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

Abstract

<br /> <strong><span style="font-size: small;">Background: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">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. </span></span><strong><span style="font-size: small;">Materials and Methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">A systematic literature search </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">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. </span></span><strong><span style="font-size: small;">Results: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">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, </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">significantly increased TC risk was observed only in Asians under the recessive model (TT vs. TC+CC: OR = 1.816, </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">95% CI = 1.398-2.358, p= <0.001). In addition, there was no positive association between XRCC1 rs25487 and rs25489 </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">polymorphisms and risk of TC. However, there was a significant association between XRCC1 rs25487 polymorphism </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">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). </span></span><strong><span style="font-size: small;">Conclusions: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">The results of our meta-analysis suggest an increased risk of TC with the XRCC1 rs1799782 and rs25487 polymorphisms. </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">However, the XRCC1 rs25489 polymorphism appeared to be without influence. </span></span>