X-ray repair cross-complementing group 1 (XRCC1), a DNA repair enzyme, plays a crucial role in the base excision repair by generating a single nucleotide repair patch. It has been demonstrated that the XRCC1 Arg399Gln gene polymorphism was associated with variations in XRCC1 enzyme activity. The aim of this study was to quantitatively summarize the association between the XRCC1 Arg399Gln polymorphism and susceptibility to colorectal cancer (CRC). A comprehensive search of the PubMed, Embase, and China National Knowledge Infrastructure databases was conducted for studies on the association between the XRCC1 Arg399Gln polymorphism and CRC risk. Summary odds ratio (OR) with its corresponding 95 % confidence interval (95 %CI) was estimated, in a fixed-effects model or a random-effects model when appropriate, to assess the association. Totally, 26 case-control studies with 6,979 cases and 11,470 controls were included into this meta-analysis. The pooled results of total studies showed that the XRCC1 Arg399Gln polymorphism was significantly associated with increased risk of CRC in all genetic contrast models (OR(A vs. G) = 1.13, 95 %CI 1.03-1.23, P (OR) = 0.008; OR(Gln/Gln vs. Arg/Arg) = 1.24, 95 %CI 1.04-1.46, P (OR) = 0.015; OR(Gln/Gln vs. Arg/Gln + Arg/Arg) = 1.19, 95 %CI 1.03-1.38, P (OR) = 0.021; OR(Gln/Gln + Arg/Gln vs. Arg/Arg) = 1.14, 95 %CI 1.02-1.28, P (OR) = 0.022), except for the additive contrast model (OR(Arg/Gln vs. Arg/Arg) = 1.11, 95 %CI 0.99-1.25, P (OR) = 0.064). The statistically significant association between the XRCC1 Arg399Gln polymorphism and CRC risk was observed among studies with high quality and in Asians, but not in Caucasians. Sensitivity analyses by sequential omission of any individual studies further identified the significant association. Publication bias was inexistent in this meta-analysis. The meta-analysis suggests that the XRCC1 Arg399Gln polymorphism is associated with increased risk of CRC.
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