title: Association of estrogen receptor alpha polymorphisms with breast cancer risk in older Caucasian women.
abstract: Estrogens exert their effect on the breast through the estrogen receptor. We prospectively investigated breast cancer risk associated with 2 polymorphic sites in the estrogen receptor alpha gene (ESR1). A total of 4,248 Caucasian women from the Study of Osteoporotic Fractures were genotyped for the -401 T/C and -354 A/G polymorphisms in ESR1. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between genotypes and breast cancer. During a mean follow-up of 12.4 years, 252 (5.9%) women developed breast cancer. The HR (95% CI) for breast cancer were 0.928 (0.708, 1.22) and 0.834 (0.538, 1.29) for the -354 A/G and A/A genotypes, respectively. Interactions with -354 variant were observed for smoking (HR = 1.52 and 1.56 for A/G and A/A smokers, respectively; HR = 0.74 and 0.60 for A/G and A/A non-smokers, respectively; interaction p = 0.03) and walking (HR = 0.75 and 1.15 for A/G and A/A walkers, respectively; HR = 0.18 and 0.49 for A/G and A/A non-walkers, respectively; interaction p = 0.01). There were no differences in the HR for the -401 T/C genotypes. An interaction between parity and carriage of the T allele was found (HR = 0.60 vs. 1.12 for nulliparous vs. parous women; interaction p = 0.03). ESR1 polymorphisms in combination with lifestyle factors may be associated with breast cancer risk in older Caucasian women.
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. modugno+@pitt.edu
authors.forename: Francesmary
authors.initials: F
authors.lastname: Modugno
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Zmuda
authors.forename: Douglas
authors.initials: D
authors.lastname: Potter
authors.forename: Chao
authors.initials: C
authors.lastname: Cai
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.forename: Katie L
authors.initials: KL
authors.lastname: Stone
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Morin
authors.forename: Deborah
authors.initials: D
authors.lastname: Greene
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D016001:Confidence Intervals; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008019:Life Style; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D016016:Proportional Hazards Models; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: D047628:Estrogen Receptor alpha