title: Reproductive windows, genetic loci, and breast cancer risk.
abstract: OBJECTIVE
  The 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  For 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.
  
  
  CONCLUSIONS
  Our results suggest that the reproductive windows are associated with breast cancer risk and that associations may vary by genetic variants.
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison; Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison. Electronic address: snandersen@uwalumni.com.
authors.forename: Shaneda
authors.initials: S
authors.lastname: Warren Andersen
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison; Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Amy
authors.initials: A
authors.lastname: Trentham-Dietz
authors.affiliation: Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gangnon
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison.
authors.forename: John M
authors.initials: JM
authors.lastname: Hampton
authors.affiliation: Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.affiliation: Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Halcyon G
authors.initials: HG
authors.lastname: Skinner
authors.affiliation: Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Corinne D
authors.initials: CD
authors.lastname: Engelman
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Klein
authors.affiliation: Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Titus
authors.affiliation: Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Egan
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison; Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000209:etiology* / Q000235:genetics; D018275:Carcinoma, Lobular / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008423:Maternal Age; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D016017:Odds Ratio; D036801:Parturition; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012307:Risk Factors
keywords: Breast neoplasms; Epidemiology; Genetic loci; Histology; Menarche; Menopause