Association between the XRCC1 Arg399Gln polymorphism and risk of cancer: evidence from 297 case-control studies.

Background: The Arg399Gln polymorphism in the X-ray cross-complementing group 1 (XRCC1) had been implicated in cancer susceptibility. The previous published data on the association between XRCC1 Arg399Gln polymorphism and cancer risk remained controversial.

Methodology/principal Findings: To derive a more precise estimation of the association between the XRCC1 Arg399Gln polymorphism and overall cancer risk, we performed a meta-analysis of 297 case-control studies, in which a total of 93,941 cases and 121,480 controls were included. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ration [OR] = 1.04, 95% confidence interval [CI] = 1.01-1.07; recessive model: OR = 1.08, 95% CI = 1.03-1.13; additive model: OR = 1.09, 95% CI = 1.04-1.14) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, significantly elevated hepatocellular and breast cancers risk were observed in Asians (dominant model: OR = 1.39, 95% CI = 1.06-1.84) and in Indians (dominant model: OR = 1.64, 95% CI = 1.31-2.04; recessive model: OR = 1.94, 95% CI = 1.09-3.47; additive model: OR = 2.06, 95% CI = 1.50-2.84), respectively.

Conclusions/significance: This meta-analysis suggests the participation of XRCC1 Arg399Gln is a genetic susceptibility for hepatocellular cancer in Asians and breast cancer in Indians. Moreover, our work also points out the importance of new studies for Arg399Gln association in some cancer types, such as glioma, gastric cancer, and oral cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC1 Arg399Gln polymorphism in cancer development.