The Relationship between Seven Common Polymorphisms from Five DNA Repair Genes and the Risk for Breast Cancer in Northern Chinese Women

Abstract

BackgroundConverging evidence supports the central role of DNA damage in progression to breast cancer. We therefore in this study aimed to assess the potential interactions of seven common polymorphisms from five DNA repair genes (XRCC1, XRCC2, XRCC3, XPA and APEX1) in association with breast cancer among Han Chinese women.Methodology/Principal FindingsThis was a case-control study involving 606 patients diagnosed with sporadic breast cancer and 633 age- and ethnicity-matched cancer-free controls. The polymerase chain reaction - ligase detection reaction method was used to determine genotypes. All seven polymorphisms were in accordance with Hardy-Weinberg equilibrium in controls. Differences in the genotypes and alleles of XRCC1 gene rs25487 and XPA gene rs1800975 were statistically significant between patients and controls, even after the Bonferroni correction (P<0.05/7). Accordingly, the risk for breast cancer was remarkably increased for rs25487 (OR = 1.28; 95% CI: 1.07–1.51; P = 0.006), but decreased for rs1800975 (OR = 0.77; 95% CI: 0.67–0.90; P = 0.001) under an additive model at a Bonferroni corrected alpha of 0.05/7. Allele combination analysis showed higher frequencies of the most common combination C-G-G-C-G-G-G (alleles in order of rs1799782, rs25487, rs3218536, rs861539, rs1800975, rs1760944 and rs1130409) in controls than in patients (PSim = 0.002). In further interaction analysis, two-locus model including rs1800975 and rs25487 was deemed as the overall best model with the maximal testing accuracy of 0.654 and the cross-validation consistency of 10 out of 10 (P = 0.001).ConclusionOur findings provide clear evidence that XRCC1 gene rs25487 and XPA gene rs1800975 might exert both independent and interactive effects on the development of breast cancer among northern Chinese women.