Journal
PLOS GENETICS
Volume 9, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1003284
Keywords
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Categories
Funding
- Cancer Research UK [C1287/A10118, C1287/A12014, C490/A6187, C490/A10119, C490/A10124]
- European Community [223175 (HEALTH-F2-2009-223175)]
- European Union COST programme [BM0606]
- Fondo de Investigacion Sanitario [PI11/00923]
- Australian NHMRC
- New South Wales Cancer Council
- Victorian Health Promotion Foundation (Australia)
- National Cancer Institute, National Institutes of Health under RFA [CA-06-503]
- BCFR and Principal Investigators
- Cancer Care Ontario [U01 CA69467]
- Columbia University [U01 CA69398]
- Fox Chase Cancer Center [U01 CA69631]
- Huntsman Cancer Institute [U01 CA69446]
- Cancer Prevention Institute of California [U01 CA69417]
- University of Melbourne [U01 CA69638]
- Georgetown University Medical Center Informatics Support Center [HHSN261200900010C]
- ELAN-Fond of the University Hospital of Erlangen
- Cancer Research UK
- Breakthrough Breast Cancer
- NHS
- National Cancer Research Network (NCRN)
- Fondation de France
- French National Institute of Cancer (INCa)
- National League against Cancer
- National Agency for Environmental and Occupational Health and Food Safety (ANSES)
- National Agency for Research (ANR)
- Association for Research against Cancer (ARC)
- Chief Physician Johan Boserup and Lise Boserup Fund
- Danish Medical Research Council
- Herlev Hospital
- California Breast Cancer Act of 1993
- National Institutes of Health [R01 CA77398]
- Lon V Smith Foundation [LVS39420]
- California Breast Cancer Research Fund [97-10500]
- Baden Wurttemberg Ministry of Science, Research and Arts
- German Cancer Aid (Deutsche Krebshilfe)
- Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]
- Robert Bosch Foundation, Stuttgart
- Deutsches Krebsforschungszentrum (DKFZ), Heidelberg
- Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum
- Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany
- Deutsche Krebshilfe e.V. [70492, 70-2892-BR I]
- Government Funding (EVO) of Kuopio University Hospital
- Cancer Fund of North Savo
- Finnish Cancer Organizations
- Academy of Finland
- University of Eastern Finland
- National Breast Cancer Foundation
- NHMRC
- Queensland Cancer Fund
- Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia
- Cancer Foundation of Western Australia
- NHMRC [145684, 288704, 454508, 199600]
- United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]
- Cancer Council of Tasmania and Cancer Foundation of Western Australia
- Stichting tegen Kanker [232-2008, 196-2010]
- Hamburg Cancer Society
- German Cancer Research Center
- NIH [CA122340, CA128978]
- Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]
- Australian NHMRC [209057, 251553, 504711]
- National Cancer Institute, Department of Health and Human Services, USA
- Agency for Science, Technology and Research of Singapore (A*STAR)
- U.S. National Institute of Health (NIH)
- Susan G. Komen Breast Cancer Foundation
- Marit and Hans Rausings Initiative Against Breast Cancer
- Yorkshire Cancer Research and the Breast Cancer Campaign
- UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge
- Massachusetts (KME) [R01CA47305]
- Wisconsin (PAN) [R01 CA47147]
- New Hampshire (LT-E) [R01CA69664]
- Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, USA
- Cancer Research UK [16565, 11022, 16561, 10118] Funding Source: researchfish
- Cancer Research UK
- The Francis Crick Institute [10124] Funding Source: researchfish
- National Breast Cancer Foundation [IF-12-06] Funding Source: researchfish
Ask authors/readers for more resources
Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (P-interaction = 2.4 x 10(-6)) and between CASP8-rs17468277 and alcohol consumption (P-interaction = 3.1 x 10(-4)). Overall, the perallele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank >= 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (P-interaction = 5.3 x 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.
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