Association of repeat polymorphisms in the estrogen receptors alpha, beta (ESR1, ESR2) and androgen receptor (AR) genes with the occurrence of breast cancer

Genetic variation in genes involved in estrogen biosynthesis, metabolism and signal transduction have been suggested to play a role in breast cancer. To determine the possible contribution of genetic variation in the ESR1 (ER-α), ESR2 (ER-β) and AR genes in breast cancer risk the −1174(TA)7–27, c. 1092+3607(CA)10−26 and c. 172(CAG)6−40 repeat variants were studied in a case-control study of 79 women with sporadic breast cancer and 155 controls. No significant difference was observed in the frequency distribution of −1174(TA)7−27 in the ESR1 gene between patients and controls, while a significant difference was observed for repeat polymorphisms c. 1092+3607(CA)10−26 in the ESR2 gene and c. 172(CAG)6−40 in the AR gene (p⩽0.0001). A significantly decreased odds ratio (OR) for breast cancer risk was observed in individuals having the LL and the SL genotypes for both the ESR2 (OR=0.010, 95% CI 0.003–0.036, p<0.001; OR=0.013, 95% CI 0.004–0.040, p<0.0001, respectively) and the AR gene (OR=0.040, 95% CI 0.011–0.138, p<0.0001; OR=0.189, 95% CI 0.10–0.359, p<0.0001, respectively), compared to SS genotype. The protective effect of these genotypes remained evident even after adjustment for various risk factors (BMI, age, age at menarche and menopause, family history). In conclusion, an association for breast cancer risk between short (SS) alleles for the repeat variants of the ESR2 and AR genes was found in women of Greek descent.