Association between the XRCC3 Thr241Met Polymorphism and Gastrointestinal Cancer Risk: A Meta-Analysis

Background: 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 Thr241Met and gastrointestinal (GI) cancer risk are inconsistent. Objective and Methods: A meta-analysis was 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 articles with 30.0 studies containing 7,649.0 cases and 11,123.0 controls. Results: The results of the overall meta-analysis 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 and GI cancer susceptibility were detected, these associations no longer existed after removing studies not conforming to HWE. Conclusion: Our meta-analysis suggests that the XRCC3 Thr241Met polymorphism is not associated with risk of GI cancer based on current evidence.