Estrogen Receptor Alpha Gene Polymorphisms and Breast Cancer Risk: a Case-control Study with Meta-analysis Combined

Molecular epidemiological studies have shown that gene polymorphisms of estrogen receptor alpha gene(ESR-α) are associated with breast cancer risk. However, previous results from many molecular studies havebeen inconsistent. In this study, we examined two polymorphisms (PvuII and XbaI RFLPs) of the ESR-αgene in 542 breast cancer cases and 1,016 controls from China. Associations between the polymorphisms andbreast cancer risk were calculated with an unconditional logistic regression model. Linkage disequilibrium andhaplotypes were analyzed with the SHEsis software. In addition, we also performed a systematic meta-analysisof 24 published studies evaluating the association. No significant associations were found between the PvuIIpolymorphism and breast cancer risk. However, a significantly decreased risk of breast cancer was observedamong carriers of the XbaI ‘G’ allele (age-adjusted OR = 0.80; 95% CI = 0.66- 0.97) compared with carriers ofthe ‘A’ allele. Haplotype analysis showed significantly decreased cancer risk for carriers of the ‘CG’ haplotype(OR = 0.79; 95% CI = 0.66- 0.96). In the systematic meta-analysis, the XbaI ‘G’ allele was associated with anoverall significantly decreased risk of breast cancer (OR = 0.90, 95% CI = 0.82- 1.00). In addition, the PvuII‘C’ allele showed a 0.96- fold decreased disease risk (95% CI = 0.92- 0.99). In subgroup analysis, an associationbetween the PvuII ‘C’ and XbaI ‘G’ alleles and breast cancer risk was significant in Asians (‘C’ vs. ‘T’: OR =0.93, 95% CI = 0.85- 1.00; ‘G’ vs. ‘A’: OR = 0.82, 95% CI = 0.68- 0.98), but not in Euro-Americans. Thus, ourresults provide evidence that ESR-α polymorphisms are associated with susceptibility to breast cancer. Theseassociations may largely depend on population characteristics and geographic location.