Association of estrogen receptor alpha polymorphisms with breast cancer risk in older Caucasian women.
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.
Modugno
Francesmary
F
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. modugno+@pitt.edu
Zmuda
Joseph M
JM
Potter
Douglas
D
Cai
Chao
C
Ziv
Elad
E
Cummings
Steven R
SR
Stone
Katie L
KL
Morin
Phillip A
PA
Greene
Deborah
D
Cauley
Jane A
JA
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*
D047628:Estrogen Receptor alpha