Potentially functional polymorphisms in ESR1 and breast cancer risk: a meta-analysis.

Estrogen exposure is a central risk factor in the development of breast cancer. Estrogen receptor alpha (coded by ESR1) is the key mediator of estrogen response in mammary tissue. Genetic changes altering the expression of ESR1 is likely to affect breast cancer susceptibility. Since the identification of several potentially functional polymorphisms in ESR1 (rs2234693, rs9340799, rs1801132, rs3798577, rs2228480), molecular epidemiological studies were conducted in recent years to evaluate the association between polymorphisms and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This current analysis on 10,300 breast cancer cases and 16,620 controls on rs2234693 showed a borderline significant decreased breast cancer risk for CC and CC/CT carriers (CC vs. TT: OR, 0.92, 95% CI, 0.86-0.99; CC/CT vs. TT: OR, 0.95, 95% CI, 0.89-1.00). Variant genotypes of the rs1801132 polymorphism were also associated with a decreased breast cancer risk in a dominant model in 5,649 cases and 6,856 controls (GG/GC vs. CC: OR, 0.92, 95% CI, 0.85-0.99). These results suggest that potentially functional ESR1 polymorphisms may play a low penetrance role in breast cancer susceptibility. SNPs rs9340799, rs3798577, rs2228480, and rs2077647 in ESR1 were not causative SNPs. SNPs rs2747648, rs1062577, and rs3020314 were recommended in further association studies and functional evaluations.