Association between the XRCC3 Thr241Met Polymorphism and Gastrointestinal Cancer Risk: A 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;">The x-ray repair cross-complementing group 3 (XRCC3) encodes a protein involved in the homologous recombination repair (HRR) pathway for double-strand DNA repair. Associations of the XRCC3 Thr241Met polymorphism with various cancers have been widely reported. However, published data on links between XRCC3 </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;">Thr241Met and gastrointestinal (GI) cancer risk are inconsistent. </span></span><strong><span style="font-size: small;">Objective 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 meta-analysis was </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;">conducted to characterize the relationship between XRCC3 Thr241Met polymorphisms and GI cancer risk. Pooled odds ratios (ORs) and 95.0% confidence intervals were assessed using random- or fixed- effect models for 28.0 relevant </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;">articles with 30.0 studies containing 7,649.0 cases and 11,123.0 controls. </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;">The results of the overall meta-analysis </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;">suggested a borderline association between the XRCC3 Thr241Met polymorphism and GI cancer susceptibility (T vs. C: OR=1.18, 9 % CI=1.0–1.4, POR=0.04; TT vs. CT+CC: OR=1.3, 95 % CI=1.0–1.6, POR=0.04). After removing studies not conforming to Hardy–Weinberg equilibrium (HWE), however, this association disappeared (T vs. C: OR=1.00, 95 % CI=0.9–1.1, POR=0.96; TT vs. CT+CC: OR=0.9, 95 % CI=0.8–1.1, POR=0.72). When stratified by ethnicity, source of controls or cancer type, although some associations between XRCC3 Thr241Met 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;">and GI cancer susceptibility were detected, these associations no longer existed after removing studies not conforming </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;">to HWE. </span></span><strong><span style="font-size: small;">Conclusion: </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;">Our meta-analysis suggests that the XRCC3 Thr241Met polymorphism is not associated with </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 GI cancer based on current evidence. </span></span>