Reproductive windows,genetic loci,and breast cancer risk |
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| Affiliation: | 1. University of Wisconsin Carbone Cancer Center, Madison;2. Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison;3. Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD;4. Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison;5. Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH;6. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL;7. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA;1. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA;2. Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA;3. Division of Health Protection, Georgia Department of Public Health, Atlanta, GA;4. Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA;1. Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA;2. Division of Newborn Medicine, Boston Children''s Hospital, MA;3. Harvard Medical School, Boston, MA;4. Obesity Prevention Program, Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA;5. Division of Gastroenterology and Nutrition, Boston Children''s Hospital, MA;6. Channing Division of Network Medicine, Department of Medicine, Brigham and Women''s Hospital, Boston, MA;7. Division of Pulmonary and Critical Care, Brigham and Women''s Hospital, Boston, MA;8. Division of Women''s Health, Department of Medicine, Brigham and Women''s Hospital, Boston, MA;9. Department of Epidemiology, Harvard School of Public Health, Boston, MA;10. Department of Emergency Medicine, Massachusetts General Hospital, Boston;11. Department of Nutrition, Harvard School of Public Health, Boston, MA;1. Department of Epidemiology, University of Michigan, Ann Arbor;2. Department of Biostatistics, University of Michigan, Ann Arbor;3. Department of Epidemiology, University of Michigan, Ann Arbor;4. Department of Environmental Health Sciences, University of Michigan, Ann Arbor;1. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark;2. Department of Cardiology, Aarhus University Hospital, Skejby, Denmark;1. Department of Neurology, Mount Sinai School of Medicine, New York, NY;2. Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY;3. Department of Neurology, Evelyn F. McKnight Brain Institute, Miller School of Medicine, University of Miami, FL;4. Department of Public Health Sciences and Human Genetics, Miller School of Medicine, University of Miami, FL;5. Department of Human Genetics, Miller School of Medicine, University of Miami, FL;6. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY |
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| Abstract: | PurposeThe reproductive windows between age at menarche and age at first birth (standardized age at first birth) and from menarche to menopause (reproductive lifespan) may interact with genetic variants in association with breast cancer risk.MethodsWe assessed this hypothesis in 6131 breast cancer cases and 7274 controls who participated in the population-based Collaborative Breast Cancer Study. Risk factor information was collected through telephone interviews, and DNA samples were collected on a subsample (N= 1484 cases, 1307 controls) to genotype for 13 genome-wide association study-identified loci. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and P values for the interaction between reproductive windows and genotypes were obtained by adding cross-product terms to statistical models.ResultsFor standardized age at first birth, the OR was 1.52 (CI, 1.36–1.71) comparing the highest quintile with the lowest quintile. Carrier status for rs10941679 (5p12) and rs10483813 (RAD51B) appeared to modify this relationship (P = .04 and P = .02, respectively). For reproductive lifespan, the OR comparing the highest quintile with the lowest quintiles was 1.62 (CI, 1.35–1.95). No interactions were detected between genotype and reproductive lifespan (all P > .05). All results were similar regardless of ductal versus lobular breast cancer subtype.ConclusionsOur results suggest that the reproductive windows are associated with breast cancer risk and that associations may vary by genetic variants. |
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| Keywords: | Breast neoplasms Epidemiology Menarche Menopause Genetic loci Histology |
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