Association between XRCC3 Thr241Met polymorphism and colorectal cancer risk

Abstract

The x-ray repair cross-complementing group 3 (XRCC3), a member of DNA repair genes, plays a critical role in the maintenance of genome stability by homologous recombination repair for DNA double-strand breaks. The polymorphism of XRCC3 Thr241Met has been indicated to be involved in the development of some cancers, but previous individual studies on the association between XRCC3 Thr241Met polymorphism and colorectal cancer (CRC) risk have yielded conflicting and inconclusive results. To shed some light on the contradictory findings and improve our understanding of the pathogenesis of CRC, we carried out this updated meta-analysis by pooling all available publications. Databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure were searched for relevant publications. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the strength of the association between XRCC3 Thr241Met polymorphism and CRC risk. A total of 15 case-control studies involving 4,475 cases and 6,373 controls were included. Overall, the pooled ORs for the meta-analysis of total included studies showed no statistically significant association of XRCC3 Thr241Met polymorphism with CRC risk in any genetic model (ORMet allele vs. Thr allele=1.17, 95 % CI 0.97-1.42, P OR=0.102; ORMetMet vs. ThrThr =1.32, 95 % CI 0.93-1.87, P OR=0.121; ORThrMet vs. ThrThr =1.17, 95 % CI 0.94-1.45, P OR=0.150; ORMetMet + ThrMet vs. ThrThr =1.20, 95 % CI 0.96-1.51, P OR=0.114; ORMetMet vs. ThrThr + ThrMet =1.37, 95 % CI 0.98-1.93, P OR=0.065). However, in subgroup analyses stratified by source of controls and ethnicity, the XRCC3 Thr241Met polymorphism was associated with an elevated risk of CRC in the hospital-based case-control studies and the Asian population. Sensitivity analysis indicated that the findings were unlikely due to chance. This meta-analysis suggests that the XRCC3 Thr241Met polymorphism may modify the risk of CRC, particularly in Asians.