Haplotype analysis of XRCC1 (at codons 194 and 399) and susceptibility to breast cancer, a meta-analysis of the literatures

To clarify the association between XRCC1 haplotypes and susceptibility to breast cancer, a meta-analysis of case–control studies were conducted. Eligible studies were identified by searching several databases for relevant reports published before March 2010. In total, 10 studies were included in the present meta-analysis. XRCC1 haplotypes for Arg194Trp and Arg399Gln polymorphisms were included in the analysis. The association was measured using random-effect model or fixed-effect model odds ratio (OR) combined with 95% confidence intervals (CIs) according to the between studies’ heterogeneity. Large between-study heterogeneity was observed (Q = 25.587, df = 9, P < 0.001). The meta-analysis showed a borderline increased risk of breast cancer associated with the Arg194-Gln399 haplotype versus the Arg194-Arg399 haplotype (OR = 1.07, 95% CI: 1.01–1.14). There was no significant association between XRCC1 haplotypes and risk of breast cancer among Caucasoid subjects. In the next step, studies were classified according to geographical locations. Studies reported form Western populations did not show heterogeneity, and the Arg194-Gln399 haplotype was not associated with risk of breast cancer in comparison with the Arg194-Arg399 haplotype (OR = 1.02, 95% CI: 0.95–1.09). Among studies reported form Asian countries, significant heterogeneity was observed. After excluding of one study which did not show linkage disequilibrium, heterogeneity between studies decreased and haplotype Arg194-Gln399 revealed significant association with increased risk of breast cancer compared with haplotype Arg194-Arg399 (OR = 1.26, 95% CI: 1.04–1.50). There was no significant association between Trp194-Arg399 haplotype and risk of breast cancer, neither in Western nor Asian countries. The present meta-analysis has indicated that the Arg194-Gln399 haplotype of XRCC1 might be a risk factor for breast cancer in Asian countries.