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Association of estrogen receptor α polymorphisms with breast cancer risk in older Caucasian women
Author(s) -
Modugno Francesmary,
Zmuda Joseph M.,
Potter Douglas,
Cai Chao,
Ziv Elad,
Cummings Steven R.,
Stone Katie L.,
Morin Phillip A.,
Greene Deborah,
Cauley Jane A.
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21105
Subject(s) - breast cancer , hazard ratio , medicine , estrogen receptor , genotype , estrogen receptor alpha , estrogen , confidence interval , proportional hazards model , oncology , gynecology , allele , prospective cohort study , cancer , endocrinology , biology , genetics , gene
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. © 2005 Wiley‐Liss, Inc.