XRCC1 Arg399Gln variation and leukemia susceptibility: evidence from 2,647 cases and 5,518 controls

Previous reports implicate XRCC1 Arg399Gln polymorphism as a possible risk factor for several cancers. Increasing studies have been conducted on the association of XRCC1 Arg399Gln polymorphisms with susceptibility to leukemia. However, conflicting results have been generated. The goal of the present study was to derive a more precise estimation of the relationship. Meta-analyses assessing the association of XRCC1 Arg399Gln variation with leukemia were conducted, and subgroup analyses on ethnicity and clinical types were further performed. Eligible studies were identified for the period up to February 2013. Consequently, 16 publications including 17 case-control studies with 2,647 cases and 5,518 controls were selected for analysis. The overall data indicated a significant association of XRCC1 Arg399Gln polymorphism with leukemia risk (Gln/Gln versus Arg/Arg: OR = 1.37, 95% confidence interval (CI) = 1.08-1.74; dominant model: OR = 1.23, 95%CI = 1.03-1.46; recessive model: OR = 1.23, 95%CI = 1.06-1.44). In the subgroup analysis by ethnicity, Gln allele may increase leukemia susceptibility among Asians (Gln/Gln versus Arg/Arg: OR = 1.82, 95%CI = 1.19-2.78; dominant model: OR = 1.53, 95%CI = 1.00-2.33; recessive model: OR = 1.51, 95%CI = 1.11-2.06), but not Caucasians or mixed ethnicities. In the subgroup analysis by clinical types, increased risk was observed in acute lymphocytic leukemia (ALL) subgroup (Gln/Gln versus Arg/Arg: OR = 1.45, 95%CI = 1.09-1.93; recessive model: OR = 1.30, 95%CI = 1.00-1.69), but not in acute myeloid leukemia, chronic lymphocytic leukemia, or chronic myeloid leukemia subgroups, respectively. Collectively, the results of the present study suggest that XRCC1 Arg399Gln polymorphism might be a low-penetrant risk factor for leukemia, particularly among Asians. Homozygous Gln/Gln alleles might have a correlation with increased ALL susceptibility.