Genetic Association of XRCC1 Gene rs1799782, rs25487 and rs25489 Polymorphisms with Risk of Thyroid Cancer: a Systematic Review and Meta-Analysis

Background: A number of case-control studies have evaluated associations between the X-ray cross complementary group 1 protein (XRCC1) gene rs1799782 (Arg194Trp), rs25487 (Arg399Gln) and rs25489 (Arg280His) polymorphisms and thyroid cancer (TC) risk, but the results remain inconclusive. Materials and Methods: A systematic literature search was performed using PubMed and Google Scholar Search. According to defined criteria data were extracted and pooled odds ratios with 95% confidence intervals were calculated under five genetic models. Results: A total of 8 studies with 1,672 cases and 2,805 controls for the rs1799782 polymorphism, 14 studies with 2,506 cases and 5,180 controls for the rs25487 polymorphism, and 11 studies with 2,197 cases and 4,761 controls for the rs25489 polymorphism were included in this meta-analysis. Overall, there was a statistical association between XRCC1 rs1799782 polymorphism and TC risk with the homozygote genetic model (TT vs. CC: OR = 1.815, 95% CI = 1.115-2.953, p= 0.016) and the recessive genetic model (TT vs. TC+CC: OR = 1.854, 95% CI = 1.433-2.399, p= <0.001). In the subgroup analysis by ethnicity, significantly increased TC risk was observed only in Asians under the recessive model (TT vs. TC+CC: OR = 1.816, 95% CI = 1.398-2.358, p= <0.001). In addition, there was no positive association between XRCC1 rs25487 and rs25489 polymorphisms and risk of TC. However, there was a significant association between XRCC1 rs25487 polymorphism risk of TC among Caucasians with allele genetic comparison (A vs. G: OR= 0.882, 95% CI = 0.794-0.979, p= 0.136) and dominant genetic comparison (AA+AG vs. GG: OR=0.838, 95% CI = 0.728-0.965, p= 0.014). Conclusions: The results of our meta-analysis suggest an increased risk of TC with the XRCC1 rs1799782 and rs25487 polymorphisms. However, the XRCC1 rs25489 polymorphism appeared to be without influence.