Association between X-ray repair cross-complementing group 1 Arg194Trp polymorphism and colorectal cancer risk

The polymorphism of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, a substitution of Arg to Gln at position 194, has been implicated in the development of colorectal cancer (CRC) in a number of case-control studies with contradictory and inconclusive findings. The current meta-analysis of all currently available publications was conducted to assess the gene susceptibility to CRC and improve our understanding of the CRC pathogenesis. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated by use of fixed-effects model or random-effects model when appropriate. A total of 15 eligible case-control studies with 4,501 cases and 8,038 controls were retrieved after a comprehensive search of the PubMed, Embase, Web of science, and Chinese Biomedicine (CBM) databases up to December 2012. The overall meta-analysis identified a positive but not statistically significant association between the XRCC1 Arg194Trp polymorphism and CRC risk under all genetic contrast models (ORTrp vs. Arg = 1.07, 95 % CI 0.90-1.26, P OR = 0.441; ORTrpTrp vs. ArgArg = 1.28, 95 % CI 0.91-1.81, P OR = 0.163; ORArgTrp vs. ArgArg = 1.00, 95 % CI 0.85-1.19, P OR = 0.956; ORArgTrp + TrpTrp vs. ArgArg = 1.06, 95 % CI 0.90-1.24, P OR = 0.502; ORTrpTrp vs. ArgArg + ArgTrp = 1.11, 95 % CI 0.91-1.34, P OR = 0.306). The genotype TrpTrp carriers among Caucasians were more susceptible to CRC, although lack statistical evidence (ORTrpTrp vs. ArgArg = 2.69, 95 % CI 0.97-7.49, P OR = 0.058; ORTrpTrp vs. ArgArg + ArgTrp = 2.77, 95 % CI 0.99-7.72, P OR = 0.051). Interestingly, the XRCC1 Arg194Trp variant was significantly associated with an increased risk of colon cancer. The present meta-analysis suggests that the XRCC1 Arg194Trp polymorphism may modify the risk for CRC, particularly colon cancer. However, the precise genetic association needs to be further estimated in future studies.