peter D. Siersema, Karin Jirström, Dora Romaguera, Rosario Tumino, Mazda Jenab, Romaguera, Dora, Ward, Heather, Wark, Petra A, Vergnaud, Anne Claire, Peeters, Petra H, van Gils, Carla H, Ferrari, Pietro, Fedirko, Veronika, Jenab, Mazda, Boutron Ruault, Marie Christine, Dossus, Laure, Dartois, Laureen, Hansen, Camilla Plambeck, Dahm, Christina Catherine, Buckland, Genevieve, Sánchez, María José, Dorronsoro, Miren, Navarro, Carmen, Barricarte, Aurelio, Key, Timothy J, Trichopoulou, Antonia, Tsironis, Christo, Lagiou, Pagona, Masala, Giovanna, Pala, Valeria, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Siersema, Peter D, Ohlsson, Bodil, Jirström, Karin, Wennberg, Maria, Nilsson, Lena M, Weiderpass, Elisabete, Kühn, Tilman, Katzke, Verena, Khaw, Kay Tee, Wareham, Nick J, Tjønneland, Anne, Boeing, Heiner, Quirós, José R, Gunter, Marc J, Riboli, Elio, Norat, Teresa, Department of Medical and Clinical Genetics, Medicum, BMC, BMC, Department of Epidemiology and Public Health, Imperial College London, Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, CIBER Fisiopatología de la Obesidad y Nutrición ( (CIBEROBN)), Instituto de Salud Carlos III [Madrid] (ISC), Department of Primary Care and Public Health, Department of Epidemiology, University Medical Center [Utrecht]-Julius Center for Health Sciences and Primary Care, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Emory University [Atlanta, GA]-Rollins School of Public Health-Winship Cancer Institute, 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), Section for Epidemiology, Aarhus University [Aarhus], Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL)-Cancer Epidemiology Research Programme, Granada Cancer Registry, Andalusian School of Public Health [Granada], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Murcia Regional Health Council [Murcia], Department of Health and Social Sciences, Universidad de Murcia, Navarre Public Health Institute, Cancer Epidemiology Unit, University of Oxford, Hellenic Health Foundation, Bureau of Epidemiologic Research, Academy of Athens, Department of Hygiene, Epidemiology and Medical Statistics, Harvard School of Public Health, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Cancer Registry and Histopathology Unit, Department of Oncology-Civile - M.P.Arezzo Hospital, Human Genetics Foundation (HuGeF), Università degli studi di Torino = University of Turin (UNITO), Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II = Università degli studi di Napoli Federico II, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Center [Utrecht], Division of Internal Medicine, Skane University Hospital [Malmo], Lund University [Lund]-Lund University [Lund], Division of Oncology and Pathology, Lund University [Lund], Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Arctic Research Centre, Department of Community Medicine, The Arctic University of Norway [Tromsø, Norway] (UiT), Department of Research, Cancer Registry of Norway, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Clinical Gerontology Unit, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Danish Cancer Society Research Center, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Public Health Directorate, Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, 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), University of Oxford [Oxford], Università degli studi di Torino (UNITO), University of Naples Federico II, University of Malaya, The Arctic University of Norway, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, [Romaguera,D, Ward,H, Vergnaud,A, Peeters,PH, Vineis,P, Bueno-de-Mesquita,HB, Gunter, MJ, Riboli,E, Norat,T] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Romaguera,D] Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. [Romaguera,D] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Wark,PA] Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK. [Peeters,PH, Gils, CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Ferrari,P, Jenab,M] International Agency for Cancer Research (IARC), Lyon CEDEX, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, USA. [Fedirko,V] Winship Cancer Institute, Emory University, Atlanta, USA. [Boutron-Ruault,M, Dossus,L, Dartois,L] Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health (CESP), Vaillant, Villejuif, Cedex, France. [Boutron-Ruault,M, Dartois,L] Univ Paris Sud, Villejuif, France. [Boutron-Ruault,M, Dartois,L] Gustave Roussy, Villejuif, France. [Hansen,CP, Dahm,CC] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Dorronsoro,M, Navarro,C, Barricarte,A] CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Basque Regional Health Department, San Sebastian, Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Campus Universitario de Espinardo, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford UK. [Trichopoulou,A, Tsironis,C] Hellenic Health Foundation, Athens, Greece . [Trichopoulou,A, Lagiou,P] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic – M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P] HuGeF Foundation, Turin, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven The Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Ohlsson,B] Division of Internal Medicine, Department of Clinical Sciences, Skane University Hospital, Malmo, Lund University, Lund, Sweden. [Jirström,K] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Wennberg,M] Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. [Nilsson,LM] Arctic Research Centre, Umeå University, Umeå, Sweden. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, ISM - Universitetet i Tromsø, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Majorstuen Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Folkhälsan Research Center, Biomedicum 1, University of Helsinki, Helsinki, Finland. [Kühn,T, Katzke,V] German Cancer Research Center (DKFZ), Division of Cancer Epidemiology Im Neuenheimer Feld 581, Heidelberg, Germany. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit Box 251, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK. [Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Quirós,JR] Public Health Directorate, Oviedo Asturias, Spain., This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economía y Competitividad, Spain and European Regional Development Fund, RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO), German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), Danish Cancer Society, Catalan Institute of Oncology, Spain, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain, Cancer Research UK, Medical Research Council, United Kingdom, The Hellenic Health Foundation, Greece, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Fondazione-Istituto Banco Napoli, Italy, Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skåne, Sweden, Helga—Nordic Center of Excellence Programme in Nutrition and Health, French League against Cancer (LNCC), National Institute for Health and Medical Research (INSERM), France, Mutuelle Générale de l'Education Romaguera et al. BMC Medicine (2015) 13:107 Page 10 of 12 Nationale (MGEN), France, 3 M Co., France, Gustave Roussy Institute (IGR), France, and and General Councils of France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Subjects: Male, physical activity, 0302 clinical medicine, estudios prospectivos, Prospective Studies, estudios de cohortes, mediana edad, Aged, 80 and over, anciano, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activity [Medical Subject Headings], dieta, Incidence, Hazard ratio, COLON-CANCER, General Medicine, adulto, 3. Good health, Näringslära, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, estilo de vida, Cohort, Dieta, Estilo de Vida, RESEARCH FUND/AMERICAN INSTITUTE, Cohort study, Human, medicine.medical_specialty, Concordance, European Continental Ancestry Group, DIAGNOSIS, incidencia, White People, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Neoplasias Colorrectales, BREAST-CANCER, Humans, Life Style, Aged, Cancer prevention, Proportional hazards model, Physical activity, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], weight, LIFE-STYLE FACTORS, Colorectal cancer, REPRODUCTIVE HISTORY, Prospective Studie, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Proportional Hazards Model, grupo de ascendencia continental europea, Estudios de Cohortes, Gerontology, cumplimiento del paciente, Survival, modelos de riesgos proporcionales, VDP::Medisinske Fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803, [SDV]Life Sciences [q-bio], humanos, Colorectal Neoplasm, Alcohol consumption, Breast cancer, Prospective study, Named Groups::Persons::Survivors [Medical Subject Headings], Cohort Studies, 030212 general & internal medicine, Prospective cohort study, Non-U.S. Gov't, 2. Zero hunger, Medicine(all), RISK, Nutrition and Dietetics, Healthy lifestyle, Diet, Weight, Research Support, Non-U.S. Gov't, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, European Prospective Investigation into Cancer and Nutrition, VDP::Medical disciplines: 700::Health sciences: 800::Epidemiology medical and dental statistics: 803, NUTRITION, Female, Colorectal Neoplasms, Research Article, Adult, neoplasias colorrectales, 3122 Cancers, RECREATIONAL PHYSICAL-ACTIVITY, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], colorectal cancer, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research Support, survival, Sobrevivientes, healthy lifestyle, Internal medicine, medicine, Journal Article, Proportional Hazards Models, Actividad Motora, business.industry, Physical fitness, BODY-MASS INDEX, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Other Clinical Medicine, 3121 General medicine, internal medicine and other clinical medicine, Patient Compliance, Cohort Studie, business, diet, Condició física
Abstract: Background: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. Methods: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Results: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend, We would like to acknowledge the contribution of all participants in the study. This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economia y Competitividad, Spain and European Regional Development Fund; RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research (BMBF); Danish Cancer Society; Catalan Institute of Oncology, Spain; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra; ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain; Cancer Research UK; Medical Research Council, United Kingdom; The Hellenic Health Foundation, Greece; Italian Association for Research on Cancer (AIRC); Italian National Research Council; Fondazione-Istituto Banco Napoli, Italy; Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Helga-Nordic Center of Excellence Programme in Nutrition and Health; French League against Cancer (LNCC); National Institute for Health and Medical Research (INSERM), France; Mutuelle Generale de l'Education Nationale (MGEN), France; 3 M Co., France; Gustave Roussy Institute (IGR), France; and General Councils of France.
Published: 2014

60. Nutrient Patterns and Their Food Sources in an International Study Setting: Report from the EPIC Study

Author: Andrea Wendt, Joline W.J. Beulens, H. Bas Bueno-de-Mesquita, Pilar Amiano, Stephanie E. Chiuve, Elio Riboli, Anette Hjartåker, Domenico Palli, Isabel Drake, Pietro Ferrari, Anne Tjønneland, Maria Santucci de Magistris, Esther Molina-Montes, Heinz Freisling, Timothy J. Key, Aurelio Barricarte Gurrea, Aurelie Moskal, Jytte Halkjær, Brian Buijsse, Carlotta Sacerdote, Valeria Pala, Philippos Orfanos, Pedro T. Pisa, Tilman Kühn, Heiner Boeing, Antonia Trichopoulou, José María Huerta Castaño, José Ramón Quirós, Ulrika Ericson, Lena Maria Nilsson, Elisabete Weiderpass, Anna Winkvist, Genevieve Buckland, Nadia Slimani, Laura Nailler, Marleen A. H. Lentjes, Anne-Claire Vergnaud, Marie-Christine Boutron-Ruault, Graham Byrnes, Kay-Tee Khaw, Christina C. Dahm, Christina Bamia, Claire Cadeau, Marga C. Ocké, Dora Romaguera, Rosario Tumino, Epidemiology and Data Science, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, APH - Health Behaviors & Chronic Diseases, [Moskal,A, Pisa,PT, Freisling,H, Slimani,N] Dietary Exposure Assessment Group, International Agency for Research on Cancer, Lyon, France. [Ferrari,P] Nutritional Epidemiology Group, International Agency for Research on Cancer, Lyon, France. [Byrnes,G] Biostatistics Group, International Agency for Research on Cancer, Lyon, France. [Boutron-Ruault,M, Cadeau,C, Nailler,L] Center for research in Epidemiology and Population Health, Nutrition, Hormones and Women’s Health, INSERM, Villejuif, France. Université Paris Sud, Villejuif, France. Institut Gustave-Roussy, Villejuif, France. [Wendt,A, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. [Boeing,H, Buijsse,B] Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany. [Tjønneland,A, Halkjær,J] Danish Cancer Society Research Center, Diet, Genes and Environment, Copenhagen, Denmark. [Dahm,CC] Section for Epidemiology, Institute of Public Health, Aarhus University, Aarhus, Denmark. [Chiuve,SE] Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America. [Quirós,JR] Public Health and Health Planning Directorate, Asturias, Spain. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Barcelona, Spain. [Molina-Montes,E] Andalusian School of Public Health, Granada, Spain. [Amiano,P, Huerta,JM, Barricarte,A] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Madrid, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BIODonostia Research Institute, San Sebastian, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Khaw,K, Lentjes,MA] Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. [Key,TJ] Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. [Romaguera,D, Vergnaud,A, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. [Romaguera,D] CIBER Fisiopatología de la Obesidad y Nutrición, Madrid, Spain. [Trichopoulou,A, Bamia,C, Orfanos,P] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of AthensMedical School, Athens, Greece. Hellenic Health Foundation, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute ISPO, Florence, Italy. [Pala,V] Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, ‘‘Civile - M.P. Arezzo’’ Hospital, Ragusa, Italy. [Sacerdote,C] HuGeF Foundation and Center for Cancer Prevention CPOPiemonte, Torino, Italy. [Magistris,MS] Department of Clinical and ExperimentalMedicine, Federico II University, Naples, Italy. [Bueno-de-Mesquita,HB, Ocké,MC] The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB] Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands. [Beulens,JWJ] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Ericson,U] Diabetes and cardiovascular Disease, Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden. [Drake,I] Department of Clinical Sciences in Malmö, Research Group in Nutritional Epidemiology, Lund University, Malmö, Sweden. [Nilsson,LM] Department of Public Health and Clinical Medicine, Nutrition Research, Umea University, Umea, Sweden. [Winkvist,A] Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg, 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. [Hjartaker,A] Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Funding: The coordination of EPIC is 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 Ge´ne´ rale de l’Education Nationale, Institut National de la Sante´ et de la Recherche Me´dicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC) 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), [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, Spanish Regional Governments of Andalucı´a, Asturias, Basque Country, Murcia [no. 6236] and Navarra and the Catalan Institute of Oncology, ISCIII RETIC [RD06/0020] (Spain), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Ska°ne and Va¨sterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (United Kingdom)., and 16491, Cancer Research UK, United Kingdom
Subjects: Male, Epidemiology, EXPLORATORY FACTOR-ANALYSIS, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], VDP::Medical disciplines: 700::Health sciences: 800::Nutrition: 811, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Surveys and Questionnaires, estudios prospectivos, Estudios prospectivos, Public and Occupational Health, Food science, Prospective Studies, Cuestionarios, lcsh:Science, mediana edad, Evaluación nutricional, Disciplines and Occupations::Natural Science Disciplines::Science::Research [Medical Subject Headings], 0303 health sciences, anciano, dieta, Geographicals::Geographic Locations::Europe [Medical Subject Headings], Vitamins, adulto, Explained variation, Food Analysis, 3. Good health, DIETARY PATTERNS, Näringslära, Micronutrient Deficiencies, 030220 oncology & carcinogenesis, estilo de vida, Physical Sciences, Science & Technology - Other Topics, evaluación nutricional, Statistics (Mathematics), Check Tags::Male [Medical Subject Headings], factores socioeconómicos, Biostatistics, Endocrinology and Diabetes, Technology, Industry, Agriculture::Food and Beverages::Food [Medical Subject Headings], Estilo de vida, VDP::Medisinske Fag: 700::Helsefag: 800::Ernæring: 811, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], BREAST-CANCER, Humans, Statistical Methods, Life Style, Aged, conducta alimentaria, Science & Technology, MULTIDISCIPLINARY SCIENCES, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, lcsh:R, OLDER EUROPEANS, Biology and Life Sciences, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], Food Patterns, LARYNGEAL-CANCER, Check Tags::Female [Medical Subject Headings], Food, lcsh:Q, EUROPEAN COUNTRIES, Mathematics, análisis de alimentos, 030309 nutrition & dietetics, Animal food, humanos, lcsh:Medicine, COLORECTAL-CANCER, Nutrient, Alimentos, Medicine and Health Sciences, Public Health Surveillance, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Food Analysis [Medical Subject Headings], RISK, 2. Zero hunger, Nutrition and Dietetics, Multidisciplinary, Nutritional Deficiencies, Factores socioeconómicos, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Food Habits [Medical Subject Headings], Middle Aged, European Prospective Investigation into Cancer and Nutrition, PRINCIPAL COMPONENTS, Europe, Hábitos alimenticios, Principal component analysis, Investigación, Epidemiological Methods and Statistics, Female, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys::Diet Surveys [Medical Subject Headings], Europa, Cancer Epidemiology, Research Article, Adult, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Context (language use), Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Biology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Nutrition Assessment [Medical Subject Headings], Environmental health, Confidence Intervals, Vigilancia en salud pública, vigilancia en salud pública, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Nutrition, Nutrients, Feeding Behavior, Diet, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Nutrition Assessment, Socioeconomic Factors, GASTRIC-CANCER
Abstract: Background: Compared to food patterns, nutrient patterns have been rarely used particularly at international level. We studied, in the context of a multi-center study with heterogeneous data, the methodological challenges regarding pattern analyses. Methodology/Principal Findings: We identified nutrient patterns from food frequency questionnaires (FFQ) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study and used 24-hour dietary recall (24-HDR) data to validate and describe the nutrient patterns and their related food sources. Associations between lifestyle factors and the nutrient patterns were also examined. Principal component analysis (PCA) was applied on 23 nutrients derived from country-specific FFQ combining data from all EPIC centers (N = 477,312). Harmonized 24-HDRs available for a representative sample of the EPIC populations (N = 34,436) provided accurate mean group estimates of nutrients and foods by quintiles of pattern scores, presented graphically. An overall PCA combining all data captured a good proportion of the variance explained in each EPIC center. Four nutrient patterns were identified explaining 67% of the total variance: Principle component (PC) 1 was characterized by a high contribution of nutrients from plant food sources and a low contribution of nutrients from animal food sources; PC2 by a high contribution of micro-nutrients and proteins; PC3 was characterized by polyunsaturated fatty acids and vitamin D; PC4 was characterized by calcium, proteins, riboflavin, and phosphorus. The nutrients with high loadings on a particular pattern as derived from country-specific FFQ also showed high deviations in their mean EPIC intakes by quintiles of pattern scores when estimated from 24-HDR. Center and energy intake explained most of the variability in pattern scores. Conclusion/Significance: The use of 24-HDR enabled internal validation and facilitated the interpretation of the nutrient patterns derived from FFQs in term of food sources. These outcomes open research opportunities and perspectives of using nutrient patterns in future studies particularly at international level., The coordination of EPIC is 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 Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) 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); [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, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia [no. 6236] and Navarra and the Catalan Institute of Oncology, ISCIII RETIC [RD06/0020] (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skane and Vasterbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (United Kingdom). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Published: 2014

61. DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author: Osorio, Ana, Milne, Roger L., Kuchenbaecker, Karoline, Vaclová, Tereza, Pita, Guillermo, Alonso, Rosario, Peterlongo, Paolo, Blanco Guillermo, Ignacio, De la Hoya, Miguel, Durán, Mercedes, Diez, Orland, Ramon y Cajal, Teresa, Konstantopoulou, Irene, Martínez-Bouzas, Cristina, Andrés Conejero, Raquel, Soucy, Penny, McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, SWE-BRCA, None, Arver, Brita, Rantala, Johanna, Loman, Niklas, Ehrencrona, Hans, Olopade, Olufunmilayo I., Beattie, Mary S., Domchek, Susan M., Nathanson, Katherine, Rebbeck, Timothy R., Arun, Banu K., Karlan, Beth Y., Walsh, Christine, Lester, Jenny, John, Esther M., Whittemore, Alice S., Daly, Mary B., Southey, Melissa, Hopper, John L, Terry, Mary Beth, Buys, Saundra, Janavicius, Ramunas, Dorfling, Cecilia M., van Rensburg, Elizabeth J., Steele, Linda, Neuhausen, Susan L., Ding, Yuan Chun, Hansen, Thomas v. O., Jønson, Lars, Ejlertsen, Bent, Gerdes, Anne-Marie, Infante, Mar, Herráez, Belén, Moreno, Leticia Thais, Weitzel, Jeffrey N., Herzog, Josef, Weeman, Kisa, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Scuvera, Giulietta, Bonanni, Bernardo, Mariette, Frederique, Volorio, Sara, Viel, Alessandra, Varesco, Liliana, Papi, Laura, Ottini, Laura, Tibiletti, Maria Grazia, Radice, Paolo, Yannoukakos, Drakoulis, Garber, Judy, Ellis, Steve, Frost, Debra, Platte, Radka, Fineberg, Elena, Evans, Gareth, Lalloo, Fiona, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Eccles, Diana M, Cook, Jackie, Hodgson, Shirley, Brewer, Carole, Tischkowitz, Marc, Douglas, Fiona, Porteous, Mary, Side, Lucy, Walker, Lisa, Morrison, Patrick, Donaldson, Alan, Kennedy, John, Foo, Claire, Godwin, Andrew K., Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hans Jörg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Gehrig, Andrea, Stoppa-Lyonnet, Dominique, Sinilnikova, Olga M., Mazoyer, Sylvie, Damiola, Francesca, Poppe, Bruce, Claes, Kathleen, Piedmonte, Marion, Tucker, Kathy, Backes, Floor, Rodríguez, Gustavo, Brewster, Wendy, Wakeley, Katie, Rutherford, Thomas, Caldes, Trinidad, Nevanlinna, Heli, Aittomäki, Kristiina, Rookus, Matti A., van Os, Theo A. M., van der Kolk, Lizet, de Lange, J. L., Meijers-Heijboer, Hanne E. J., van der Hout, A. H., van Asperen, Christi J., Gómez Garcia, Encarna B., Hoogerbrugge, Nicoline, Collée, J. Margriet, van Deurzen, Carolien H. M., van der Luijt, Rob B., Devilee, Peter, HEBON, None, Olah, Edith, Lázaro, Conxi, Teulé, Alex, Menéndez, Mireia, Jakubowska, Anna, Cybulski, Cezary, Gronwald, Jacek, Lubinski, Jan, Durda, Katarzyna, Jaworska-Bieniek, Katarzyna, Johannsson, Oskar Th., Maugard, Christine, Montagna, Marco, Tognazzo, Silvia, Teixeira, Manuel R., Healey, Sue, Investigators, kConFab, Olswold, Curtis, Guidugli, Lucia, Lindor, Noralane, Slager, Susan, Szabo, Csilla I., Vijai, Joseph, Robson, Mark, Kauff, Noah, Zhang, Liying, Rau-Murthy, Rohini, Fink-Retter, Anneliese, Singer, Christian F., Rappaport, Christine, Geschwantler Kaulich, Daphne, Pfeiler, Georg, Tea, Muy-Kheng, Berger, Andreas, Phelan, Catherine M., Greene, Mark H., Mai, Phuong L., Lejbkowicz, Flavio, Andrulis, Irene L., Mulligan, Anna Marie, Glendon, Gord, Toland, Amanda Ewart, Bojesen, Anders, Pedersen, Inge Sokilde, Sunde, Lone, Thomassen, Mads, Kruse, Torben A., Jensen, Uffe Birk, Friedman, Eitan, Laitman, Yael, Shimon, Shani Paluch, Simard, Jacques, Easton, Douglas F., Offit, Kenneth, Couch, Fergus J., Chenevix-Trench, Georgia, Antoniou, Antonis C., Benitez, Javier, Universitat Autònoma de Barcelona, Pediatric Surgery, Clinical Genetics, Pathology, Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain, Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain. 2Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. 3Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. 4Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain. 5Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain. 6IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. 7Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. 8Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid, Spain. 9Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain. 10Oncogenetics Laboratory, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Institut de Recerca (VHIR), and Universitat Autonoma de Barcelona, Barcelona, Spain. 11Oncology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 12Molecular Diagnostics Laboratory IRRP, National Centre for Scientific Research Demokritos Aghia Paraskevi Attikis, Athens, Greece. 13Molecular Genetics Laboratory (Department of Biochemistry), Cruces Hospital Barakaldo, Bizkaia, Spain. 14Medical Oncology Service, Hospital Clínico Lozano Blesa, San Juan Bosco, Zaragoza, Spain. 15Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Canada. 16Department of Oncology, Lund University, Lund, Sweden. 17Department of Oncology, Karolinska University Hospital, Stockholm, Sweden. 18Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. 19Department of Oncology, Lund University Hospital, Lund, Sweden. 20Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. 21Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois, United States of America. 22Departments of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco, San Francisco, California, United States of America. 23Abramson Cancer Center and Department of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America. 24Abramson Cancer Center and Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America. 25University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. 26Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America. 27Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California, United States of America. 28Department of Health Research & Policy, Stanford University School of Medicine, Stanford, California, United States of America. 29Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America. 30Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, Australia. 31Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, Victoria, Australia. 32Department of Epidemiology, Columbia University, New York, New York, United States of America. 33Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, United States of America. 34Vilnius University Hospital Santariskiu Clinics, Hematology, oncology and transfusion medicine center, Department of Molecular and Regenerative Medicine, Vilnius, Lithuania. 35Department of Genetics, University of Pretoria, Pretoria, South Africa. 36Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, United States of America. 37Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 38Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 39Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 40Clinical Cancer Genetics, City of Hope, Duarte, California, United States of America. 41Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy. 42Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy. 43IFOM, Fondazione Istituto FIRC di Oncologia Molecolare and Cogentech Cancer Genetic Test Laboratory, Milan, Italy. 44Division of Experimental Oncology 1, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy. 45Unit of Hereditary Cancer, Department of Epidemiology, Prevention and Special Functions, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. 46Unit of Medical Genetics, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy. 47Department of Molecular Medicine, 'Sapienza' University, Rome, Italy. 48UO Anatomia Patologica, Ospedale di Circolo-Università dell'Insubria, Varese, Italy. 49Unit of Molecular bases of genetic risk and genetic testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy. 50Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America. 51Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom. 52South East Thames Regional Genetics Service, Guy's Hospital London, United Kingdom. 53Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom. 54Yorkshire Regional Genetics Service, Leeds, United Kingdom. 55Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Glasgow, United Kingdom. 56West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, United Kingdom. 57Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, United Kingdom. 58Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, United Kingdom. 59Clinical Genetics Department, St Georges Hospital, University of London, London, United Kingdom. 60Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, United Kingdom. 61Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, United Kingdom. 62Institute of Human Genetics, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom. 63South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, United Kingdom. 64North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom. 65Oxford Regional Genetics Service, Churchill Hospital, Oxford, United Kingdom. 66Northern Ireland Regional Genetics Centre, Belfast City Hospital, Belfast, United Kingdom. 67South West Regional Genetics Service, Bristol, United Kingdom. 68Academic Unit of Clinical and Molecular Oncology, Trinity College Dublin and St James's Hospital, Dublin, Eire. 69Cheshire & Merseyside Clinical Genetics Service, Liverpool Women's NHS Foundation Trust, Liverpool, United Kingdom. 70Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America. 71Centre of Familial Breast and Ovarian Cancer and Centre for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany. 72Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany. 73Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. 74Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. 75Institute of Human Genetics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. 76Department of Gynaecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. 77Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany. 78Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany. 79Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany. 80Institute of Human Genetics, University of Münster, Münster, Germany. 81Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. 82Institute of Human Genetics, Campus Virchov Klinikum, Charite Berlin, Berlin, Germany. 83Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University Würzburg, Würzburg, Germany. 84Institut Curie, Department of Tumour Biology, Paris, France, Institut Curie, INSERM U830, Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 85Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon - Centre Léon Bérard, Lyon, France, INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France. 86INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France. 87Center for Medical Genetics, Ghent University, Ghent, Belgium. 88Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, New York, United States of America. 89Prince of Wales Hospital. Sydney, Australia. 90Ohio State University, Columbus Cancer Council, Columbus, Ohio, United States of America. 91Division of Gynecologic Oncology, NorthShore University HealthSystem, Evanston, Illinois, United States of America. 92Division of Gynecologic Oncology, NorthShore University HealthSystem, Chicago, Illinois, United States of America. 93For Tufts Medical Center, Boston, Massachusetts, United States of America. 94Yale University School of Medicine, New Haven, Connecticut, United States of America. 95Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. 96Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 97Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands. 98Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands. 99Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands. 100University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands. 101Department of Clinical Genetics, Leiden University Medical Center Leiden, Leiden, The Netherlands. 102Department of Clinical Genetics and GROW, School for Oncology and Developmental Biology, MUMC, Maastricht, The Netherlands. 103Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 104Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands. 105Department of Pathology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands. 106Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. 107Department of Human Genetics & Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. 108The Hereditary Breast and Ovarian Cancer Research Group, Netherlands Cancer Institute, Amsterdam, The Netherlands. 109Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary. 110Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. 111Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. 112Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland. 113Department of Oncology, Landspitali University Hospital and BMC, Faculty of Medicine, University of Iceland, Reykjavik Iceland. 114Laboratoire de Diagnostic Génétique et Service d'Onco-hématologie, Hopitaux Universitaire de Strasbourg, CHRU Nouvel Hôpital Civil, Strasbourg, France. 115Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy. 116Department of Genetics, Portuguese Oncology Institute, Porto, and Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal. 117Department of Genetics and Computational Biology, Queensland Institute of Medical Research, Brisbane, Australia. 118Kathleen Cuningham Consortium for Research into Familial Breast Cancer, Peter MacCallum Cancer Center, Melbourne, Australia. 119Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America. 120Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America. 121Center for Individualized Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America. 122Center for Translational Cancer Research, Department of Biological Sciences, University of Delaware, Newark, Delaware, United States of America. 123Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. 124Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. 125Diagnostic Molecular Genetics Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. 126Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 127Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, United States of America. 128Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America. 129Clalit National Israeli Cancer Control Center, Haifa, Israel. 130Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, and Cancer Care Ontario, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. 131Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada. 132Ontario Cancer Genetics Network: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. 133Division of Human Cancer Genetics, Departments of Internal Medicine and Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America. 134Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark. 135Section of Molecular Diagnostics, Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark. 136Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark. 137Department of Clinical Genetics, Odense University Hospital, Odense, Denmark. 138Sheba Medical Center, Tel Aviv, Israel. 139Canada Research Chair in Oncogenetics, Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Canada. 140Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America. 141Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain, Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain, Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain., SWE-BRCA, Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Unión Europea, Cancer Research UK (Reino Unido), United States of Department of Health & Human Services, Canadian Institutes of Health Research, Susan G. Komen Breast Cancer Foundation, Ralph and Marion Falk Medical Research Trust, Research Council (Lituania), University of Kansas. Cancer Center (Estados Unidos), National Institute for Health Research (Reino Unido), Deutsche Krebshilfe, Finlands Akademi (Finlandia), Dutch Cancer Society (Holanda), Dutch Research Council (Holanda), Pink Ribbons Project, Hungarian Scientific Research Fund (Hungría), Canadian Breast Cancer Network, Ministère du Développement économique, de Innovation et de Exportation (Canadá), Westat (Estados Unidos), Department of Obstetrics and Gynecology, Clinicum, Universitat de Barcelona, Human Genetics, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Lee, Andrew [0000-0003-0677-0252], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Human genetics, CCA - Oncogenesis, Fundación Mutua Madrileña Automovilista, Fundacion Asociacion Espanola Contra el Cancer (AECC), Instituto de Salud Carlos III - ISCIII, European Union (EU), Cancer Research UK, United States Department of Health & Human Services National Institutes of Health (NIH) - USA, Canadian Institutes of Health Research (CIHR), Research Council of Lithuania, University of Kansas Cancer Center, National Institute for Health Research (NIHR), Academy of Finland, KWF Kankerbestrijding, Netherlands Organization for Scientific Research (NWO), Pink Ribbon grant, Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA), Canadian Breast Cancer Research Alliance-grant, Ministry of Economic Development, Innovation and Export Trade, and Westat, Inc, Rockville, MD
Subjects: Cancer Research, 24 Ciencias de la Vida, DNA Repair, endocrine system diseases, ADN, Càncer d'ovari, Synthetic lethality, BRCA1 Protein/genetics, DNA Glycosylases, 0302 clinical medicine, DNA Glycosylases/genetics, Brjóstakrabbamein, Genotype, Medicine and Health Sciences, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Glicosilasas, INVESTIGATORS, skin and connective tissue diseases, OGG1, Genetics (clinical), Genetics, DAMAGE, Aged, 80 and over, Ovarian Neoplasms, 0303 health sciences, BRCA1 Protein, SINGLE-NUCLEOTIDE POLYMORPHISMS, COMMON VARIANTS, Base excision repair, Middle Aged, BRCA2 Protein, 3. Good health, 030220 oncology & carcinogenesis, NEIL2, Female, Medical Genetics, Research Article, BRCA1, BRCA2, Adult, Risk, Ovarian Neoplasms/genetics, lcsh:QH426-470, Adolescent, DNA repair, education, Single-nucleotide polymorphism, Breast Neoplasms, DNA Repair/genetics, Biology, Breast Neoplasms/genetics, Polymorphism, Single Nucleotide, OVARIAN-CANCER, 03 medical and health sciences, Polymorphism, Single Nucleotide/genetics, SDG 3 - Good Health and Well-being, Ovarian cancer, Cancer Genetics, BREAST-CANCER, Humans, Genetic Predisposition to Disease, ddc:610, Molecular Biology, Gene, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Aged, BRCA2 Protein/genetics, CONSORTIUM, Biology and Life Sciences, Arfgengi, lcsh:Genetics, DNA glycosylase, Cancer research, 3111 Biomedicine, GENETIC MODIFIERS, Genètica
Abstract: Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p, Author Summary Women harboring a germ-line mutation in the BRCA1 or BRCA2 genes have a high lifetime risk to develop breast and/or ovarian cancer. However, not all carriers develop cancer and high variability exists regarding age of onset of the disease and type of tumor. One of the causes of this variability lies in other genetic factors that modulate the phenotype, the so-called modifier genes. Identification of these genes might have important implications for risk assessment and decision making regarding prevention of the disease. Given that BRCA1 and BRCA2 participate in the repair of DNA double strand breaks, here we have investigated whether variations, Single Nucleotide Polymorphisms (SNPs), in genes participating in other DNA repair pathway may be associated with cancer risk in BRCA carriers. We have selected the Base Excision Repair pathway because BRCA defective cells are extremely sensitive to the inhibition of one of its components, PARP1. Thanks to a large international collaborative effort, we have been able to identify at least two SNPs that are associated with increased cancer risk in BRCA1 and BRCA2 mutation carriers respectively. These findings could have implications not only for risk assessment, but also for treatment of BRCA1/2 mutation carriers with PARP inhibitors.
Published: 2014

62. Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection

Author: Jaroslaw Grobelny, Mikolaj Donten, Malgorzata Krzyzowska, Justyna Sokołowska, Grzegorz Celichowski, Marianna Gniadek, Julita Nowakowska, Emilia Tomaszewska, Zuzanna Nowak, Piotr Orlowski, Piotr Baska, Military Institute of Hygiene and Epidemiology, Department of Regenerative Medicine, University of Lodz, Faculty of Chemistry, University of Warsaw, and Warsaw University of Life Sciences
Subjects: Chemokine, Herpesvirus 2, Human, Gynecologic Infections, Metal Nanoparticles, medicine.disease_cause, Silver nanoparticle, Mice, chemistry.chemical_compound, Chlorocebus aethiops, Medicine and Health Sciences, Nanotechnology, Infectivity, Multidisciplinary, Obstetrics and Gynecology, Engineering and Technology, Cytokines, Medicine, Female, Research Article, Silver, Science, Virus Attachment, Microbial Sensitivity Tests, macromolecular substances, Biology, Microbiology, Antiviral Agents, Virus, Cell Line, In vivo, Virology, Tannic acid, medicine, Animals, Inflammation, Dose-Response Relationship, Drug, Biology and Life Sciences, Herpes Simplex, Virus Internalization, In vitro, Disease Models, Animal, Herpes simplex virus, chemistry, biology.protein, Nanoparticles, Women's Health, Tannins
Abstract: The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections. This work was supported by the Polish National Science Centre grant No. 2011/03/B/NZ6/04878 (for MK) and Centre for Preclinical Research and Technology (CePT) Project No. POIG.02.02.00-14-024/08-0 (for MG and MD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Published: 2014

63. Combined impact of healthy lifestyle factors on colorectal cancer : a large European cohort study

Author: Domenico Palli, Aurelio Barricarte, José Ramón Quirós, Laureen Dartois, Heather Ward, Salvatore Panico, Isabelle Romieu, Veronika Fedirko, Ulrika Ericson, Kim Overvad, Miren Dorronsoro, Pagona Lagiou, Krasimira Aleksandrova, Rudolf Kaaks, Kay-Tee Khaw, Anne Tjønneland, Elio Riboli, Laure Dossus, Sabina Rinaldi, Ingrid Ljuslinder, Genevieve Buckland, Marc J. Gunter, Petra H.M. Peeters, Vittorio Krogh, Alessio Naccarati, Ingegerd Johansson, Bodil Ohlsson, Peter D. Siersema, Kathryn E. Bradbury, Heiner Boeing, María José Sánchez, Mazda Jenab, Antonia Trichopoulou, H. Bas Bueno-de-Mesquita, Elisabete Weiderpass, Guri Skeie, Kristin Benjaminsen Borch, Tobias Pischon, Sven Knüppel, Teresa Norat, Nicholas J. Wareham, Joyce Kong, Dora Romaguera, Kuanrong Li, Dimitrios Trichopoulos, Rosario Tumino, Marie-Christine Boutron-Ruault, María Dolores Chirlaque, [Aleksandrova,K, Knüppe,S, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Pischon,T] Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany. [Jenab,M, Fedirko,V, Rinald,S, Romieu,I, Kong,J] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, the Netherlands. [Bueno-de-Mesquita,HB, Norat,T, Romaguera,D, Peeters,PHM, Gunter,MJ, Ward,HA, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA. [Romaguera,D] Instituto de Investigacion Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, Spain. [Boutron-Ruault,M, Dossus,L, Dartois,L] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. Univ Paris Sud, Villejuif, France. IGR, Villejuif, France. [Kaaks,R, Li,K] Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Tjønneland,K] Diet, Genes and Environment Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain. [Sánchez,MJ, Chirlaque,M] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Dorronsoro,M] Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain. [Chirlaque,M] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] Clinical Gerontology Unit, Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Bradbury,KE] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'M.P.Arezzo' Hospital, Ragusa, Italy. [Naccarati,A] HuGeF - Human Genetics Foundation – Torino, Molecular and Genetic Epidemiology Unit, Turin, Italy. [Panico,S] Department of clinical and experimental medicine-Federico II University, Naples, Italy. [Peeters,PHM] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherland. [Ljuslinder,I] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [Johansson,I] Department of Odontology, Umeå University, Umeå, Sweden. [Ericson,U] Diabetes and Cardiovascular Disease, Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden. [Ohlsson,B] Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital Malmö, Lund University, Malmö, Sweden. [Weiderpass,E, Skeie,G, Borch,KB] Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland., The coordination of the EPIC study 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 Générale de l¿Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa and AVIS Ragusa (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), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health, Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway), Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council (United Kingdom)., Aleksandrova, Krasimira, Pischon, Tobia, Jenab, Mazda, Bueno de Mesquita, H. Ba, Fedirko, Veronika, Norat, Teresa, Romaguera, Dora, Knüppel, Sven, Boutron Ruault, Marie Christine, Dossus, Laure, Dartois, Laureen, Kaaks, Rudolf, Li, Kuanrong, Tjønneland, Anne, Overvad, Kim, Quirós, José Ramón, Buckland, Genevieve, Sánchez, María José, Dorronsoro, Miren, Chirlaque, Maria Dolore, Barricarte, Aurelio, Khaw, Kay Tee, Wareham, Nicholas J, Bradbury, Kathryn E, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Naccarati, Alessio, Panico, Salvatore, Siersema, Peter D, Peeters, Petra H. M, Ljuslinder, Ingrid, Johansson, Ingegerd, Ericson, Ulrika, Ohlsson, Bodil, Weiderpass, Elisabete, Skeie, Guri, Borch, Kristin Benjaminsen, Rinaldi, Sabina, Romieu, Isabelle, Kong, Joyce, Gunter, Marc J, Ward, Heather A, Riboli, Elio, and Boeing, Heiner
Subjects: Male, consumo de alcohol, Health Behavior, 0302 clinical medicine, estudios prospectivos, European Prospective Investigation into Cancer and, Prospective Studies, estudios de cohortes, mediana edad, PROPORTION, anciano, education.field_of_study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activity [Medical Subject Headings], dieta, Incidence, COLON-CANCER, Hazard ratio, lifestyle factors, General Medicine, adulto, 3. Good health, estilo de vida, 030220 oncology & carcinogenesis, Cohort, acrylamide, Dieta, Cohort study, Human, medicine.medical_specialty, Alcohol Drinking, European Continental Ancestry Group, Lifestyles, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], European Prospective Investigation into Cancer and Nutrition (EPIC), Endocrinology and Diabetes, dietary questionnaires, haemoglobin adducts, incidencia, White People, 03 medical and health sciences, Càncer colorectal, population attributable risks, Humans, education, Life Style, METAANALYSIS, Aged, Cancer och onkologi, Science & Technology, Proportional hazards model, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, biomarkers, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], PREVENTION, Prospective Studie, MYOCARDIAL-INFARCTION, ATTRIBUTABLE RISK, Cardiovascular and Metabolic Diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], RISK-FACTORS, Proportional Hazards Model, grupo de ascendencia continental europea, measurement errors, Gerontology, colorectal cancer, combined impact, modelos de riesgos proporcionales, humanos, Colorectal Neoplasm, Cohort Studies, Risk Factors, Neoplasias colorrectales, Hábito de fumar, 030212 general & internal medicine, Prospective cohort study, conducta sanitaria, Medicine(all), Consumo de alcohol, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Europe, NUTRITION, Female, Colorectal Neoplasms, Life Sciences & Biomedicine, Research Article, Adult, Estils de vida, neoplasias colorrectales, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], smoking, Medicine, General & Internal, General & Internal Medicine, Internal medicine, medicine, factores de riesgo, Proportional Hazards Models, Nutrition (EPIC), RECTAL CANCERS, business.industry, Risk Factor, Diet, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, PHYSICAL-ACTIVITY, Attributable risk, Cohort Studie, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract: Background: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. Results: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend, The coordination of the EPIC study 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 Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa and AVIS Ragusa (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); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health, Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway); Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skane and Vasterbotten (Sweden); Cancer Research UK, Medical Research Council (United Kingdom).
Published: 2014

64. Personality and all-cause mortality: individual-participant meta-analysis of 3,947 deaths in 76,150 adults

Author: Hermann Nabi, Marianna Virtanen, G. David Batty, Mika Kivimäki, Archana Singh-Manoux, Solja T. Nyberg, Markus Jokela, Department of Psychology, University of Cambridge [UK] (CAM), Department of Epidemiology and Public Health, University College of London [London] (UCL), Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Finnish Institute of Occupational Health, 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), This research was supported by the Academy of Finland (grants 124322, 124271, and 132944), the Bupa Founda- tion, United Kingdom, the Medical Research Council (grant K013351), the National Institutes of Health ( grants R01HL036310 and R01AG034454), the New Occupational Safety and Health ERA Research Program, and the Finnish Work Environment Fund. The Centre for Cognitive Ageing and Cognitive Epidemiology is supported by the Biotech- nology and Biological Sciences Research Council, the Engi- neering and Physical Sciences Research Council, the Economic and Social Research Council, the Medical Research Council, and the University of Edinburgh as part of the cross-council Lifelong Health and Wellbeing Initiative. G.D.B. is a Well- come Trust Fellow. M.V. is an Academy of Finland Research Fellow (grant 258598). M.K. is an Economic and Social Research Council Professor., SZTAJNBOK, Pascale, and 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)
Subjects: Agreeableness, Gerontology, MESH: Socioeconomic Factors, Epidemiology, media_common.quotation_subject, 050109 social psychology, psychology, survival analysis, 03 medical and health sciences, 0302 clinical medicine, MESH: Sex Factors, MESH: Risk Factors, MESH: Personality, Openness to experience, Medicine, Personality, 0501 psychology and cognitive sciences, 030212 general & internal medicine, Big Five personality traits, MESH: Cohort Studies, media_common, MESH: Age Factors, Extraversion and introversion, MESH: Humans, MESH: Middle Aged, MESH: Mortality, business.industry, 05 social sciences, Conscientiousness, Neuroticism, mortality, MESH: Male, MESH: Prospective Studies, 3. Good health, meta-analysis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, personality, MESH: Extraversion (Psychology), MESH: Anxiety Disorders, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Systematic Reviews and Meta- and Pooled Analyses, MESH: Female, Cohort study
Abstract: International audience; Personality may influence the risk of death, but the evidence remains inconsistent. We examined associations between personality traits of the five-factor model (extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience) and the risk of death from all causes through individual-participant meta-analysis of 76,150 participants from 7 cohorts (the British Household Panel Survey, 2006-2009; the German Socio-Economic Panel Study, 2005-2010; the Household, Income and Labour Dynamics in Australia Survey, 2006-2010; the US Health and Retirement Study, 2006-2010; the Midlife in the United States Study, 1995-2004; and the Wisconsin Longitudinal Study's graduate and sibling samples, 1993-2009). During 444,770 person-years at risk, 3,947 participants (54.4% women) died (mean age at baseline = 50.9 years; mean follow-up = 5.9 years). Only low conscientiousness-reflecting low persistence, poor self-control, and lack of long-term planning-was associated with elevated mortality risk when taking into account age, sex, ethnicity/nationality, and all 5 personality traits. Individuals in the lowest tertile of conscientiousness had a 1.4 times higher risk of death (hazard ratio = 1.37, 95% confidence interval: 1.18, 1.58) compared with individuals in the top 2 tertiles. This association remained after further adjustment for health behaviors, marital status, and education. In conclusion, of the higher-order personality traits measured by the five-factor model, only conscientiousness appears to be related to mortality risk across populations.
Published: 2013

65. High-throughput analysis of antimalarial susceptibility data by the WorldWide Antimalarial Resistance Network (WWARN) in vitro analysis and reporting tool

Author: Jacob D. Johnson, Véronique Sinou, Sabina Dahlström, Claribel Murillo, Harald Noedl, Jacques Le Bras, François Nosten, Jennifer A. Flegg, Carol Hopkins Sibley, Bruno Pradines, Neils B. Quashie, Charles J. Woodrow, Pharath Lim, Lise Musset, Philippe J Guerin, Sam L. Nsobya, Kanlaya Sriprawat, Hervé Le Nagard, Richard Cooksey, Didier Menard, Rick M. Fairhurst, Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University [Bangkok], WorldWide Antimalarial Resistance Network In Vitro Module (WWARN), Hôpital Bichat-Claude Bernard, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), International Center for Medical Research and Training (CIDEIM), International Center for Medical Research and Training, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Institut Pasteur de la Guyane, Laboratoire de Parasitologie [Cayenne, Guyane française], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Epidemiology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, National Center for Parasitology, Entomology and Malaria Control, National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Department of Medicine, Makerere University [Kampala, Ouganda] (MAK), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Institute of Specific Prophylaxis and Tropical Medicine, Medizinische Universität Wien = Medical University of Vienna, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence du Paludisme, U.S. Army Medical Research Unit, Kenya, Walter Reed Project, Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), WWARN is supported by a Bill and Melinda Gates Foundation grant. This work was supported in part by the Intramural Research Program of NIAID, NIH, WorldWide Antimalarial Resistance Network, Nuffield Department of Clinical Medicine ( WWARN ), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, WorldWide Antimalarial Resistance Network In Vitro Module ( WWARN ), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), International Center for Medical Research and Training ( CIDEIM ), Institut Pasteur du Cambodge-Réseau International des Instituts Pasteur ( RIIP ), Shoklo Malaria Research Unit, Réseau International des Instituts Pasteur ( RIIP ), Makerere University ( MAK ), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques ( IP-TPT ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Service de Santé des Armées-Université de Montpellier ( UM ), Medical University of Vienna, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes ( URMITE ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ), Department of Genome Sciences [Seattle] ( GS ), Mère et enfant face aux infections tropicales ( MERIT - UMR_D 216 ), Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ), University of Oxford [Oxford], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Shoklo Malaria Research Unit [Mae Sot, Thailand] (Faculty of Tropical Medicine), Mahidol University [Bangkok]-Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford [Oxford]-Wellcome Trust, Makerere University (MAK), and Mère et enfant face aux infections tropicales (MERIT - UMR_D 216)
Subjects: Drug, Artemisinins, Combination therapy, media_common.quotation_subject, 030231 tropical medicine, Plasmodium falciparum, Drug Resistance, Amodiaquine, Drug resistance, Pharmacology, 03 medical and health sciences, Antimalarials, 0302 clinical medicine, Parasitic Sensitivity Tests, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, High-Throughput Screening Assays, medicine, Pharmacology (medical), Artemisinin, Malaria, Falciparum, media_common, Automation, Laboratory, 0303 health sciences, Analytical Procedures, Internet, biology, Quinine, 030306 microbiology, Chloroquine, biology.organism_classification, 3. Good health, Mefloquine, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Drug Therapy, Combination, medicine.drug
Abstract: Assessment of in vitro susceptibility is a fundamental component of antimalarial surveillance studies, but wide variations in the measurement of parasite growth and the calculation of inhibitory constants make comparisons of data from different laboratories difficult. Here we describe a Web-based, high-throughput in vitro analysis and reporting tool (IVART) generating inhibitory constants for large data sets. Fourteen primary data sets examining laboratory-determined susceptibility to artemisinin derivatives and artemisinin combination therapy partner drugs were collated from 11 laboratories. Drug concentrations associated with half-maximal inhibition of growth (IC 50 s) were determined by a modified sigmoid E max model-fitting algorithm, allowing standardized analysis of 7,350 concentration-inhibition assays involving 1,592 isolates. Examination of concentration-inhibition data revealed evidence of apparent paradoxical growth at high concentrations of nonartemisinin drugs, supporting amendment of the method for calculating the maximal drug effect in each assay. Criteria for defining more-reliable IC 50 s based on estimated confidence intervals and growth ratios improved correlation coefficients for the drug pairs mefloquine-quinine and chloroquine-desethylamodiaquine in 9 of 11 and 8 of 8 data sets, respectively. Further analysis showed that maximal drug inhibition was higher for artemisinins than for other drugs, particularly in ELISA (enzyme-linked immunosorbent assay)-based assays, a finding consistent with the earlier onset of action of these drugs in the parasite life cycle. This is the first high-throughput analytical approach to apply consistent constraints and reliability criteria to large, diverse antimalarial susceptibility data sets. The data also illustrate the distinct biological properties of artemisinins and underline the need to apply more sensitive approaches to assessing in vitro susceptibility to these drugs.
Published: 2013

66. Meat consumption and mortality--results from the European Prospective Investigation into Cancer and Nutrition

Author: Pietro Ferrari, Dagrun Engeset, Timothy J. Key, Kuanrong Li, Anne Tjønneland, Kim Overvad, José María Huerta, H. Bas Bueno-de-Mesquita, Christine L. Parr, Guri Skeie, Pilar Amiano, Kay-Tee Khaw, Teresa Norat, Göran Hallmans, Anne C. Vergnaud, Isabelle Romieux, Fulvio Ricceri, M. Luisa Redondo, Dimitirios Trichopoulos, Rosario Tumino, Veronika Fedirko, Françoise Clavel-Chapelon, Elio Riboli, Androniki Naska, Rikke Egeberg, Nicholas J. Wareham, Marianne Uhre Jakobsen, Emily Sonestedt, Heiner Boeing, Aurelio Barricarte, Salvatore Panico, Max Leenders, Manuela M. Bergmann, Laura Nailler, Isabel Drake, Paula Jakszyn, Marie-Christine Boutron-Ruault, Domenico Palli, Sabine Rohrmann, Vittorio Krogh, Antonia Trichopoulou, María José Sánchez, Jakob Linseisen, Petra H.M. Peeters, Ingegerd Johansson, Francesca L. Crowe, Rudolf Kaaks, Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, University of Zurich, Rohrmann, Sabine, [Rohrmann,S] Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland. [Rohrmann,S., Li,K, Kaaks,R, Linseisen,J] Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany. [Overvad,K, Jakobsen,MU] Section of Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.[Bueno-de-Mesquita, HB, Leenders,M] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Egeberg,R, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Nailler,L, Boutron-Ruault,MC, Clavel-Chapelon,F] Inserm, Centre for Research in Epidemiology and Population Health, Institut Gustave Roussy, Villejuif, France. [Nailler,L, Clavel-Chapelon,F] Paris South University, UMRS, Villejuif, France. [Krogh,V] Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Panico,S] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civile - M.P.Arezzo' Hospital, Ragusa, Italy. [Ricceri,F] HuGeF - Human Genetics Foundation - Torino, Torino, Italy. [Bergmann,MM, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Khaw,KT] Department of Public Health and Primary Care, University of Cambridge, Cambridge UK. [Wareham,NJ] Medical Research Council (MRC) Epidemiology Unit, Cambridge UK. [Crowe,FL, Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. [Naska,A, Trichopoulou,A] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston MA, USA.Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Peeters,PHM] Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands. [Peeters,PHM, Norat,T, Vergnaud,AC, Riboli,E] School of Public Health, Imperial College, London, UK. [Engeset,D, Skeie,G] Department of Community Medicine, University of Tromsø, Tromsø, Norway. [Parr,CL] Department of Biostatistics, Faculty of Medicine, University of Oslo, Oslo, Norway. [Jakszyn,P] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain. [Sánchez,MJ, Huerta,JM] Andalusian School of Public Health, Granada, Spain. [Sánchez,MJ, Barricarte,A, Amiano,P] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Redondo,ML] Public Health Directorate Asturias, Oviedo, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Health of the Regional Government of the Basque Country, San Sebastian, Spain. [Drake,I, Sonestedt,E] Department of Clinical Sciences, Lund University, Malmö, Sweden. [Hallmans,G] Department of Public Health and Clinical Medicine, Nutrition Research, Umeå University, Umeå, Sweden. [Johansson,I] Department of Odontology, Cariology, Umeå University, Umeå, Sweden. [Fedirko,V, Romieux,I, Ferrari,P] International Agency for Research on Cancer (IARC), Lyon, France. [Linseisen,J] Institute of Epidemiology, Helmholtz Centre Munich, Neuherberg, Germany., Europe Against Cancer Program of the European Commission (SANCO), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RCESP exp. C03/09, Spain, Cancer Research UK, Medical Research Council, United Kingdom, Stroke Association, United Kingdom, British Heart Foundation, Department of Health, United Kingdom, Food Standards Agency, United Kingdom, Wellcome Trust, United Kingdom, the Hellenic Health Foundation and the Stavros Niarchos Foundation, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Fondazione-Istituto Banco Napoli, 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), Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skåne, Sweden, Nordforsk the Norwegian Cancer Society, French League against Cancer (LNCC), National Institute for Health and Medical Research (INSERM), France, Mutuelle Générale de l’Education Nationale (MGEN), France, 3M Co, France, Gustave Roussy Institute (IGR), France, and General Councils of France, BMC, Ed., Division of Cancer Epidemiology and Prevention, Universität Zürich [Zürich] = University of Zurich (UZH)-Institute of Social and Preventive Medicine, Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Section of Epidemiology, Aarhus University [Aarhus], Department of Gastroenterology and Hepatology, University Medical Centre, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Danish Cancer Society Research Center, 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), Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Department of Clinical and Experimental Medicine, University of Naples Federico II = Università degli studi di Napoli Federico II, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, HuGeF - Human Genetics Foundation - Torino, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Epidemiology Unit, Medical Research Council, Cancer Epidemiology Unit, University of Oxford, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School [Athens], Hellenic Health Foundation, Harvard School of Public Health, Bureau of Epidemiologic Research, Academy of Athens, Julius Center, University Medical Center [Utrecht], School of Public Health, Imperial College London, Department of Community Medicine, University of Tromsø (UiT), Department of Biostatistics [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO), Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), Murcia Regional Health Council, Public Health Directorate Asturias, Navarre Public Health Institute, Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Clinical Sciences, Lund University [Lund], Department of Public Health and Clinical Medicine, Umeå University, Department of Odontology, Cariology, International Agency for Cancer Research (IACR), Institute of Epidemiology, Helmholtz Centre Munich, 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), Università degli studi di Napoli Federico II, University of Oxford [Oxford], Rohrmann, S, Overvad, K, Bueno de Mesquita, Hb, Jakobsen, Mu, Egeberg, R, Tj?nneland, A, Nailler, L, Boutron Ruault, Mc, Clavel Chapelon, F, Krogh, V, Palli, D, Panico, Salvatore, Tumino, R, Ricceri, F, Bergmann, Mm, Boeing, H, Li, K, Kaaks, R, Khaw, Kt, Wareham, Nj, Crowe, Fl, Key, Tj, Naska, A, Trichopoulou, A, Trichopoulos, D, Leenders, M, Peeters, Ph, Engeset, D, Parr, Cl, Skeie, G, Jakszyn, P, S?nchez, Mj, Huerta, Jm, Redondo, Ml, Barricarte, A, Amiano, P, Drake, I, Sonestedt, E, Hallmans, G, Johansson, I, Fedirko, V, Romieux, I, Ferrari, P, Norat, T, Vergnaud, Ac, Riboli, E, and Linseisen, J.
Subjects: Male, 030309 nutrition & dietetics, Colorectal cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis [Medical Subject Headings], Review, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], 2700 General Medicine, DISEASE, COLORECTAL-CANCER, VDP::Medical disciplines: 700::Health sciences: 800::Nutrition: 811, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Diet, Meat, Mortality, Cohort, Europe, Cardiovascular, Cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys [Medical Subject Headings], 0302 clinical medicine, Neoplasms, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Medicine(all), RISK, CALIBRATION, 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, cardiovascular, Diabetes, Hazard ratio, food and beverages, cohort, General Medicine, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Nutrition Surveys, Neoplasias, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Näringslära, Cardiovascular Diseases, Red meat, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Enfermedades cardiovasculares, Life Sciences & Biomedicine, Geographicals::Geographic Locations::Americas::North America::United States [Medical Subject Headings], CERTIFICATES, Research Article, Cohort study, Technology, Industry, Agriculture::Food and Beverages::Food::Meat [Medical Subject Headings], Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Processed meat, Estudios de cohortes, Check Tags::Male [Medical Subject Headings], 610 Medicine & health, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding Behavior [Medical Subject Headings], VDP::Medisinske Fag: 700::Helsefag: 800::Ernæring: 811, VEGETARIANS, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, cancer, Humans, ddc:610, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Diseases::Cardiovascular Diseases [Medical Subject Headings], Aged, Science & Technology, business.industry, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Feeding Behavior, medicine.disease, mortality, Survival Analysis, United States, Surgery, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, RED MEAT, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Commentary, 21-YEAR FOLLOW-UP, business, Body mass index, Demography
Abstract: Background Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. Results As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. Conclusions The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.
Published: 2013

67. Development and Validation of a Risk Score Predicting Substantial Weight Gain over 5 Years in Middle-Aged European Men and Women

Author: Philippos Orfanos, Lefkos T. Middleton, Vittorio Krogh, Kuanrong Li, J. Ramón Quirós, Sven Knüppel, Birgit Teucher, Eva Ardanaz, Heiner Boeing, Anne M. May, Laureen Dartois, Guy Fagherazzi, Domenico Palli, Peter Wallström, Bo Hedblad, Jytte Halkjær, Rosario Tumino, Annika Steffen, José María Huerta, María José Sánchez, Amalia Mattiello, Nicholas J. Wareham, Kim Overvad, H. Bas Bueno-de-Mesquita, Kay-Tee Khaw, Daphne L. van der A, Antonia Trichopoulou, Miren Dorronsoro, Anne Tjønneland, Paolo Vineis, Thorkild I. A. Sørensen, Dimitrios Trichopoulos, Noémie Travier, Petra H.M. Peeters, Francesca L. Crowe, [Steffen,A, Knüppel,S, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Sørensen,TIA] Instiute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals – Part of Copenhagen University Hospital, The Capital Region, Denmark. [Travier,N] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain. [Sánchez,MJ] Andalusian School of Public Health, Granada, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Sánchez,MJ, Huerta,JM, Ardanaz,E] CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Ardanaz,E] Navarre Public Health Institute, Pamplona, Spain. [Dorronsoro,M] Basque Regional Health Department and Ciberesp – Biodonostia, San Sebastian, Spain. [Teucher,B, Li,K] Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. [Bueno-de-Mesquita,HB, A,D] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Mattiello,A] Dipartimento di Medicina Clinica e Chirurgia, Frederico II University, Naples, Italy. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, ‘‘Civile – M.P.Arezzo’’ Hospital, Ragusa, Italy. [Krogh,V] Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Vineis,P] HuGeF Foundation Torino, Italy. [Trichopoulou,A, Orfanos,P, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Orfanos,P] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. [Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Hedblad,B] Department of Clinical Sciences in Malmö, Clinical Research Centre, Skane University Hospital, Malmö, Sweden. [Wallström,P] Nutrition Epidemiology Research Group, Department of Clinical Sciences, Lund University, Malmö, Sweden. [Overvad,K] Section of Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Halkjær,J, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Fagherazzi,G, Dartois,L] Inserm, Centre for Research in Epidemiology and Population Health, Institut Gustave Roussy, Villejuif, France. Paris South University, Villejuif, France. [Crowe,F] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom. [Khaw,K] Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom. [Wareham,N] Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. [Vineis,P, Middleton,L] School of Public Health, Imperial College, London, United Kingdom. [May,AM, Peeters,PHM] Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands. [Peeters,PHM] Department of Epidemiology and Public Health, Imperial College London, London, United Kingdom., This publication arises from a collaboration of two EU projects, the Diet, Obesity and Genes (DiOGenes) project and the Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of Home and Obesity (PANACEA) project. DiOGenes is a pan-European study within the EU Sixth Framework Programme for Research and Technological Development (2005-2009) (FOOD-CT-2005-513946, http://www.diogenes.eu.org). PANACEA received funding from the EU in the framework of the Public Health Programme (project 2005328). This work was further supported by the European Commission: Public Health and Consumer Protection Directorate 1993–2004, the Research Directorate-General 2005, the Ligue contre le Cancer, the Societe´ 3M, the Mutuelle Ge´ne´ rale de l’Education Nationale, and the Institut National de la Sante´ et de la Recherche Me´ dicale, German Cancer Aid, the German Cancer Research Center, and the Federal Ministry of Education and Research (Germany), the Danish Cancer Society (Denmark), Health Research Fund (FIS) of the Spanish Ministry of Health RTICC ’Red Tema´tica de Investigacio´n Cooperativa en Ca´ncer (grant number C03/10, R06/0020), the participating regional governments and institutions of Spain, Cancer Research United Kingdom, the Medical Research Council, the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency, and the Wellcome Trust (United Kingdom), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, the Dutch Zorg Onderzoek Nederland, and the World Cancer Research Fund (Netherlands), and the Swedish Cancer Society, the Swedish Scientific Council, and the Regional Government of Skane. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Subjects: Male, Gerontology, Research Validity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Proportional Hazards Models [Medical Subject Headings], Non-Clinical Medicine, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Body Weight Changes::Weight Gain [Medical Subject Headings], Epidemiology, lcsh:Medicine, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Weight Gain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Mediana Edad, 0302 clinical medicine, Risk Factors, Positive predicative value, Aumento de Peso, Cardiac and Cardiovascular Systems, Prospective Studies, 030212 general & internal medicine, Masculino, lcsh:Science, Factores de Riesgo, education.field_of_study, Multidisciplinary, Framingham Risk Score, Nutrition and Dietetics, Adulto, Femenino, Geographicals::Geographic Locations::Europe [Medical Subject Headings], Epidemiology of Aging, Estudios Prospectivos, Middle Aged, Research Assessment, Humanos, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Medicine, Female, Public Health, medicine.symptom, Europa, Research Article, Adult, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Clinical Research Design, Science Policy, Anciano, Population, Check Tags::Male [Medical Subject Headings], 030209 endocrinology & metabolism, External validity, 03 medical and health sciences, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Humans, Obesity, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Statistical Methods, education, Aged, Proportional Hazards Models, Nutrition, Health Care Policy, Receiver operating characteristic, business.industry, Proportional hazards model, lcsh:R, Health Risk Analysis, Check Tags::Female [Medical Subject Headings], lcsh:Q, Modelos de Riesgos Proporcionales, business, Weight gain, Demography
Abstract: Journal Article; Research Support, Non-U.S. Gov't; BACKGROUND Identifying individuals at high risk of excess weight gain may help targeting prevention efforts at those at risk of various metabolic diseases associated with weight gain. Our aim was to develop a risk score to identify these individuals and validate it in an external population. METHODS We used lifestyle and nutritional data from 53°758 individuals followed for a median of 5.4 years from six centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) to develop a risk score to predict substantial weight gain (SWG) for the next 5 years (derivation sample). Assuming linear weight gain, SWG was defined as gaining ≥ 10% of baseline weight during follow-up. Proportional hazards models were used to identify significant predictors of SWG separately by EPIC center. Regression coefficients of predictors were pooled using random-effects meta-analysis. Pooled coefficients were used to assign weights to each predictor. The risk score was calculated as a linear combination of the predictors. External validity of the score was evaluated in nine other centers of the EPIC study (validation sample). RESULTS Our final model included age, sex, baseline weight, level of education, baseline smoking, sports activity, alcohol use, and intake of six food groups. The model's discriminatory ability measured by the area under a receiver operating characteristic curve was 0.64 (95% CI = 0.63-0.65) in the derivation sample and 0.57 (95% CI = 0.56-0.58) in the validation sample, with variation between centers. Positive and negative predictive values for the optimal cut-off value of ≥ 200 points were 9% and 96%, respectively. CONCLUSION The present risk score confidently excluded a large proportion of individuals from being at any appreciable risk to develop SWG within the next 5 years. Future studies, however, may attempt to further refine the positive prediction of the score. Yes
Published: 2013

68. Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection

Author: Asta Försti, Salvador Oyonarte, Carmen Belén Lupiañez, Lourdes Vazquez, Manuel Jurado, Juan Sainz, Juana Segura-Catena, Kari Hemminki, Rafael Rios, [Sainz,J, Lupiáñez,CB, Segura-Catena,J, Ríos,R, Jurado,M] Genomic Oncology Area, Genyo (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain. [Sainz,J, Hemminki,K, Försti, A] Molecular Genetic Epidemiology Department, German Cancer Research Center, Heidelberg, Germany. [Sainz,J, Jurado,M] Haematology Department, University Hospital Virgen de las Nieves, Granada,Spain. [Vazquez,L] Hematology Department, University Hospital of Salamanca, Salamanca, Spain. [Oyonarte,S] Blood Transfusion Regional Centre and Sectorial Tissue Bank, Granada, Spain. [Hemminki,K, Försti,A] Center for Primary Health Care Research, Clinical Research Center, Malmö, Sweden., and This study was supported by grants P08-CVI-4116 from Consejeríaa de Salud de la Junta de Andalucia (Sevilla, Spain) and PI081051 from Fondo de Investigaciones Sanitarias (Madrid, Spain).
Subjects: Male, Epidemiology, Enfermedades Pulmonares Fúngicas, Diseases::Bacterial Infections and Mycoses::Mycoses::Hyalohyphomycosis::Aspergillosis [Medical Subject Headings], lcsh:Medicine, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Aspergillosis, Polymerase Chain Reaction, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mannans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Membrane Glycoproteins::Cell Adhesion Molecules [Medical Subject Headings], Genotype, Molecular Cell Biology, Odds Ratio, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], lcsh:Science, Genetics, Multidisciplinary, Lectinas Tipo C, Fungal genetics, Fungal Diseases, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, Organisms::Eukaryota::Fungi::Mitosporic Fungi::Aspergillus::Aspergillus fumigatus [Medical Subject Headings], Infectious Diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoenzyme Techniques::Enzyme-Linked Immunosorbent Assay [Medical Subject Headings], Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings], Medicine, Female, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface [Medical Subject Headings], Research Article, Adult, Risk, Adolescent, Phenomena and Processes::Mathematical Concepts::Probability::Risk [Medical Subject Headings], Receptores de Superficie Celular, Polimorfismo Genético, Diseases::Bacterial Infections and Mycoses::Mycoses::Lung Diseases, Fungal [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Single-nucleotide polymorphism, Enzyme-Linked Immunosorbent Assay, Receptors, Cell Surface, Biology, Polymorphism, Single Nucleotide, Molecular Genetics, Chemicals and Drugs::Carbohydrates::Polysaccharides::Mannans [Medical Subject Headings], Genetic variation, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Humans, Lectins, C-Type, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Allele, Genetic association, Aged, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Polymorphism, Genetic, Lung Diseases, Fungal, Aspergillus fumigatus, lcsh:R, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Lectins::Lectins, C-Type [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction [Medical Subject Headings], Galactose, Odds ratio, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings], medicine.disease, Ensayo de Inmunoadsorción Enzimática, Mananos, Aspergilosis, Check Tags::Female [Medical Subject Headings], Immunology, Reacción en Cadena de la Polimerasa, Moléculas de Adhesión Celular, lcsh:Q, Polimorfismo de Nucleótido Simple, Cell Adhesion Molecules, Population Genetics
Abstract: Journal Article; Research Support, Non-U.S. Gov't; The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1(rs3901533 T/T) and Dectin-1(rs7309123 G/G) genotypes and DC-SIGN(rs4804800 G), DC-SIGN(rs11465384 T), DC-SIGN(7248637 A) and DC-SIGN(7252229 C) alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37-22.77; OR = 4.91 95%CI 1.52-15.89; OR = 2.75 95%CI 1.27-5.95; OR = 2.70 95%CI 1.24-5.90; OR = 2.39 95%CI 1.09-5.22 and OR = 2.05 95%CI 1.00-4.22, respectively). There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1(rs3901533_T) allele and Dectin-1(rs7309123_G/G) genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1(rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk-adapted prophylaxis. Yes
Published: 2012
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69. Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

Author: Karen Balassiano, Jean-Yves Scoazec, Pierre Hainaut, Petra H.M. Peeters, Federico Canzian, Göran Hallmans, Sara Grioni, Domenico Palli, Bakary S. Sylla, Karina Meidtner, Marí a.José Sánchez, Carmen Navarro, Antonia Trichopoulou, J. Ramón Quirós, Ruth C. Travis, Kim Overvad, Roy Ehrnström, Eva Ardanaz, Eiliv Lund, Carlos A. González, Salvatore Panico, Pagona Laglou, H. Bas Bueno-de-Mesquita, G. Johan A. Offerhaus, Zdenko Herceg, Sheila Coelho Soares Lima, Mazda Jenab, Naomi E. Allen, Kay-Tee Khaw, Rudolf Kaaks, Sara Regnér, Anne Tjønneland, Roger Stenling, Françoise Clavel-Chapelon, Elio Riboli, Heiner Boeing, Núria Sala, M. E. Numans, Marie-Christine Boutron-Ruault, Miren Dorronsoro, Rosario Tumino, Paolo Vineis, Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Department of Cardiology, Aalborg Hospital-Aarhus University Hospital, Danish Cancer Society, Institute of Cancer Epidemiology, 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)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Nutrition, hormones et cancer: épidémiologie et prévention ( E3N ), Epidémiologie, sciences sociales, santé publique ( IFR 69 ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Cancer Epidemiology, German Cancer Research Center, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbrücke, Department of Epidemiology, German Institute of Human Nutrition, Department of Hygiene, Epidemiology and Medical Statistics, Centre for Environment and Health, Imperial College London-School of public health, Human Genetics Foundation ( HuGeF ), Università degli studi di Torino ( UNITO ), Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II-Medical School, Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Epidemiology, Cancer Registry, Azienda Ospedaliera 'Civile M.P.Arezzo', Institute of Community Medicine, University of Tromsø ( UiT ), National Institute for Public Health and the Environment [Bilthoven] ( RIVM ), Julius Centre for Health Sciences and Primary Care, University Medical Center, Julius Center for Health Sciences and Primary Care, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública ( CIBERESP ), Los Centros de Investigación Biomédica en Red (CIBER), Granada Cancer Registry, Andalusian School of Public Health, CIBERESP, CIBER Epidemiologia y Salud Pública, Epidemiology Department, Murcia Health Council, Navarra Public Health Institute, Leyre 15, Epidemiology and Health Information, Public Health Department of Gipuzkoa, Department of Public Health and Clinical Medicine/Nutritional Research, University of Umeå, Cancer Epidemiology Unit, University of Oxford [Oxford]-Cancer Epidemiology Unit, School of Clinical Medicine, University of Cambridge [UK] ( CAM ), Department of Epidemiology and Public Health, Imperial College London, International Agency for Cancer Research ( IACR ), International Agency for Cancer Research, Centre de Recherche en Cancérologie de Lyon ( 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 ), General practice, EMGO - Mental health, Aarhus University Hospital, 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), Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Human Genetics Foundation (HuGeF), Università degli studi di Torino = University of Turin (UNITO), Civile - M.P.Arezzo Hospital, University of Tromsø (UiT), National Institute for Public Health and the Environment [Bilthoven] (RIVM), VU University Medical Center [Amsterdam], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Andalusian School of Public Health [Granada], Umeå University, University of Cambridge [UK] (CAM), International Agency for Cancer Research (IACR), 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), 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), and Università degli studi di Torino (UNITO)
Subjects: MESH: Neoplasm Proteins, Male, Cancer Research, MESH : Aged, MESH : Prospective Studies, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: DNA Methylation, 0302 clinical medicine, MESH : Stomach Neoplasms, MESH : Female, Prospective Studies, MESH: Aged, Genetics, 0303 health sciences, Molecular Epidemiology, MESH: Middle Aged, MESH: Genetic Predisposition to Disease, MESH: Stomach Neoplasms, Methylation, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Neoplasm Proteins, Europe, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Female, MESH : Male, MESH : Europe, MESH : Molecular Epidemiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MLH1, 03 medical and health sciences, MESH : Neoplasm Proteins, p14arf, Stomach Neoplasms, medicine, MESH: Molecular Epidemiology, Humans, Genetic Predisposition to Disease, MESH : Middle Aged, Epigenetics, Gene, 030304 developmental biology, Aged, MESH: Humans, MESH : Humans, Cancer, DNA Methylation, medicine.disease, MESH: Prospective Studies, MESH: Male, MESH : Genetic Predisposition to Disease, MESH: Europe, MESH: Female, MESH : DNA Methylation
Abstract: Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples. A panel of 10 cancer-associated genes (CHRNA3, DOK1, MGMT, RASSF1A, p14ARF, CDH1, MLH1, ALDH2, GNMT and MTHFR) and LINE-1 repetitive elements were included in the analysis and their association with clinicopathological characteristics (sex, age at diagnosis, anatomical sub-site, histological sub-type) was examined. Three out of the 10 genes analyzed exhibited a marked hypermethylation, whereas two genes (ALDH2 and MTHFR) showed significant hypomethylation, in gastric tumors. Among differentially methylated genes, we identified new genes (CHRNA3 and DOK1) as targets of aberrant hypermethylation in GC, suggesting that epigenetic deregulation of these genes and their corresponding cellular pathways may promote the development and progression of GC. We also found that global demethylation of tumor cell genomes occurs in GC, consistent with the notion that abnormal hypermethylation of specific genes occurs concomitantly with genome-wide hypomethylation. Age and gender had no significant influence on methylation states, but an association was observed between LINE-1 and MLH1 methylation levels with histological sub-type and anatomical sub-site. This study identifies aberrant methylation patters in specific genes in GC thus providing information that could be exploited as novel biomarkers in clinics and molecular epidemiology of GC. © 2011 Elsevier Ireland Ltd.
Published: 2011

70. Infection with hepatitis B and C viruses and risk of lymphoid malignancies in theEuropean Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Anja Olsen, Signe Borgquist, Rosario Tumino, Carlotta Sacerdote, Pagona Lagiou, Elio Riboli, Kim Overvad, Sara Regnér, Christina Bamia, Laudina Rodríguez, Kay-Tee Khaw, Bas Bueno-de-Mesquita, Paolo Vineis, Carmen Navarro, Nikolaus Becker, Manuela M. Bergmann, Anne Tjønneland, María José Sánchez, Nicholas J. Wareham, Rudolf Kaaks, Salvatore Panico, Pascale Berthillon, Roel Vermeulen, Ruth C. Travis, Mauro Lise, Beatrice Melin, Domenico Palli, Shu Chun Chuang, Göran Hallmans, Sabina Rinaldi, Alexandra Nieters, Leila Luján Barroso, Antonia Trichopoulou, Silvia Franceschi, Christian Trepo, Pierre Hainaut, Miren Dorronsoro, Heiner Boeing, Sabina Sieri, Aurelio Barricarte, Petra H.M. Peeters, Franceschi, S, Lise, M, Trépo, C, Berthillon, P, Chuang, Sc, Nieters, A, Travis, Rc, Vermeulen, R, Overvad, K, Tjønneland, A, Olsen, A, Bergmann, Mm, Boeing, H, Kaaks, R, Becker, N, Trichopoulou, A, Lagiou, P, Bamia, C, Palli, D, Sieri, S, Panico, Salvatore, Tumino, R, Sacerdote, C, Bueno de Mesquita, B, Peeters, Ph, Rodríguez, L, Barroso, Ll, Dorronsoro, M, Sánchez, Mj, Navarro, C, Barricarte, A, Regnér, S, Borgquist, S, Melin, B, Hallmans, G, Khaw, Kt, Wareham, N, Rinaldi, S, Hainaut, P, Riboli, E, Vineis, P., 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), E16, IFR Laennec (IL), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (CRCL), 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)-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), Molecular Epidemiology, Center of Chronic Immunodeficiency, University Medical Center and University of Freiburg, Institute for Medical Biostatistics and Medical Informatics, University Medical Center and University of Freiburg, Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Section of Epidemiology, Aarhus University [Aarhus], Danish Cancer Society Research Center, Cancer Epidemiology Institute, Danish Cancer Society, Epidemiology, Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Hellenic Health Foundation, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene-Epidemiology and Medical Statistics-Athens Medical School, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Cancer Registry, Azienda Ospedaliera 'Civile M.P.Arezzo', CPO Piemonte, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Centre, Julius Centre for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Julius Center for Health Sciences and Primary Care, Public Health and Participation Directorate, Health and Health Care Services Council, Epidemiology and Health Information, Public Health Department of Gipuzkoa, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Granada Cancer Registry, Andalusian School of Public Health [Granada], CIBERESP, CIBER Epidemiologia y Salud Pública, Epidemiology Department, Murcia Health Council, Navarre Public Health Institute, Department of Oncology, Lund University [Lund]-Lund University Hospital, Department of Radiation Sciences and Oncology, Umeå University, Department of Public Health and Clinical Medicine, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Medical Research Council, Addenbrooke's Hospital-Epidemiology Unit, International Agency for Cancer Research (IACR), Sect Mech Carcinogenesis, School of Public Health, Imperial College London, Centre for Environment and Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), Freiburg University Medical Center, Civile - M.P.Arezzo Hospital, and Lund University Hospital-Lund University [Lund]
Subjects: Male, HBsAg, Epidemiology, medicine.disease_cause, Gastroenterology, 0302 clinical medicine, MESH: Lymphoma, Non-Hodgkin, MESH: Risk Factors, Risk Factors, immune system diseases, hemic and lymphatic diseases, Prospective Studies, MESH: Middle Aged, Lymphoma, Non-Hodgkin, virus diseases, Hepatitis C, Hepatitis B, Middle Aged, MESH: Case-Control Studies, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Oncology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, medicine.medical_specialty, Hepatitis C virus, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, medicine, Humans, Risk factor, Hepatitis B virus, MESH: Hepatitis C, MESH: Humans, MESH: Hepatitis B, business.industry, Odds ratio, medicine.disease, digestive system diseases, MESH: Male, MESH: Prospective Studies, Case-Control Studies, Immunology, MESH: Europe, business, MESH: Female
Abstract: Background: Case–control studies suggested a moderate, but consistent, association of hepatitis C virus (HCV) infection with lymphoid tissue malignancies, especially non–Hodgkin lymphoma (NHL). More limited data suggested that hepatitis B virus (HBV) infection might also be associated with NHL. However, prospective studies on the topic are few. Methods: A nested case–control study was conducted in eight countries participating in the EPIC prospective study. Seven hundred thirty-nine incident cases of NHL, 238 multiple myeloma (MM), and 46 Hodgkin lymphoma (HL) were matched with 2,028 controls. Seropositivity to anti-HCV, anti-HBc, and HBsAg was evaluated and conditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) for NHL, MM, or HL, and their combination. Results: Anti-HCV seropositivity among controls in different countries ranged from 0% to 5.3%; HBsAg from 0% to 2.7%; and anti-HBc from 1.9% to 45.9%. Similar nonsignificant associations were found with seropositivity to HBsAg for NHL (OR = 1.78; 95% CI: 0.78–4.04), MM (OR = 4.00; 95% CI: 1.00–16.0), and HL (OR = 2.00; 95% CI: 0.13–32.0). The association between HBsAg and the combination of NHL, MM, and HL (OR = 2.21; 95% CI: 1.12–4.33) was similar for cancer diagnosed less than 3 and 3 or more years after blood collection. No significant association was found between anti-HCV and NHL, MM, or HL risk, but the corresponding CIs were very broad. Conclusions: Chronic HBV infection may increase the risk of lymphoid malignancies among healthy European volunteers. Impact: Treatment directed at control of HBV infection should be evaluated in HBsAg-seropositive patients with lymphoid tissue malignancies. Cancer Epidemiol Biomarkers Prev; 20(1); 208–14. ©2011 AACR.
Published: 2011

71. Industrially Contaminated Sites and Health

Author: Roberto Pasetto, Piedad Martin-Olmedo, Marco Martuzzi, and [Martuzzi, M] European Centre for Environment and Health, World Health Organization, Regional Office for Europe, Bonn, Germany. [Pasetto,R] Unit of Environmental Epidemiology, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy. [Martin-Olmedo, P] Escuela Andaluza de Salud Pública, Granada, Spain.
Subjects: Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants [Medical Subject Headings], medicine.medical_specialty, Article Subject, Residuos Industriales, Health, Toxicology and Mutagenesis, Population, Industrial Waste, Salud Ambiental, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Environmental health, Environmental monitoring, medicine, Humans, media_common.cataloged_instance, European union, education, Environmental planning, Exposure assessment, media_common, Environmental justice, education.field_of_study, ComputingMilieux_THECOMPUTINGPROFESSION, lcsh:Public aspects of medicine, Public health, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Disciplines and Occupations::Health Occupations::Environmental Health [Medical Subject Headings], Contaminantes Ambientales, Chemicals and Drugs::Complex Mixtures::Waste Products::Industrial Waste [Medical Subject Headings], Health equity, Humanos, Editorial, TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES, Environmental Pollutants, Business, Environmental Health, Waste disposal
Abstract: According to data collected by the European Environment Agency, Europe has hundreds of thousands of contaminated sites [1], many of them resulting from earlier industrialization and poor environmental management. Past and present activities can cause dispersion and accumulation of countless contaminants, mainly chemicals, to an extent that might affect human health by compromising air quality, altering soil functions, entering the food chain, and polluting groundwater and surface water. Typically, but not always, these stressors occur in localized areas near the point sources and affect local communities. The assessment of possible health impacts related to sites hosting or having hosted large or intensive production and processing plants (such as chemicals, petrochemicals, manufacturing, waste disposal and treatment, cement, power generation, mining, and metals) is the main focus of this special issue. Such assessments entail considerable challenges, but the scientific literature repeatedly documented these impacts, often substantial. A variety of methods and tools have been developed for the analysis of these studies: the review included in this special issue by M. Pascal et al., for example, describes the available methodologies for assessing the impacts of airborne contaminants around major industrial areas. These and other resources are available and have been applied in numerous investigations, examples of which are also presented in this special issue: L. Pascal et al. report on hospital admissions near a large industrial area in France; O. Breugelmans et al. studied cancer incidence around a steel plant in The Netherlands, using hierarchical Bayesian models; and R. Pirastu et al. applied different epidemiological approaches to study the health profile of residents in the Italian National Priority Contaminated Site in Taranto. All three studies indicate elevated risks for some of the health outcomes considered, in some cases with large excesses. A number of agents and contaminants examined in these studies are well-established risk factors (e.g., asbestos) and in many cases the evidence provided was instrumental to undertake effective remediation. Available assessments indicate that industrially contaminated sites represent an important public health issue for several reasons: the large extent of contamination and ensuing health impacts, documented in many contaminated sites; the coexistence of multiple environmental stressors; the concurrence of several residential and/or occupational exposure pathways; the largely unknown interaction with risk factors from the social environment, such as lifestyle (nutrition, tobacco consumption, alcohol, physical activity, and housing quality); and the markedly uneven distribution of the risks that raises issues of health inequality and environmental justice. However, while the scientific literature on the subject is rich, it is not yet possible to draw a reliable comprehensive picture of the health impacts of contaminated sites, as some questions remain open. Some of these questions are addressed in this special issue. For a start, the heterogeneity of these sites makes a classification difficult; a common legal definition of contaminated site is not available, nor are common criteria to set up inventories. However, commonalities between certain kinds of areas with respect to the possible health effects exist, and an operational definition of contaminated sites has been proposed as follows: Areas hosting or having hosted human activities which have produced or might produce environmental contamination of soil, surface or groundwater, air, food-chain, resulting or being able to result in human health impacts [2]. The most relevant health outcomes to be considered a priori for different types of industrial activities are identified in this special issue, in a paper by R. Pirastu et al. that also presents an approach to describe the health profile of populations living in industrially contaminated sites using routinely collected data. Epidemiological studies in contaminated sites, especially those focusing on residents (rather than workers), are beset by problems of exposure assessments. Exposure misclassification may in fact compromise the ability of these studies to detect health effects and also, though more rarely, generate false positives. Progress has been made, however, notably through biomonitoring [3] and modelling of dispersion and uptake, as described in this special issue in connection to waste incineration. To pursue better quantification of the overall health impact of contaminated sites, more systematic data are needed to improve the assessment of human exposure. In this respect, many initiatives at the European level have been developed, especially with soil as an entry point. In this special issue, P. Panagos et al. describe the work undertaken in the framework of the European Union (EU) Thematic Strategy for Soil Protection, where the European Commission has identified soil contamination as a priority for the collection of policy-relevant data at continental scale. In addition to raising problems with exposure assessment, industrially contaminated sites are often located close to urban areas and/or socially deprived neighbourhoods; this increases the possible extent of the impacts, makes exposure patterns more complex, and is involved in interactions with other health determinants. Because often the rationale behind these studies is to inform policy decisions, such as remediation, reconversion, or industrial development, there is a need, ideally, to consider all the health stressors occurring in a contaminated site in their entirety, rather than breaking down the question to independent analyses focussing on single contaminants. Such an aspiration to holistic assessments makes the above challenges particularly demanding and should be considered in order to set a research agenda in this domain. Current efforts include WHO-led expert consultations [2]. Taking stock from important national initiatives and current research in epidemiology, exposure assessment, toxicology, environmental monitoring and modelling, human biomonitoring, risk perception, and other disciplines, consensus has emerged on the urgency of the problem and on possible ways forward and goals for international collaborative work, which include producing guidelines on (a) strategies for studying environment and health in contaminated sites and (b) communication strategies; developing resources, materials, and training modules on (a) approaches and methods to be applied in different sites and contexts and (b) communication strategies; strengthening the methodology on exposure assessment, in particular, on biomonitoring and through the food-chain; implementing health assessments that include detailed analyses of population subgroups, in particular, children; planning a system to collect data and produce comparative analyses of the health impact of different sources of contamination within and among different countries, allowing for the inclusion of socioeconomic factors. In conclusion, on the basis of the accumulating evidence on the relevant health impacts (including the contributions contained in this special issue), the need for consistent policies on remediation, and the compelling dimension of the underlying health inequalities, the issue of contaminated sites and health can be considered of priority in the environment and health domain. Existing resources should be further developed and deployed to tackle this important question. Marco Martuzzi Roberto Pasetto Piedad Martin-Olmedo
Published: 2014

72. Behaviour of the pandemic H1N1 influenza virus in Andalusia, Spain, at the onset of the 2009-10 season

Author: L Puell Gómez, M. Pérez Ruiz, A Daponte, JC Carmona, J.C. Fernández Merino, V Gallardo García, J M Navarro Marí, G Andérica, J Guillén Enriquez, E Pérez Morilla, I Mateos, E. Durán Plá, J M Mayoral Cortés, [Mayoral Cortes,JM, Puell Gómez,L, Pérez Morilla,E, Gallardo García,V, Duran Pla,E, Fernandez Merino,JC, Guillén Enriquez,J, Carmona,JC, Anderica,G, Mateos,I] Epidemiology Department, Regional Ministry of Health, Andalusian Regional Government, Spain. [Navarro Marí,JM, and Pérez Ruiz,M] Influenza Reference Laboratory, Virgen de las Nieves Hospital, Granada, Spain. [Daponte,A] Public Health and Health Protection Area, Andalusian Public Health School, Granada, Spain.
Subjects: medicine.medical_specialty, Estaciones, Epidemiology, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Assessment [Medical Subject Headings], Health Care::Environment and Public Health::Public Health::Disease Outbreaks [Medical Subject Headings], España, Check Tags::Male [Medical Subject Headings], Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Causality::Risk Factors [Medical Subject Headings], medicine.disease_cause, Virus, Health Care::Environment and Public Health::Environment::Meteorological Concepts::Atmosphere::Climate::Seasons [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Organisms::Viruses::RNA Viruses::Orthomyxoviridae::Influenzavirus A::Influenza A virus::Influenza A Virus, H1N1 Subtype [Medical Subject Headings], Virology, Pandemic, Influenza A virus, medicine, Subtipo H1N1 del Virus de la Influenza A, Gripe Humana, Factores de Riesgo, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, Incidence (epidemiology), Public health, Brotes de Enfermedades, H1N1 influenza, Public Health, Environmental and Occupational Health, virus diseases, Andalucía, Health Care::Environment and Public Health::Public Health::Public Health Practice::Population Surveillance [Medical Subject Headings], Vigilancia de la Población, Check Tags::Female [Medical Subject Headings], Viral disease, business, Diseases::Virus Diseases::RNA Virus Infections::Orthomyxoviridae Infections::Influenza, Human [Medical Subject Headings], Medición de Riesgo, Health Care::Environment and Public Health::Public Health::Epidemiologic Measurements::Demography::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Demography
Abstract: Journal Article; In Andalusia, Spain, the pandemic influenza A(H1N1)v virus has spread throughout the community, being the dominant influenza strain in the season so far. The current objective of the Andalusia Health Service is focussed on the mitigation of the health and social impact by appropriate care of the patients at home or in health centres. The 2009-10 seasonal influenza epidemic started early compared with to previous seasons. This article analyses the influenza A(H1N1)v situation in Andalusia until the week 39/2009. Yes
Published: 2009

73. Obstetric complications as a risk factor for first psychotic episodes in childhood and adolescence

Author: Miguel Moreno-Iniguez, Mara Parellada, Soraya Otero, Dolores Vigil, Josefina Castro-Fornieles, Felipe Ortuño, Celso Arango, A. Aldama, Ana González-Pinto, Dolores Moreno, Inmaculada Baeza, Montserrat Graell, Dept. of Psychiatry, Adolescent Unit, Hospital General Universitario Gregorio Marañón, Epidemiology Department, Dept. of Child and Adolescent Psychiatry and Psychology, Institut Clinic of Neurosciences IDIBAPS (Institut d'Investigacions Biomèdiques August Pi Sunyer), Hospital Clínic Universitari of Barcelona, Dept. of Psychiatry and Medical Psychology, University Clinic, College of Physicians, University of Navarra, Stanley Institute International Mood-Disorders Research Center 03-RC-003, Hospital Santiago Apóstol, Child and Adolescent Mental Health Unit, Dept. of Psychiatry and Psychology, Hospital Universitario Marqués de Valdecilla [Santander], Section of Child and Adolescent Psychiatry and Psychology, and Hospital Infantil Universitario Niño Jesús
Subjects: Male, early psychosis, Pediatrics, medicine.medical_specialty, Adolescent, first onset, case-control, OCS, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Psychiatric history, ddc:150, Pregnancy, Risk Factors, Developmental and Educational Psychology, medicine, Child and adolescent psychiatry, Humans, Psychology, ddc:610, Medicine, Social Medicine, Risk factor, Child, First episode, Medizin und Gesundheit, business.industry, Psychological Disorders, Mental Health Treatment and Prevention, Case-control study, General Medicine, Odds ratio, medicine.disease, Obstetric Labor Complications, 030227 psychiatry, 3. Good health, Medizin, Sozialmedizin, Psychiatry and Mental health, Psychotic Disorders, Socioeconomic Factors, Psychologie, psychische Störungen, Behandlung und Prävention, Case-Control Studies, Pediatrics, Perinatology and Child Health, Medicine and health, Female, business, 030217 neurology & neurosurgery
Abstract: International audience; There are reports of significant association between obstetric complications (OC) and childhood psychosis. Authors conducted a case-control study of 102 children and adolescents with a first episode psychosis (FEP) and 94 healthy controls (HC), using the obstetric complications scale (OCS) and their medical records, to examine the risk of FPE. Patients were recruited from child and adolescent psychiatry units at six university hospitals and controls from publicly-funded schools of similar characteristics and from the same geographic areas. A logistic regression was performed to quantify the risk of psychosis in childhood and adolescence, based on OC, adjusting for potential confounding factors like socio economic status (SES) and family psychiatric history (FPH). OC appeared more frequently in the records of patients. Significant differences between patients and controls were found in Prenatal OC (15.7% vs. 5.3%
Published: 2009

74. Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the European Prospective Investigation into Cancer and Nutrition (EPIC) prospective study

Author: Carmen Martinez, Petra H.M. Peeters, Merethe Kumle, Paolo Vineis, Armelle Munnia, Seymour Garte, Bas Bueno-de-Mesquita, Emmanuelle Gormally, Ole Raaschou-Nielsen, Antonio Agudo, Giuseppe Matullo, Bengt Järvholm, Françoise Clavel-Chapelon, José Ramón Quirós, Göran Berglund, Marco Peluso, Alison M. Dunning, Rosario Tumino, Alessandro Colombi, Salvatore Panico, Timothy J. Key, Luisa Airoldi, Elio Riboli, S Bingham, Fabrizio Veglia, Rudolf Kaaks, Antonia Trichopoulou, Aurelio Barricarte, Vittorio Krogh, Christian Malaveille, Nicholas E. Day, Kim Overvad, Rodolfo Saracci, Herman Autrup, María José Tormo, Domenico Palli, J. Linseisen, Heiner Boeing, Miren Dorronsoro, Faculteit Medische Wetenschappen/UMCG, Peluso, M, Airoldi, L, Munnia, A, Colombi, A, Veglia, F, Autrup, H, Dunning, A, Garte, S, Gormally, E, Malaveille, C, Matullo, G, Overvad, K, Raaschou Nielsen, O, Clavel Chapelon, F, Linseisen, J, Boeing, H, Trichopoulou, A, Palli, D, Krogh, V, Tumino, R, Panico, Salvatore, Bueno De Mesquita, Bh, Peeters, Ph, Kumle, M, Agudo, A, Martinez, C, Dorronsoro, M, Barricarte, A, Tormo, Mj, Quiros, Jr, Berglund, G, Jarvholm, B, Day, Ne, Key, Tj, Saracci, R, Kaaks, R, Riboli, E, Bingham, S, Vineis, P., [Peluso,M, Munnia, A] Cancer Risk Factor Branch, Analytical and Biomolecular Cytology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy. [Airoldi,L, Colombi,A] Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. [Veglia, F, Matullo,G] ISI Foundation, Turin, Italy. [Autrup,H] Department of Environmental and Occupational Medicine, Aarhus, Denmark. [Dunning, A] Department of Oncology, University of Cambridge, Cambridge, UK. [Garte,S] Genetics Research Institute, Milan, Italy. [Gormally,E, Malaveille,C] International Agency for Research on Cancer, Lyon, France. [Overhad,K] Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Raaschou-Nielsen,O] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Clavel-Chapelon,F] INSERM (Institut National de la Sante´ et de la Recherche Me´dicale), ERI 20, EA 4045, and Institut Gustave Roussy, Villejuif, F-94805, France. [Linseisen,J] Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, German. [Boeing,H] German Institute of Human Nutrition, Potsdam-Rehbu¨cke, Germany. [Trichopoulou,A] Department of Hygiene and Epidemiology, Medical School, University of Athens, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, CSPO-Scientiﬁc Institute of Cancer Prevention Tuscany Region, Florence, Italy. [Krogh,V] Department of Epidemiology, National Cancer Institute, Milan, Italy. [Tumino,R] Cancer Registry, Azienda Ospedaliera ‘Civile MP Arezzo’, Ragusa, Ital. [Panico,S] Dipartimento di Medicina Clinica e Sperimentale, Universita` Federico II, Naples, Italy. [Bueno-De-Mesquita,BH] Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherland. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. [Kumle,M] Institute of Community Medicine, University of Tromso, Tromso, Norway. [Agudo,A] Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain. [Martinez,C] Andalusian School of Public Health, Granada, Spain. [Dorronsoro,M] Department of Public Health of Guipuzkoa, San Sebastian, Spain. [Barricarte,A] Public Health Institute, Navarra, Spain. [Tormo,MJ] Epidemiology Department, Murcia Health Council, Murcia, Spain. Quiros, JR] Direccio´n General de Salud Pu´blica, Consejerı´a de Salud y Servicios Sanitarios Asturias, Oviedo, Spain. [Berglund,G] Malmo¨ Diet and Cancer Study, Lund University, Malmo¨, Sweden. [Jarvholm,G] Department of Nutritional Research, University of Umea˚, Umea˚ , Sweden. [Day,ND, Bingham,S] MRC Dunn Human Nutrition Unit, Cambridge University, UK. [Key,TJ].Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, UK. [Saracci,R] IFC National Research Council, Pisa, Italy. [Kaas,R] Division of Epidemiology, DKFZ Heidelberg, Germany. [Riboli,E] Imperial College London, London, UK. [Vineis,P] University of Turin, Turin, Italy. Department of Epidemiology and Public Health, Imperial College of Science, Technology and Medicine, Norfolk Place, London W2 1PG, UK, This paper was made possible by a grant of the European Community (5th Framework Programme) to P. V. (grant QLK4–CT–1999–00 927) and a grant of the Compagnia di San Paolo to the ISI Foundation. All authors are independent from funders. Mortality data for the Netherlands were obtained from Statistics Netherlands. Also, the work described in the paper was carried out with the financial support of: Europe Against Cancer Program of the European Commission (SANCO), ISCIII, Red de Centros RCESP, C03/09, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Dutch Ministry of Public Health, Welfare and Sports, World Cancer Research Fund, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Ska°ne, Sweden, Norwegian Cancer Society, and Research Council of Norway.
Subjects: Dietary Fiber, Male, Aflatoxin, Erythrocytes, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Hemoglobins [Medical Subject Headings], medicine.medical_treatment, air pollution, RESISTANT STARCH, Medicine (miscellaneous), GUIDELINES, Carcinógenos, Body Mass Index, COLORECTAL-CANCER, Food group, chemistry.chemical_compound, Hemoglobins, Vegetables, Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants::Air Pollutants [Medical Subject Headings], Leukocytes, Aductos de ADN, Nutritional Physiological Phenomena, Food science, Prospective Studies, RISK, DNA adducts, Haemoglobin adducts, Non-smokers, Fibre intake, Air pollution, Publication Characteristics::Study Characteristics::Multicenter Study [Medical Subject Headings], Air Pollutants, Nutrition and Dietetics, Chemistry, Technology, Industry, Agriculture::Food and Beverages::Food::Dietary Fiber [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Noxae::Carcinogens [Medical Subject Headings], COLON-CANCER, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage::DNA Adducts [Medical Subject Headings], Fabaceae, Middle Aged, fibre intake, European Prospective Investigation into Cancer and Nutrition, Europe, Biochemistry, 4-Aminobiphenyl, Colonic Neoplasms, Hemoglobinas, Female, SMOKERS, Alcohol Drinking, BLADDER-CANCER, European Prospective Investigation into Cancer and Nutrition (EPIC), haemoglobin adducts, non-smokers, RATS, POLYCYCLIC AROMATIC-HYDROCARBONS, Ozone, LUNG-CANCER, DNA adduct, medicine, Humans, Contaminantes del aire, ddc:610, Carcinogen, Aged, Estudio multicéntrico, Vitamin E, Fruit, Multivariate Analysis, Fibras en la dieta, Carcinogens, Biomarkers, Food contaminant
Abstract: Udgivelsesdato: 2008-Feb-14 In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse, statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P = 0.02), vitamin E (P = 0.04) and alcohol (P = 0.03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P = 0.03, 0.04, and 0.03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances.
Published: 2008

75. Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study

Author: Carlo Ferrarese, Lorene M. Nelson, Caroline M. Tanner, Brian K. Fiske, George D. Mellick, Richard M. Myers, Beate Ritz, Grazia Annesi, Karin Wirdefeldt, Christine Van Broeckhoven, Karen Marder, Marie Dehem, Stewart A. Factor, Donald S. Higgins, John G. Nutt, Stephen K. Van Den Eeden, Andrea Carmine Belin, Cyrus P. Zabetian, Rejko Krüger, Haydeh Payami, Jennifer S. Montimurro, Georgios M. Hadjigeorgiou, John P. A. Ioannidis, Hideshi Kawakami, Audrey Southwick, Ali Samii, Alexis Elbaz, Richard Mayeux, Thomas A Trikalinos, Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Epidemiology, Department of Health Research and Policy, Stanford University, New York State Department of Health [Albany], Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, The Michael J Fox Foundation for Parkinson's Research, Institute of Neurological Sciences, National Research Council [Italy] (CNR), Neuroscience Department, Karolinska Institutet [Stockholm], Department of Neurology, Emory University [Atlanta, GA], Department of Neuroscience-Section of Neurology, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), School of Medicine, Larissa, University of Thessaly [Volos] (UTH), Parkinson's Disease and Movement Disorder Clinic, Albany Medical College, Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Center of Neurology and Hertie-Institute for Clinical Brain Research, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, The Gertrude H Sergivesky Center, Columbia University College of Physicians and Surgeons, Eskitis Institute for Cell and Molecular Therapies, Griffi th University, Oregon Health and Science University [Portland] (OHSU), Department of Epidemiology, University of California [Los Angeles] (UCLA), University of California-University of California, Parkinson Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, The Parkinson's Institute, The Parkinson's Institute, Sunnyvale, Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Antwerpen, Division of Research, Kaiser Permanente, Department of Medical Epidemiology and Biostatistics (MEB), Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, University of Washington [Seattle], Genoscreen, Genoscreen, Lille, Department of Genetics [Stanford], Stanford Medicine, Stanford University-Stanford University, Theuns, Jessie, Pals, Philippe, Nuytemans, Karen, Pickut, Barbara, Cras, Patrick, De Deyn, Peter Paul, Tzourio, Christophe, University of Ioannina, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), University of California (UC)-University of California (UC), Elbaz, A, Nelson, L, Payami, H, Ioannidis, J, Fiske, B, Annesi, G, Carmine Belin, A, Factor, S, Ferrarese, C, Hadjigeorgiou, G, Higgins, D, Kawakami, H, Krueger, R, Marder, K, Mayeux, R, Mellick, G, Nutt, J, Ritz, B, Samii, A, Tanner, C, van Broeckhoven, C, van den Eeden, S, Wirdefeldt, K, Zabetian, C, Dehem, M, Montimurro, J, Southwick, A, Myers, R, and Trikalinos, T
Subjects: Male, Linkage disequilibrium, Polymorphism, Single Nucleotide/*genetics, Ethnic origin, Linkage Disequilibrium, 0302 clinical medicine, Odds Ratio, Genetics, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, Middle Aged, MESH: Confidence Intervals, 3. Good health, MESH: Linkage Disequilibrium, Meta-analysis, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Meta-Analysis, Single-nucleotide polymorphism, Biology, Article, Parkinson Disease/epidemiology/*genetics, 03 medical and health sciences, Meta-Analysis as Topic, Genetic predisposition, Confidence Intervals, SNP, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030304 developmental biology, Aged, MED/26 - NEUROLOGIA, MESH: Humans, Genetic heterogeneity, International Cooperation, Odds ratio, MESH: Odds Ratio, MESH: Male, MESH: International Cooperation, Genetic Predisposition to Disease, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Parkinson's disease, single-nucleoide polymorphism, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), MESH: Female, 030217 neurology & neurosurgery, MESH: Parkinson Disease
Abstract: International audience; BACKGROUND: A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson's disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain. METHODS: Investigators from three Michael J Fox Foundation for Parkinson's Research-funded genetics consortia-comprising 14 teams-contributed DNA samples from 5526 patients with Parkinson's disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies. FINDINGS: In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0.89 to 1.09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0.95 to 1.08); there was little heterogeneity except for SNP rs7520966. INTERPRETATION: Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson's disease.
Published: 2006

76. Plasma levels of six carotenoids in nine European countries: report from the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Anne Linda Van Kappel, Françloise Clavel-Chapelon, Jean-Paul Steghens, Kim Overvad, Nadia Slimani, Petra H.M. Peeters, Sheila Bingham, H. Bas Bueno-de-Mesquita, Catherine Guibout, Vassiliki Benetou, Ingegerd Johansson, Ailsa A Welch, José Ramón Quirós, Anne Tjønneland, Antonia Trichopoulou, Heiner Boeing, Egidio Celentano, Domenico Palli, Rudolf Kaaks, Wael K. Al-Delaimy, Carmen Navarro, Peter Wallström, Jakob Linseisen, Pietro Ferrari, Timothy J. Key, Elio Riboli, Unit of Nutrition and Cancer, International Agency for Cancer Research (IACR), Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Nutrition Unit, MRC Dunn Human, Laboratory of Plant Physiology and Biophysics, IBLS Plant Sciences, University of Glasgow, Department of Plant Biochemistry, Lund University [Lund], Department of Cardiology and Department of Clinical Epidemiology, Aarhus University Hospital, Department of Clinical Epidemiology, Institute og Cancer Epidemiology, Danish Cancer Society, Institute of Cancer Epidemiology, Radcliffe Infirmary, Cancer Research UK, Cancer Research UK Epidemiology Unit, University of Oxford [Oxford], National Institute for Public Health and the Environment [Bilthoven] (RIVM), Center for Nutrition and Health, National Institute of Public Health and Environment, Julius Centre for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Julius Center for Health Sciences and Primary Care, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Division of Clinical Epidemiology, Deutches Krebsforschungszentrum, Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Epidémiologie des cancers, Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie des cancers : Radiocarcinogénèse et effets iatrogènes des traitements, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departamento de Biología Animal, Universidad de Extremadura (UEX)-Departamento de Biología Animal, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Epidemiology Department, Health Council of Murcia, Public Health and Health Planning Directorate, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Center, University of Athens Medical School [Athens], Department of Hygiene and Epidemiology, Unit of nutritional cancer, IARC-WHO, Nutrition and Hormone Group, Guibout, Catherine, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Aalborg Hospital-Aarhus University Hospital, Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), University of Athens Medical School, Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Universidad de Extremadura - University of Extremadura (UEX)-Departamento de Biología Animal
Subjects: Male, Lutein, 030309 nutrition & dietetics, Medicine (miscellaneous), Body Mass Index, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Reference Values, Epidemiology, Medicine, Nutritional Physiological Phenomena, Prospective Studies, MESH: Cohort Studies, Carotenoid, 2. Zero hunger, chemistry.chemical_classification, 0303 health sciences, MESH: Middle Aged, Nutrition and Dietetics, Smoking, MESH: Reference Values, food and beverages, MESH: Life Style, Middle Aged, MESH: Nutrition Physiology, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Zeaxanthin, Cohort, Female, Seasons, MESH: Smoking, medicine.medical_specialty, Alcohol Drinking, 030209 endocrinology & metabolism, MESH: Body Mass Index, 03 medical and health sciences, MESH: Cross-Sectional Studies, Humans, ddc:610, Life Style, MESH: Humans, business.industry, Public Health, Environmental and Occupational Health, alpha-Carotene, Carotenoids, MESH: Prospective Studies, MESH: Male, Cross-Sectional Studies, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Carotenoids, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Europe, business, MESH: Seasons, MESH: Female, Body mass index, MESH: Alcohol Drinking, Demography
Abstract: Background:In addition to their possible direct biological effects, plasma carotenoids can be used as biochemical markers of fruit and vegetable consumption for identifying diet–disease associations in epidemiological studies. Few studies have compared levels of these carotenoids between countries in Europe.Objective:Our aim was to assess the variability of plasma carotenoid levels within the cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods:Plasma levels of six carotenoids – α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin – were measured cross-sectionally in 3043 study subjects from 16 regions in nine European countries. We investigated the relative influence of gender, season, age, body mass index (BMI), alcohol intake and smoking status on plasma levels of the carotenoids.Results:Mean plasma level of the sum of the six carotenoids varied twofold between regions (1.35μmoll−1for men in Malmö, Sweden vs. 2.79μmoll−1for men in Ragusa/Naples, Italy; 1.61μmoll−1for women in The Netherlands vs. 3.52μmoll−1in Ragusa/Naples, Italy). Mean levels of individual carotenoids varied up to fourfold (α-carotene: 0.06μmoll−1for men in Murcia, Spain vs. 0.25μmoll−1for vegetarian men living in the UK). In multivariate regression analyses, region was the most important predictor of total plasma carotenoid level (partialR2=27.3%), followed by BMI (partialR2=5.2%), gender (partialR2=2.7%) and smoking status (partialR2=2.8%). Females had higher total carotenoid levels than males across Europe.Conclusions:Plasma levels of carotenoids vary substantially between 16 different regions in Italy, Greece, Spain, France, Germany, the UK, Sweden, Denmark and The Netherlands. Compared with region of residence, the other demographic and lifestyle factors and laboratory measurements have limited predictive value for plasma carotenoid levels in Europe.
Published: 2004

77. A combined analysis of the short-term effects of photochemical air pollutants on mortality within the EMECAM project

Author: Federico Arribas, Nuria Aragonés, Aurelio Tobias, Álvaro Cañada, Juan Bellido, Lluís Cirera, Maria Antònia Barceló, Ferran Ballester, Marc Saez, José María Tenías, Ricardo Ocaña, Santiago Pérez-Hoyos, Adolfo Figueiras, The EMECAM group, [Saez,M, Barceló,A] Research Group on Statistics, Applied Economics and Health, GRECS, Department of Economics, University of Girona, Spain. [Ballester,F, Pérez-Hoyos,S, and Tenías,JM] Epidemiology and Statistics Unit, Valencian School for Health Studies (EVES), Spain. [Bellido,J] Epidemiological Service, Regional Health Authority, Castelló, Spain. [Ocaña,R] Andalusian School of Public Health, Granada, Spain. [Figueiras,A] Preventive Medicine, University of Santiago de Compostela, Spain. [Arribas,F] Health, Welfare and Labour Department, Zaragoza, Spain. [Aragonés,N] Public Health Authority, Madrid, Spain. [Tobías,A] Department of Clinical Epidemiology and Public Health, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Cirera,L] Epidemiology Department, Regional Health Council, Murcia, Spain. [Cañada,Á] Public Health Regional Authority, Social Services Council, Oviedo, Spain.
Subjects: Male, Geographicals::Geographic Locations::Cities [Medical Subject Headings], Combinatorial analysis, Health, Toxicology and Mutagenesis, España, Air pollution, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Photochemistry, medicine.disease_cause, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, Contaminants, Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants::Air Pollutants [Medical Subject Headings], Child, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Dióxido de Nitrógeno, Air Pollutants, Named Groups::Persons::Age Groups::Child::Child, Preschool [Medical Subject Headings], Aire -- Contaminació, Oxidantes Fotoquímicos, Environmental exposure, Middle Aged, Random effects model, Health Care::Environment and Public Health::Public Health::Environmental Pollution::Environmental Exposure [Medical Subject Headings], Chemicals and Drugs::Inorganic Chemicals::Gases::Oxygen::Ozone [Medical Subject Headings], Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings], Child, Preschool, Regression Analysis, Female, Named Groups::Persons::Age Groups::Infant [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Oxidants::Oxidants, Photochemical [Medical Subject Headings], Anàlisi combinatòria, Air -- Pollution, Research Article, Adult, Pollutants, Adolescent, Nitrogen Dioxide, Named Groups::Persons::Age Groups::Infant::Infant, Newborn [Medical Subject Headings], Chemicals and Drugs::Inorganic Chemicals::Gases::Nitrogen Oxides::Nitrogen Dioxide [Medical Subject Headings], Risk Assessment, Oxidants, Photochemical, Ozone, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Mortalitat, Humans, Nitrogen dioxide, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Cities, Mortality, Ozono, Named Groups::Persons::Age Groups::Child [Medical Subject Headings], Aged, Pollutant, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Regression Analysis [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Assessment [Medical Subject Headings], Public Health, Environmental and Occupational Health, Infant, Newborn, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality [Medical Subject Headings], Infant, Fixed effects model, Environmental Exposure, Confidence interval, Epidemiologic Studies, Check Tags::Female [Medical Subject Headings], chemistry, Spain, Relative risk, Contaminantes del Aire, Environmental science, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies [Medical Subject Headings]
Abstract: Journal Article; Research Support, Non-U.S. Gov't; In recent years, some epidemiologic studies have attributed adverse effects of air pollutants on health not only to particles and sulfur dioxide but also to photochemical air pollutants (nitrogen dioxide and ozone). The effects are usually small, leading to some inconsistencies in the results of the studies. Furthermore, the different methodologic approaches of the studies used has made it difficult to derive generic conclusions. We provide here a quantitative summary of the short-term effects of photochemical air pollutants on mortality in seven Spanish cities involved in the EMECAM project, using generalized additive models from analyses of single and multiple pollutants. Nitrogen dioxide and ozone data were provided by seven EMECAM cities (Barcelona, Gijón, Huelva, Madrid, Oviedo, Seville, and Valencia). Mortality indicators included daily total mortality from all causes excluding external causes, daily cardiovascular mortality, and daily respiratory mortality. Individual estimates, obtained from city-specific generalized additive Poisson autoregressive models, were combined by means of fixed effects models and, if significant heterogeneity among local estimates was found, also by random effects models. Significant positive associations were found between daily mortality (all causes and cardiovascular) and NO(2), once the rest of air pollutants were taken into account. A 10 microg/m(3) increase in the 24-hr average 1-day NO(2)level was associated with an increase in the daily number of deaths of 0.43% [95% confidence interval (CI), -0.003-0.86%] for all causes excluding external. In the case of significant relationships, relative risks for cause-specific mortality were nearly twice as much as that for total mortality for all the photochemical pollutants. Ozone was independently related only to cardiovascular daily mortality. No independent statistically significant relationship between photochemical air pollutants and respiratory mortality was found. The results in this study suggest that, given the present levels of photochemical pollutants, people living in Spanish cities are exposed to health risks derived from air pollution. Yes
Published: 2002

78. 口腔内プラーク形成に対する卵黄抗体製品Ovalgen DCの効果(最近のトピックス保健衛生学関連)

Author: Itsuo, CHIBA, 北海道医療大学歯学部口腔構造・機能発育学系保健衛生学分野, and Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, Health Sciences University of Hokkaido
Published: 2007

79. Guillain-Barré syndrome following the 2009 pandemic monovalent and seasonal trivalent influenza vaccination campaigns in Spain from 2009 to 2011: outcomes from active surveillance by a neurologist network, and records from a country-wide hospital discharge database

Author: Alcalde Cabero, Enrique, Almazan Isla, Javier, García López, Fernando J., Ara Callizo, José Ramón, Avellanal, Fuencisla, Casasnovas Pons, Carlos, Cemillán, Carlos, Cuadrado, José Ignacio, Duarte, Jacinto, Fernández Pérez, María Dolores, Fernández, Óscar, García Merino, Juan Antonio, García Montero, Rosa, Montero, Dolores, Pardo, Julio, Rodríguez Rivera, Francisco Javier, Ruiz Tovar, María, Pedro Cuesta, Jesús de, Spanish GBS Epidemiology Study Group, Universitat de Barcelona, Spanish GBS Epidemiology Study Group, [Alcalde-Cabero,E, Almazán-Isla,J, García López,FJ, Avellanal,F, Ruiz Tovar,M, and de Pedro-Cuesta,J] National Centre for Epidemiology, CIBERNED, Carlos III Health Institute, Madrid, Spain. [Ara-Callizo,JR] Neurology Department, Miguel Servet University Hospital, Zaragoza, Spain. [Casasnovas,C] Neuromuscular Unit, Neurology Department, Bellvitge University Hospital, Bellvitge. Biomedical Research Institute (Institut d’Investigació Biomèdica de Bellvitge/IDIBELL), L’Hospitalet de Llobregat, Spain. [Cemillán,C] Neurology Department, Severo Ochoa University Hospital, Leganés, Madrid, Spain. [Cuadrado,JI] Epidemiology Department, Regional Ministry of Health, Madrid Autonomous Region, Spain. [Duarte,J] Neurology Department, General Hospital, Segovia, Spain. [Fernández-Pérez,MD] Neurology Department, Virgen de las Nieves University Hospital, Granada, Spain. [Fernández,O] Neurology Department, Carlos Haya University Hospital, Málaga, Spain. [García Merino,JA] Neurology Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain. [García Montero,R] Neurology Department, Virgen de la Salud Hospital, Toledo, Spain. [Montero,D] Spanish Medicines & Medical Devices Agency (Agencia Española de Medicamentos y Productos Sanitarios), Madrid, Spain. [Pardo,J] Neurology Department, University Teaching Hospital Clínico, Santiago de Compostela (Corunna), Spain. [Rodríguez-Rivera,FJ] Neurology Department, La Paz University Hospital, Madrid, Spain.
Subjects: Male, Pediatrics, Hospitales generales, Time Factors, Síndrome de Guillain-Barré, Databases, Factual, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Autoimmune diseases, España, Vacunas contra la influenza, Proyectos piloto, ICD-9-CM, Vacunes, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Influenza A Virus, H1N1 Subtype, Public health surveillance, Estudios prospectivos, Pandemic, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization [Medical Subject Headings], Peripheral nerves, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Vaccines, Guillain-Barre syndrome, Malalties autoimmunitàries, Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospitals::Hospitals, General [Medical Subject Headings], Incidence (epidemiology), Incidence, virus diseases, Síndrome de Miller Fisher, General Medicine, Middle Aged, Guillain-Barré syndrome, Phenomena and Processes::Physical Phenomena::Time::Periodicity::Seasons [Medical Subject Headings], Vaccination, Influenza vaccines, Chemicals and Drugs::Complex Mixtures::Biological Agents::Vaccines::Viral Vaccines::Influenza Vaccines [Medical Subject Headings], Inmunización, Epidemiological Monitoring, Sistema de registros, Female, Disciplines and Occupations::Health Occupations::Medicine::Neurology [Medical Subject Headings], Safety, Incidencia, Research Article, Subtipo H1N1 del virus de la influenza A, Trivalent influenza vaccine, Adult, Information Science::Information Science::Information Services::Documentation::Vocabulary, Controlled::International Classification of Diseases [Medical Subject Headings], medicine.medical_specialty, Phenomena and Processes::Mathematical Concepts::Probability::Risk [Medical Subject Headings], Clinical Neurology, Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebellar Diseases::Miller Fisher Syndrome [Medical Subject Headings], Nervis perifèrics, Estaciones del año, Guillain-Barre Syndrome, Riesgo, Influenzavirus, Clasificación internacional de enfermedades, Grip, Estudios retrospectivos, 03 medical and health sciences, Neuritis, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Organisms::Viruses::RNA Viruses::Orthomyxoviridae::Influenzavirus A::Influenza A virus::Influenza A Virus, H1N1 Subtype [Medical Subject Headings], Gripe Humana, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Humans, Influenza viruses, Neurologists, Diseases::Nervous System Diseases::Neuromuscular Diseases::Peripheral Nervous System Diseases::Neuritis [Medical Subject Headings], Intensive care medicine, Pandemics, Aged, Retrospective Studies, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Pilot Projects [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunotherapy, Active::Vaccination [Medical Subject Headings], business.industry, Vacunación, Retrospective cohort study, medicine.disease, Diseases::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Polyradiculoneuropathy::Guillain-Barre Syndrome [Medical Subject Headings], Influenza, Spain, Influenza A virus H1N1 subtype, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Registries [Medical Subject Headings], Neurology (clinical), Diseases::Virus Diseases::RNA Virus Infections::Orthomyxoviridae Infections::Influenza, Human [Medical Subject Headings], business, 030217 neurology & neurosurgery
Abstract: BACKGROUND: Studies have shown a slight excess risk in Guillain-Barré syndrome (GBS) incidence associated with A(H1N1)pdm09 vaccination campaign and seasonal trivalent influenza vaccine immunisations in 2009-2010. We aimed to assess the incidence of GBS as a potential adverse effect of A(H1N1)pdm09 vaccination. METHODS: A neurologist-led network, active at the neurology departments of ten general hospitals serving an adult population of 4.68 million, conducted GBS surveillance in Spain in 2009-2011. The network, established in 1996, carried out a retrospective and a prospective study to estimate monthly alarm thresholds in GBS incidence and tested them in 1998-1999 in a pilot study. Such incidence thresholds additionally to observation of GBS cases with immunisation antecedent in the 42 days prior to clinical onset were taken as alarm signals for 2009-2011, since November 2009 onwards. For purpose of surveillance, in 2009 we updated both the available centres and the populations served by the network. We also did a retrospective countrywide review of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis from January 2009 to December 2011. RESULTS: Among 141 confirmed of 148 notified cases of GBS or Miller-Fisher syndrome, Brighton 1-2 criteria in 96 %, not a single patient was identified with clinical onset during the 42-day time interval following A(H1N1)pdm09 vaccination. In contrast, seven cases were seen during a similar period after seasonal campaigns. Monthly incidence figures did not, however, exceed the upper 95 % CI limit of expected incidence. A retrospective countrywide review of the registry of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis did not suggest higher admission rates in critical months across the period December 2009-February 2010. CONCLUSIONS: Despite limited power and underlying reporting bias in 2010-2011, an increase in GBS incidence over background GBS, associated with A(H1N1)pdm09 monovalent or trivalent influenza immunisations, appears unlikely Sí

80. Characterization of new users of cilostazol in the UK, Spain, Sweden, and Germany

Author: Castellsagué, Jordi, Perez-Gutthann, Susana, Calingaert, Brian, Bui, Christine, Varas-Lorenzo, Cristina, Arana, Alejandro, Prados-Torres, Alexandra, Poblador-Plou, Beatriz, Gonzalez-Rubio, Francisca, Giner-Soriano, Maria, Roso-Llorach, Albert, Linder, Marie, Citarella, Anna, Scholle, Oliver, Blenk, Tilo, Garbe, Edeltraut, (Castellsague J, Perez-Gutthann S, Varas-Lorenzo C, Arana A) Department of Epidemiology, RTI Health Solutions, Barcelona, Spain, (Calingaert B, Bui C) Department of Epidemiology, RTI Health Solutions, Durham, NC, USA., (Prados-Torres A, Poblador-Plou B, Gonzalez-Rubio F) EpiChron Research Group on Chronic Diseases, IIS Aragón, Aragon Health Sciences Institute (IACS), REDISSEC, Zaragoza, Spain., (Giner-Soriano M, Roso-Llorach A) Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain., (Linder M, Citarella) Centre for Pharmacoepidemiology, Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden., (Scholle O, Blenk T, Garbe E) Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology-BIPS, Bremen, Germany, and IDIAP Jordi Gol
Subjects: pharmacoepidemiology, database study, cilostazol, drug utilization study, intermittent claudication, peripheral artery disease, Farmacologia, Natural Science Disciplines::Biological Science Disciplines::Pharmacology::Pharmacoepidemiology [DISCIPLINES AND OCCUPATIONS], enfermedades cardiovasculares::enfermedades vasculares::arteriopatías oclusivas::arteriosclerosis::aterosclerosis::arteriopatía periférica [ENFERMEDADES], Claudicació intermitent, Medicaments - Efectes secundaris, enfermedades cardiovasculares::enfermedades vasculares::arteriopatías oclusivas::arteriosclerosis::claudicación intermitente [ENFERMEDADES], Cardiovascular Diseases::Vascular Diseases::Arterial Occlusive Diseases::Arteriosclerosis::Intermittent Claudication [DISEASES], Cardiovascular Diseases::Vascular Diseases::Arterial Occlusive Diseases::Arteriosclerosis::Atherosclerosis::Peripheral Arterial Disease [DISEASES], disciplinas de las ciencias naturales::disciplinas de las ciencias biológicas::farmacología::farmacoepidemiología [DISCIPLINAS Y OCUPACIONES]
Abstract: Cilostazol; Intermittent claudication; Drug utilization study; Database study; Pharmacoepidemiology; Peripheral artery disease Purpose To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency. Methods New users of cilostazol were identified in populations enrolled in five European health automated databases in the UK (The Health Improvement Network [THIN]), Spain (EpiChron cohort and Information System for the Improvement of Research in Primary Care [SIDIAP]), Sweden (National Registers), and Germany (German Pharmacoepidemiological Research Database [GePaRD]) between 2002 and 2012. New users were characterized according to t he prevalence of cardiovascular disease and other comorbidities, concurrent use of interacting medications, new contraindications, duration of use, and potential off-label prescribing. Results We identified 22 593 new users of cilostazol. The median age was between 68.0 (THIN) and 73.7 (Sweden) years. More than 78% of users had concomitant cardiovascular disease, and between 78.8% (GePaRD) and 91.6% (THIN) were treated with interacting medications. Prevalence of new cardiovascular contraindications ranged from 1.5% (THIN) to 11.6% (GePaRD), and concurrent use of two or more antiplatelet drugs ranged from 6.3% (SIDIAP) to 13.5% (EpiChron cohort). Between 39.4% (Sweden) and 52.9% (THIN) of users discontinued cilostazol in the first 3 months. Between 41.0% (SIDIAP) and 93.4% (THIN) were considered to have received cilostazol according to the European Medicines Agency labeling. Conclusions In this collaborative European study,most cilostazol users were elderly patients with a high prevalence of cardiovascular diseases and other comorbidity and concurrent use of interacting drugs, indicating that this is a vulnerable population at high risk of complications, especially cardiovascular events.

81. Dynamics of multisystem inflammatory syndrome in children associated to COVID-19 in Chile: Epidemiologic trends during pandemic, before and after children vaccination.

Author: Villena R, Izquierdo G, Wilhelm J, García C, Acuña M, Riquelme P, Alvarado S, and Torres JP
Subjects: Humans, Chile epidemiology, Child, Male, Female, Child, Preschool, Infant, Adolescent, Infant, Newborn, Incidence, Pandemics prevention & control, COVID-19 epidemiology, COVID-19 prevention & control, COVID-19 complications, COVID-19 Vaccines administration & dosage, Systemic Inflammatory Response Syndrome epidemiology, SARS-CoV-2 immunology, Vaccination statistics & numerical data
Abstract: Background: Multisystem inflammatory syndrome associated to Covid-19 (MIS-C) is one of the most severe outcomes of SARS-CoV-2 in children. Covid-19 vaccines were successfully implemented in Chile for the pediatric population since 2021, using both mRNA and inactivated platforms. Effectiveness against MIS-C has been reported for mRNA vaccines. The aim of this study was to describe the epidemiologic trend of MIS-C in Chile during Covid-19 pandemic, both before and after the availability of vaccination for children., Materials and Methods: Analytic study of MIS-C cases from April 2020 to December 2022. Epidemiological data, SARS-CoV-2 variants and vaccination uptake information were obtained from the Epidemiology Department-Ministry of Health, Institute of Public Health and the National Immunization Program, respectively., Results: 496 cases of MIS-C were reported, 58 % males. Median age was 5 years and most frequent age-cohorts were 6-11 and 0-2 years old with a 33 % each. After the introduction of the Covid-19 vaccine, most cases occurred in children aged 0-2 years. Incidence rates were 3.8, 5.4 and 1.7 per 100,000 inhabitants in 2020, 2021 and 2022, respectively. 97 % of cases (481) occurred in unvaccinated subjects. On those previously vaccinated (15), all but one case occurred in children receiving the inactivated vaccine. No association among circulating variants and incidence was observed. Incidence rate reduction (IRR) comparison between 2020 and 2021-2022 periods was 0.72 (CI 95 % 0.65-0.81, p < 0.05) overall; 0.86 for 0-2 years (CI 95 %:0.71-1; p = 0.12); 0.88 for 3-5 years (CI 95 %:0.69-1.11; p = 0.28); 0.61 for 6-11 years (CI 95 %: 0.50-0.75; p < 0.05); and 0.64 for 12-17 years (CI 95 %:0.47-0.89; p < 0.05), consistent with vaccination uptake during the studied period: 63 % for 3-5 years, 91 % for 6-11 years, and 99 % for 12-17 years., Conclusions: A decline of MIS-C incidence and a shift to younger, unvaccinated population overtime was observed. IRR decreased in age-cohorts which achieved high vaccination rates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rodolfo Villena reports a relationship with Sinovac Biotech Ltd that includes: funding grants. Rodolfo Villena reports a relationship with Pfizer that includes: speaking and lecture fees. Rodolfo Villena reports a relationship with Janssen Pharmaceuticals Inc that includes: funding grants. Giannina Izquierdo reports a relationship with Pfizer Inc that includes: speaking and lecture fees. Juan Pablo Torres reports a relationship with Pfizer that includes: speaking and lecture fees If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Published: 2024
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82. Epigenome-Wide Association Studies of Chronic Obstructive Pulmonary Disease and Lung Function: A Systematic Review.

Author: Casas-Recasens S, Cassim R, Mendoza N, Agusti A, Lodge C, Li S, Bui D, Martino D, Dharmage SC, and Faner R
Subjects: Humans, Epigenesis, Genetic, Female, Male, Lung physiopathology, Respiratory Function Tests, Middle Aged, Gene-Environment Interaction, Aged, Pulmonary Disease, Chronic Obstructive genetics, Pulmonary Disease, Chronic Obstructive physiopathology, DNA Methylation genetics, Genome-Wide Association Study, Epigenome genetics
Abstract: Rationale: Chronic obstructive pulmonary disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as DNA methylation. Objectives: To systematically review the evidence form epigenome-wide association studies related to COPD and lung function. Methods: A systematic literature search performed on PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases identified 1,947 articles that investigated epigenetic changes associated with COPD and/or lung function; 17 of them met our eligibility criteria, from which data were manually extracted. Differentially methylated positions (DMPs) and/or annotated genes were considered replicated if identified by two or more studies with a P < 1 × 10 -4 . Measurements and Main Results: Ten studies profiled DNA methylation changes in blood and seven in respiratory samples, including surgically resected lung tissue ( n = 3), small airway epithelial brushings ( n = 2), BAL ( n = 1), and sputum ( n = 1). Main results showed: 1 ) high variability in study design, covariates, and effect sizes, which prevented a formal meta-analysis; 2 ) in blood samples, 51 DMPs were replicated in relation to lung function and 12 related to COPD; 3 ) in respiratory samples, 42 DMPs were replicated in relation to COPD but none in relation to lung function; and 4 ) in COPD versus control studies, 123 genes (2.6% of total) were shared between one or more blood and one or more respiratory samples and associated with chronic inflammation, ion transport, and coagulation. Conclusions: There is high heterogeneity across published COPD and/or lung function epigenome-wide association studies. A few genes ( n = 123; 2.6%) were replicated in blood and respiratory samples, suggesting that blood can recapitulate some changes in respiratory tissues. These findings have implications for future research. Systematic Review [protocol] registered with Open Science Framework (OSF).
Published: 2024
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83. Early experience with targeted and combination biopsies in prostate cancer work-up in Denmark from 2012 to 2016.

Author: Blak AA, Stroomberg HV, Brasso K, Larsen SB, and Røder A
Subjects: Humans, Male, Denmark epidemiology, Middle Aged, Aged, Prostatectomy methods, Biopsy, Time Factors, Prostate pathology, Prostatic Neoplasms pathology, Prostatic Neoplasms surgery, Neoplasm Grading
Abstract: Purpose: To investigate the early implementation of combined systematic and targeted (cBx) primary biopsy in prostate cancer diagnosis and define the concordance in Gleason grading (GG) of different biopsy techniques with radical prostatectomy (RP) pathology., Methods: This population-based analysis includes data on all men in Denmark who underwent primary cBx or standalone systematic (sBx) prostate biopsy between 2012 and 2016. Biopsy results were compared to RP pathology if performed within a year. Concordance measurement was estimated using Cohen's Kappa, and the cumulative incidence of cancer-specific death was estimated at 6 years with the Aalen-Johansen estimator., Results: Concordance between biopsy and RP pathology was 0.53 (95CI: 0.43-0.63), 0.38 (95CI: 0.29-0.48), and 0.16 (95CI: 0.11-0.21) for cBx, targeted biopsy (tBx), and sBx, respectively. For standalone sBx and RP, concordance was 0.29 (95CI: 0.27-0.32). Interrelated GG concordance between tBx and sBx was 0.67 (95CI: 0.62-0.71) in cBx. The proportion of correctly assessed GG based on RP pathology was 54% in both cBx and standalone sBx. Incidence of prostate cancer-specific death was 0% regardless of biopsy technique in GG 1, and 22% (95CI: 11-32), 30% (95CI: 15-44), and 19% (95CI: 7.0-30) in GG 5 for cBx, tBx, or sBx, respectively., Conclusion: Overall, the cBx strategy demonstrates higher concordance to RP pathology than the standalone sBx. However, cBx exhibits more overgrading of the GG of RP pathology compared to sBx. Ultimately, the classic grading system does not take change in the diagnostic pathway into account, and grading should be altered accordingly to ensure appropriate treatment., (© 2024. The Author(s).)
Published: 2024
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84. Incidence and risk of arterial and venous thrombotic events in Systemic Lupus Erythematosus patients: a population-based study.

Author: Ojeda-Fernandez L, Calvisi S, Torrigiani G, Tettamanti M, Fortino I, Roncaglioni C, and Baviera M
Abstract: Objectives: Current data on arterial and venous thrombotic events (ATE & VTE) and cardiovascular (CV) risk management in European systemic lupus erythematosus (SLE) population are limited. This study aimed to investigate the incidence and risk of thrombotic events and all-cause death in an Italian SLE cohort over the past decade, along with its pharmacotherapy., Methods: Incident SLE cases between 2010 and 2019 were identified using administrative health databases of the Lombardy Region. The association between SLE and outcomes, compared with age- and sex-matched controls, was reported as incidence rate per 1000 person-years and as adjusted hazard ratios with 95% confidence intervals., Results: Overall, 2133 SLE patients and 21 283 no-SLE individuals were included. A higher incidence rate of ATE (4.22 vs 2.26 1000 PY), VTE (1.85 vs 0.67 1000 PY,) and all-cause death (15.18 vs 6.22 1000 PY) was reported in SLE patients than in those without (p< 0.0001) as well as an increased risk of ATE (HR, 1.65; 95% CI, 1.20-2.26), VTE (HR, 2.25; 95% CI, 1.35-3.74), and all-cause death (HR, 1.81; 95% CI, 1.52-2.15). After SLE diagnoses, hydroxychloroquine and glucocorticoids were prescribed for at least 60% of patients. Additionally, a higher exposure to cardiovascular medications was also seen in SLE patients., Conclusion: Our findings confirmed higher risks of ATE, VTE and all-cause death in SLE patients. While increased CV medications use after SLE diagnoses suggests heightened awareness to CV risk profile, more attention is required to balance SLE disease activity with minimizing exposure to drugs associated with exacerbating CV risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Published: 2024
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85. Corrigendum to "Mitigating heat effects in the workplace with a ventilation jacket: Simulations of the whole-body and local human thermophysiological response with a sweating thermal manikin in a warm-dry environment" [Volume 119, January 2024, 103772].

Author: Del Ferraro S, Falcone T, Morabito M, Bonafede M, Marinaccio A, Gao C, and Molinaro V
Published: 2024
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86. The European Health Data Space can be a boost for research beyond borders.

Author: Ganna A, Carracedo A, Christiansen CF, Di Angelantonio E, Dykstra PA, Dzhambov AM, Eils R, Green S, Schneider KL, Varga TV, Vuorinen AL, Zuccolo L, Rod NH, and Hoeyer K
Published: 2024
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87. Correction: Associations of residential green space with internalizing and externalizing behavior in early childhood.

Author: Hazlehurst MF, Hajat A, Tandon PS, Szpiro AA, Kaufman JD, Tylavsky FA, Hare ME, Sathyanarayana S, Loftus CT, LeWinn KZ, Bush NR, and Karr CJ
Published: 2024
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88. Trends in Nonfatal Overdose Rates Due to Alcohol and Prescription and Illegal Substances in Colombia, 2010-2021.

Author: Santaella-Tenorio J, Zapata-López JS, Fidalgo TM, Tardelli VS, Segura LE, Cerda M, and Martins SS
Abstract: Objectives. To examine drug overdoses in Colombia by type of substance, sex, age, and intent using data from a health surveillance system from 2010 to 2021. Methods. We characterized data by year, type of substance, and sociodemographic variables. We calculated age-adjusted overdose rates by substance type, sex, age groups, and intent. We used Poisson regression models to examine trend differences across sex and age groups. Results. Age-adjusted rates of drug overdoses increased from 8.51 to 40.52 per 100 000 during 2010 to 2021. Men, compared with women, had higher overdose rates for every substance, except for opioids and psychotropics. Drug overdose rates involving cannabis and stimulants increased steadily until 2017 but decreased afterward. Overdose rates involving psychotropic medication increased greatly during 2018 to 2021, mainly because of intentional overdoses in young women. Conclusions. Overdoses involving illegal drugs decreased in recent years in Colombia; however, the continuous increase in intentional psychotropic overdose rates highlights the need for prevention efforts to curb this trend. Health surveillance systems are an important tool that can guide overdose prevention efforts in countries with limited data resources. ( Am J Public Health . Published online ahead of print September 12, 2024:e1-e9. https://doi.org/10.2105/AJPH.2024.307786).
Published: 2024
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89. Interactions of depression, anxiety, and sleep quality with menopausal symptoms on job satisfaction among middle-aged health workers in England: a STROBE-based analysis.

Author: Asiamah N, Cronin C, Abbott JE, and Smith S
Subjects: Humans, Female, Middle Aged, Cross-Sectional Studies, England epidemiology, Adult, Job Satisfaction, Anxiety epidemiology, Anxiety psychology, Menopause psychology, Depression epidemiology, Depression psychology, Health Personnel psychology, Sleep Quality
Abstract: Background: This study examined the association between menopausal symptoms and job satisfaction, and ascertained whether three psychosomatic factors (e.g., anxiety, depression, and sleep quality) interact with menopausal symptoms on job satisfaction., Methods: A cross-sectional design with sensitivity analysis was adopted. The participants of the study were clinical health workers in England. Data from 154 health workers were analyzed with the hierarchical linear regression (HLR) analysis., Results: There was a negative association between menopausal symptoms and job satisfaction (β = -0.38; t = -4.81, p < 0.001), but this relationship became non-significant after adjusting for work stress, self-reported health, job tenure, and resilience at work. An interaction between menopausal symptoms and the psychosomatic factors was found. The strength of the negative association between menopausal symptoms and job satisfaction was weakened by sleep quality (β = 0.05; t = 0.48; p > 0.05) but was strengthened by anxiety (β = -0.22; t = -2.28; p < 0.05) and depression (β = -0.24; t = -2.16; p < 0.05)., Conclusion: Menopausal symptoms can be directly associated with lower job satisfaction and indirectly associated with lower job satisfaction through its interaction with depression and anxiety. Menopausal symptoms can weaken the positive association between sleep quality and job satisfaction., (© 2024. The Author(s).)
Published: 2024
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90. HIF-2α drives hepatic Kupffer cell death and proinflammatory recruited macrophage activation in nonalcoholic steatohepatitis.

Author: Jeelani I, Moon JS, da Cunha FF, Nasamran CA, Jeon S, Zhang X, Bandyopadhyay GK, Dobaczewska K, Mikulski Z, Hosseini M, Liu X, Kisseleva T, Brenner DA, Singh S, Loomba R, Kim M, and Lee YS
Subjects: Animals, Mice, Cell Death, Lysosomes metabolism, Phagocytosis, Humans, Reactive Oxygen Species metabolism, Inflammation pathology, Inflammation metabolism, Mice, Inbred C57BL, TOR Serine-Threonine Kinases metabolism, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism, Macrophages metabolism, Mitochondria metabolism, Kupffer Cells metabolism, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, Macrophage Activation, Basic Helix-Loop-Helix Transcription Factors metabolism, Liver metabolism, Liver pathology
Abstract: Proinflammatory hepatic macrophage activation plays a key role in the development of nonalcoholic steatohepatitis (NASH). This involves increased embryonic hepatic Kupffer cell (KC) death, facilitating the replacement of KCs with bone marrow-derived recruited hepatic macrophages (RHMs) that highly express proinflammatory genes. Moreover, phago/efferocytic activity of KCs is diminished in NASH, enhancing liver inflammation. However, the molecular mechanisms underlying these changes in KCs are not known. Here, we show that hypoxia-inducible factor 2α (HIF-2α) mediates NASH-associated decreased KC growth and efferocytosis by enhancing lysosomal stress. At the molecular level, HIF-2α stimulated mammalian target of rapamycin (mTOR)- and extracellular signal-regulated kinase-dependent inhibitory transcription factor EB (TFEB) phosphorylation, leading to decreased lysosomal and phagocytic gene expression. With increased metabolic stress and phago/efferocytic burden in NASH, these changes were sufficient to increase lysosomal stress, causing decreased efferocytosis and lysosomal cell death. Of interest, HIF-2α-dependent TFEB regulation only occurred in KCs but not RHMs. Instead, in RHMs, HIF-2α promoted mitochondrial reactive oxygen species production and proinflammatory activation by increasing ANT2 expression and mitochondrial permeability transition. Consequently, myeloid lineage-specific or KC-specific HIF-2α depletion or the inhibition of mTOR-dependent TFEB inhibition using antisense oligonucleotide treatment protected against the development of NASH in mice. Moreover, treatment with an HIF-2α-specific inhibitor reduced inflammatory and fibrogenic gene expression in human liver spheroids cultured under a NASH-like condition. Together, our results suggest that macrophage subtype-specific effects of HIF-2α collectively contribute to the proinflammatory activation of liver macrophages, leading to the development of NASH.
Published: 2024
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91. A pragmatic randomized trial to examine the effect of combining healthy diet with mindfulness cognitive therapy to reduce depressive symptoms among university students in a low-resource setting: protocol for the NutriMind Project.

Author: Kardel KR, Iversen PO, Kaaya AN, Muhoozi G, Veierød MB, Wangen KR, Børøsund E, and Friberg PA
Subjects: Humans, Uganda, Universities, Male, Female, Young Adult, Adult, Combined Modality Therapy methods, Pragmatic Clinical Trials as Topic, Mindfulness methods, Depression therapy, Depression prevention & control, Depression psychology, Students psychology, Diet, Healthy methods, Diet, Healthy psychology
Abstract: Background: Mental health disorders still rank as leading causes of morbidity worldwide despite increasing awareness and improvements in treatment. Notably, low- and middle-income countries like Uganda, are disproportionately affected by such disorders. The burden of depressive symptoms in these countries is particularly high among students, aggravated by poverty, malnutrition, and inadequate public health governance, yet it is clearly under-researched, making it hard to achieve several of UN Sustainability Development Goals. Current treatment options are insufficient to tackle the increased burden of depressive disease. This is more challenging for low-resource regions especially in Sub-Saharan Africa, suggesting the need for alternative treatments that can swiftly be applied if proven effective. The main aim of this randomized controlled trial (RCT) is therefore to examine if a low-cost healthy diet (based on local Ugandan foods) combined with easy-to access mindfulness cognitive therapy can reduce depressive symptoms among university students in Uganda., Methods: We will recruit female and male students at Makerere University, the largest public university in Uganda, to an open, intention-to-treat, two-armed RCT. Those who score above a predefined threshold on a self-reported assessment of depressive symptoms, measured by the Center for Epidemiological Studies - Depression score (CES-D), are eligible for study inclusion and will be randomized to either an intervention (n = 125) or a control (n = 125) group. The intervention group will receive educational group-based sessions on how to prepare a Mediterranean-type of healthy diet and how to adhere to the principles of mindfulness-based cognitive therapy. Outcome measures include self-reported depression symptoms, quality of life, and dietary intakes. In addition we will perform a cost-effectiveness analysis. The RCT intervention will last 9 months, followed by additional 15 months with regular data collections., Discussion: We here describe a novel approach to treat depressive symptoms among university students living in resource constraint settings, by combining a healthy diet with low threshold psychotherapy. If this intervention succeeds, our project can be viewed as a step towards evidence-based behavior practices for young adults with a common mental disorder (depression) that are beneficial to public mental health initiatives and management., Trial Registration: The RCT is registered in ClinicalTrials.gov (ID: NCT05848973). The date of registration was August 14, 2023., (© 2024. The Author(s).)
Published: 2024
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92. Genetic links between ovarian ageing, cancer risk and de novo mutation rates.

Author: Stankovic S, Shekari S, Huang QQ, Gardner EJ, Ivarsdottir EV, Owens NDL, Mavaddat N, Azad A, Hawkes G, Kentistou KA, Beaumont RN, Day FR, Zhao Y, Jonsson H, Rafnar T, Tragante V, Sveinbjornsson G, Oddsson A, Styrkarsdottir U, Gudmundsson J, Stacey SN, Gudbjartsson DF, Kennedy K, Wood AR, Weedon MN, Ong KK, Wright CF, Hoffmann ER, Sulem P, Hurles ME, Ruth KS, Martin HC, Stefansson K, Perry JRB, and Murray A
Abstract: Human genetic studies of common variants have provided substantial insight into the biological mechanisms that govern ovarian ageing 1 . Here we report analyses of rare protein-coding variants in 106,973 women from the UK Biobank study, implicating genes with effects around five times larger than previously found for common variants (ETAA1, ZNF518A, PNPLA8, PALB2 and SAMHD1). The SAMHD1 association reinforces the link between ovarian ageing and cancer susceptibility 1 , with damaging germline variants being associated with extended reproductive lifespan and increased all-cause cancer risk in both men and women. Protein-truncating variants in ZNF518A are associated with shorter reproductive lifespan-that is, earlier age at menopause (by 5.61 years) and later age at menarche (by 0.56 years). Finally, using 8,089 sequenced trios from the 100,000 Genomes Project (100kGP), we observe that common genetic variants associated with earlier ovarian ageing associate with an increased rate of maternally derived de novo mutations. Although we were unable to replicate the finding in independent samples from the deCODE study, it is consistent with the expected role of DNA damage response genes in maintaining the genetic integrity of germ cells. This study provides evidence of genetic links between age of menopause and cancer risk., (© 2024. The Author(s).)
Published: 2024
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93. Impact of a 12-week high-intensity interval training intervention on cardiac structure and function after COVID-19 at 12-month follow-up.

Author: Rasmussen IE, Løk M, Durrer CG, Lytzen AA, Foged F, Schelde VG, Budde JB, Rasmussen RS, Høvighoff EF, Rasmussen V, Lyngbæk M, Jønck S, Krogh-Madsen R, Lindegaard B, Jørgensen PG, Køber L, Vejlstrup N, Pedersen BK, Ried-Larsen M, Lund MAV, Berg RMG, and Christensen RH
Abstract: In patients previously hospitalised for COVID-19, a 12-week high-intensity interval training (HIIT) intervention has previously been shown to increase left ventricular mass (LVM) immediately after the intervention. In the present study, we examined the effects of the same HIIT scheme on LVM, pulmonary diffusing capacity, symptom severity and functional capacity at 12-month follow-up. In this investigator-blinded, randomised controlled trial, 12 weeks of a supervised HIIT scheme (4 × 4 min, three times a week) was compared to standard care (control) in patients recently discharged from hospital due to COVID-19. At inclusion and at 12-month follow-up, LVM was assessed by cardiac magnetic resonance imaging (cMRI, primary outcome), while pulmonary diffusing capacity for carbon monoxide (D LCOc , secondary outcome) was examined by the single-breath method. Symptom severity and functional status were examined by the Post-COVID-19 Functional Scale (PCFS) and King's Brief Interstitial Lung Disease (KBILD) questionnaire score. Of the 28 patients assessed at baseline, 22 completed cMRI at 12-month follow-up (12.4 ± 0.6 months after inclusion). LVM was maintained in the HIIT but not the standard care group, with a mean between-group difference of 9.68 [95% CI: 1.72, 17.64] g (P = 0.0182). There was no differences in change from baseline to 12-month follow-up between groups in D LCOc % predicted (-2.45 [-11.25, 6.34]%; P = 0.578). PCFS and KBILD improved similarly in the two groups. In individuals previously hospitalised for COVID-19, a 12-week supervised HIIT scheme resulted in a preserved LVM at 12-month follow-up but did not affect pulmonary diffusing capacity or symptom severity., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)
Published: 2024
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94. Increases in amyloid-β42 slow cognitive and clinical decline in Alzheimer's disease trials.

Author: Abanto J, Dwivedi AK, Imbimbo BP, and Espay AJ
Abstract: Positive effects of new anti-amyloid-β (Aβ) monoclonal antibodies in Alzheimer's disease (AD) have been attributed to brain amyloid reduction. However, most anti-Aβ antibodies also increase the CSF levels of the 42-amino acid isoform (Aβ42). We evaluated the associations of changes in CSF Aβ42 and brain Aβ-PET with cognitive and clinical end points in randomized trials of anti-Aβ drugs that lowered (β- and γ-secretase inhibitors) or increased CSF Aβ42 levels (anti-Aβ monoclonal antibodies) to test the hypothesis that post-treatment increases in CSF Aβ42 levels are independently associated with cognitive and clinical outcomes. From long-term (≥12 months) randomized placebo-controlled clinical trials of anti-Aβ drugs published until November 2023, we calculated the post-treatment versus baseline difference in ADAS-Cog (cognitive subscale of the Alzheimer's Disease Assessment Scale) and CDR-SB (Clinical Dementia Rate-Sum of Boxes) and z-standardized changes in CSF Aβ42 and Aβ-PET Centiloids (CL). We estimated the effect size [regression coefficients (RCs) and confidence intervals (CIs)] and the heterogeneity (I2) of the associations between AD biomarkers and cognitive and clinical end points using random-effects meta-regression models. We included 25 966 subjects with AD from 24 trials. In random-effects analysis, increases in CSF Aβ42 were associated with slower decline in ADAS-Cog (RC: -0.55; 95% CI: -0.89, -0.21, P = 0.003, I2 = 61.4%) and CDR-SB (RC: -0.16; 95% CI: -0.26, -0.06, P = 0.002, I2 = 34.5%). Similarly, decreases in Aβ-PET were associated with slower decline in ADAS-Cog (RC: 0.69; 95% CI: 0.48, 0.89, P < 0.001, I2 = 0%) and CDR-SB (RC: 0.26; 95% CI: 0.18, 0.33, P < 0.001, I2 = 0%). Sensitivity analyses yielded similar results. Higher CSF Aβ42 levels after exposure to anti-Aβ drugs are independently associated with slowing cognitive impairment and clinical decline. Increases in Aβ42 may represent a mechanism of potential benefit of anti-Aβ monoclonal antibodies in AD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Published: 2024
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95. Bidirectional Mendelian Randomization to Elucidate the Relationship Between Healthy Sleep, Brains, and Hearts.

Author: Wolford BN and Åsvold BO
Published: 2024
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96. Trends in Racial/Ethnic Disparities in Early Glycemic Control Among Veterans Receiving Care in the Veterans Health Administration, 2008-2019.

Author: Hua S, Kanchi R, Anthopolos R, Schwartz MD, Pendse J, Titus AR, and Thorpe LE
Abstract: Objective: Racial/ethnic disparities in glycemic control among non-Hispanic Black (NHB) and non-Hispanic White (NHW) veterans with type 2 diabetes (T2D) have been reported. This study examined trends in early glycemic control by race/ethnicity to understand how disparities soon after T2D diagnosis have changed between 2008 and 2019 among cohorts of U.S. veterans with newly diagnosed T2D., Research Design and Methods: We estimated the annual percentage of early glycemic control (average A1C <7%) in the first 5 years after diagnosis among 837,023 veterans (95% male) with newly diagnosed T2D in primary care. We compared early glycemic control by racial/ethnic group among cohorts defined by diagnosis year (2008-2010, 2011-2013, 2014-2016, and 2017-2018) using mixed-effects models with random intercepts. We estimated odds ratios of early glycemic control comparing racial/ethnic groups with NHW, adjusting for age, sex, and years since diagnosis., Results: The average annual percentage of veterans who achieved early glycemic control during follow-up was 73%, 72%, 72%, and 76% across the four cohorts, respectively. All racial/ethnic groups were less likely to achieve early glycemic control compared with NHW veterans in the 2008-2010 cohort. In later cohorts, NHB and Hispanic veterans were more likely to achieve early glycemic control; however, Hispanic veterans were also more likely to have an A1C ≥9% within 5 years in all cohorts. Early glycemic control disparities for non-Hispanic Asian, Native Hawaiian/Pacific Islander, and American Indian/Alaska Native veterans persisted in cohorts until the 2017-2018 cohort., Conclusions: Overall early glycemic control trends among veterans with newly diagnosed T2D have been stable since 2008, but trends differed by racial/ethnic groups and disparities in very poor glycemic control were still observed. Efforts should continue to minimize disparities among racial/ethnic groups., (© 2024 by the American Diabetes Association.)
Published: 2024
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97. Publisher Correction: A plasma protein-based risk score to predict hip fractures.

Author: Austin TR, Nethander M, Fink HA, Törnqvist AE, Jalal DI, Buzkova P, Barzilay JI, Carbone L, Gabrielsen ME, Grahnemo L, Lu T, Hveem K, Jonasson C, Kizer JR, Langhammer A, Mukamal KJ, Gerszten RE, Psaty BM, Robbins JA, Sun YV, Skogholt AH, Kanis JA, Johansson H, Åsvold BO, Valderrabano RJ, Zheng J, Richards JB, Coward E, and Ohlsson C
Published: 2024
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98. Disinfection byproducts in US drinking water and cancer mortality.

Author: Mendy A
Abstract: Trihalomethanes, the main drinking water disinfection byproducts, may be carcinogenic and are regulated to amaximum total trihalomethanes (TTHM) of 80 µg/l in the US. We aimed to determine whether total and individual trihalomethanes in drinking water across the US are associated with higher cancer mortality in 6,260 adult participants to the National Health and Nutrition Examination Surveys from 1999 to 2008 followed for mortality until 2019 (median: 14.4 years). At baseline, the geometric mean (standard error) of TTHM in drinking water was 9.61 (0.85) µg/l. During follow-up, 873 deaths occurred, including 207 from cancer. In Cox proportional hazards regression adjusted for relevant covariates, drinking water TTHM (HR: 1.45, 95% CI: 1.16-1.82), chloroform (HR: 1.35, 95% CI: 1.12-1.64), and bromodichloromethane (HR: 1.30, 95% CI: 1.05-1.59) were associated with 30% to 45% higher cancer mortality. Therefore, drinking water trihalomethanes, especially chloroform and bromodichloromethane maybe risk factors for cancer mortality.
Published: 2024
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99. Timely targeted testing for hereditary cancer syndromes - Importance of clinician-facilitated cascade testing in the first year post-diagnosis.

Author: Grant B, Raghunandan A, Epstein E, Brewer JT, Chandler I, Larosa T, Kalyan A, Schulman S, Llenas A, Chapman-Davis E, Thomas C, Christos P, Lipkin SM, Sharaf RN, and Frey MK
Abstract: Objective: Cascade testing for hereditary cancer syndromes allows relatives to estimate cancer risk and pursue prevention and early detection strategies. The current paradigm relies on patient coordinated care, resulting in only one-third of relatives successfully completing testing. Studies suggest that team-based approaches, where clinicians facilitate testing, can increase uptake. As institutions consider implementing such programs, understanding patient characteristics associated with interest is crucial for resource allocation. We aim to assess interest in clinician-facilitated testing and evaluate barriers., Methods: Patients with cancer-associated pathogenic variants seen at a gynecologic oncology clinic were offered clinician-facilitated cascade testing. Patient interest and demographic variables were recorded and patients that declined were interviewed regarding the decision., Results: From 11/2023-4/2024, 139 patients were offered clinician-facilitated cascade testing. Median patient age was 43 years (IQR 17), 97 (69.8 %) self-identified as White and 101 (72.7 %) as non-Hispanic. Fifty-six (40.3 %) patients harbored a BRCA1 pathogenic variant, 37 (26.6 %) BRCA2, and 46 (33.1 %) other cancer-associated genes. Fifty-seven (41.0 %) patients expressed interest in the intervention. Interested patients were more likely to have been diagnosed in the prior year vs. patients who were not interested on univariate (OR 4.6, 95 % CI 2.0-10.2, P = 0.0002) and multivariable analyses (adjusted OR 3.8, 95 % CI 1.622-9.009, P = 0.0022)., Conclusions: Our study demonstrates that patients are almost five time more likely to be interested in cascade genetic testing within the first year of diagnosis of a pathogenic variant. Given the utility of such programs and their resource requirements, targeting this population could maximize effectiveness and uptake of cascade services., Competing Interests: Declaration of competing interest The authors have no financial or personal conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)
Published: 2024
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100. Predicting antibiotic resistance in Enterobacterales to support optimal empiric treatment of urinary tract infections in outpatient veterans.

Author: Brintz BJ, Madaras-Kelly K, Nevers M, Echevarria KL, Goetz MB, and Samore MH
Abstract: Objective: Bacterial resistance is known to diminish the effectiveness of antibiotics for treatment of urinary tract infections. Review of recent healthcare and antibiotic exposures, as well as prior culture results is recommended to aid in selection of empirical treatment. However, the optimal approach for assessing these data is unclear. We utilized data from the Veterans Health Administration to evaluate relationships between culture and treatment history and the subsequent probability of antibiotic-resistant bacteria identified in urine cultures to further guide clinicians in understanding these risk factors., Methods: Using the XGBoost algorithm, a retrospective cohort of outpatients with urine culture results and antibiotic prescriptions from 2017 to 2022 was used to develop models for predicting antibiotic resistance for three classes of antibiotics: cephalosporins, fluoroquinolones, and trimethoprim/sulfamethoxazole (TMP/SMX) obtained from urine cultures. Model performance was assessed using Area Under the Receiver Operating Characteristic curve (AUC) and Precision-Recall AUC (PRAUC)., Results: There were 392,647 prior urine cultures identified in 214,656 patients. A history of bacterial resistance to the specific treatment was the most important predictor of subsequent resistance for positive cultures, followed by a history of specific antibiotic exposure. The models performed better than previously established risk factors alone, especially for fluoroquinolone resistance, with an AUC of .84 and PRAUC of .70. Notably, the models' performance improved markedly (AUC = .90, PRAUC = .87) when applied to cultures from patients with a known history of resistance to any of the antibiotic classes., Conclusion: These predictive models demonstrate potential in guiding antibiotic prescription and improving infection management., Competing Interests: The authors report no relevant conflicts of interest., (© The Author(s) 2024.)
Published: 2024
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