Association Of XRCC1Polymorphisms And Glioma Risk: A Meta-Analysis

Background and Objective: X-ray repair cross-complementing gene1(XRCC1), oneof the most important DNA repair genes, plays a key role in the process of base excisionrepair. Three single nucleotide polymorphisms of XRCC1, namely, Arg399Gln, Arg194Trpand Arg280His, have been widely studied. Previous reports implicate XRCC1polymorphismsas possible risk factors for several cancers. Published data on the association of XRCC1polymorphisms with glioma susceptibility have generated conflicting results. The presentstudy aimed to derive a more precise estimation of the relationship.Methods: A search in the Medline, EMBASE, OVID, Sciencedirect, and ChineseNational Knowledge Infrastructure (CNKI), covering all papers published up to May2012,was performed to find relevant studies. Two investigators independently performed the samesearch and study selection. Meta-analyses were then performed for the selected studies usingSTATA11.0software (Stata Corporation, Texas) after strict screening. Subgroup analysis onethnicity and source of controls were also conducted. Heterogeneity tests, sensitivity analysesand publication bias assessments were then performed.Results:(1) For Arg399Gln, a total of nine case-control studies comprising2326casesand3610controls were lastly selected for analysis. The overall data failed to indicate asignificant association of XRCC1Arg399Gln polymorphism with glioma risk (Gln vs Arg：OR=1.04;95%CI=0.92-1.18; Gln/Gln vs Arg/Arg: OR=1.11;95%CI=0.94-1.31; dominantmodel: OR=1.06;95%CI=0.95-1.18; recessive model: OR=1.04;95%CI=0.81-1.34). However,subgroup analysis regarding ethnicity showed an increased risk among Asians (Gln vs Arg：OR=1.34;95%CI=1.12-1.60; Gln/Gln vs Arg/Arg: OR=1.70;95%CI=1.17-2.46; dominantmodel: OR=1.40;95%CI=1.10-1.78; recessive model: OR=1.46;95%CI=1.04-2.05) but notCaucasians or mixed ethnicities.(2) For Arg194Trp, a total of four case-control studies comprising1440cases and2562controls were lastly selected for analysis. The overall data failed to indicate a significant association of XRCC1Arg194Trp polymorphism with glioma risk (Trp vs Arg: OR=1.01;95%CI=0.77-1.33; Trp/Trp vs Arg/Arg: OR=1.56;95%CI=0.96-2.54; dominant model:OR=0.98;95%CI=0.74-1.31; recessive model: OR=1.48;95%CI=0.92-2.38). Likewise, in thesubgroup analysis regarding ethnicity and source of controls, no associations could beobserved.(3) For Arg280His, four case-control studies comprising1439cases and2564controlswere lastly selected for analysis. The overall data indicated no significant association ofXRCC1Arg280His polymorphism with glioma risk (His vs Arg: OR=1.05;95%CI=0.88-1.25;His/His vs Arg/Arg: OR=1.42;95%CI=0.87-2.29; dominant model: OR=1.00;95%CI=0.82-1.22; recessive model: OR=1.41;95%CI=0.88-2.25). Likewise, in the subgroup analysisregarding ethnicity and source of controls, no associations were observed.Conclusion: The results of the present study suggest that XRCC1Arg399Glnpolymorphism might modify the susceptibility to glioma among Asians but not Caucasians.For XRCC1Arg194Trp and Arg280His, the data indicate that they are not likely to be riskfactors for glioma. Further large and well-designed studies are needed to get more conclusiveresults.