The Arg194Trp and Arg399Gln polymorphisms are the most well characterized XRCC1 polymorphisms, but the reported associations with bladder cancer risk among studies are inconsistent. Our present meta-analysis incorporating 20 case–control studies suggests that the Arg194Trp and Arg399Gln polymorphisms are significantly associated with increased bladder cancer risk.
In this meta-analysis, publication bias was not observed. And there was no obvious heterogeneity between studies. In addition, when repeating the meta-analysis by omitting each study, one at a time, the estimated pooled OR still did not change at all. In view of these findings, we are convinced that the results of our meta-analysis, in essence, are sound and reliable.
The results of the present study are in contrast with a previous meta-analysis published in 2008 , which concluded that there was no association between the XRCC1 polymorphisms and the risk for bladder cancer. However, this study only included ten studies with limited sample size (3,749 cases and 3,947 controls) and, thus, it may lack sufficient statistical power to detect the real association and may have generated a fluctuated risk estimate.
Our findings have some biological plausibility. It is widely accepted that certain genetic variants associated with repair of DNA substantially increase the risk of cancer in carriers because of the alteration of BER functions . BER is the primary DNA damage repair pathway for the repairing of small base lesions resulting from oxidation and alkylation damage . As one of the most important proteins in BER, XRCC1 is closely related to BER pathway coordination by interacting with most members of the BER short-patch pathway. SNP of XRCC1 may increase the risk of some types of cancer by damaging the interaction of XRCC1 with other enzymatic proteins and, consequently, altering DNA repair activity ; this may result in carcinogenesis, including a higher incidence of bladder cancer. Similar to the results of our study, XRCC1 polymorphisms are also reported to be associated with some other cancers. The previous three meta-analyses have confirmed that the Arg399Gln polymorphism is associated with risk of childhood acute lymphoblastic leukemia , breast cancer , and prostate cancer among Asians . Dai et al. reported that the XRCC1 Arg194Trp polymorphism is associated with an increased lung cancer risk  and the study conducted by Li et al. suggested that the Arg194Trp polymorphism may be associated with cervical cancer risk . By contrast, in our study, the Arg194Trp polymorphism was associated with disease risk only in Asians, but not in Caucasians. This is mainly because the number of Caucasians is four-fold higher than that of Asians and, therefore, the power to detect association is higher.
Several limitations of this meta-analysis should be mentioned. First, the eligibility criteria for the inclusion of subjects and sources of controls were different from each other. No guarantee could be made among all those eligible studies that there were no potential bladder cancer cases in the controls. Second, because of the lack of the individual original data, our results were just based on unadjusted estimates, and gene–gene and gene–environmental interactions were not addressed in this meta-analysis. Third, although the Begg’s test and Egger’s test did not reveal any evidence of obvious publication bias, some inevitable publication bias may exist, because only studies published in English and Chinese were included in our meta-analysis. Finally, as shown in Table 3, a borderline conclusion (OR: 1.08 (1.00 to 1.18)) of the Arg399Gln section was drawn when two studies without HWE were excluded. This conclusion actually owed much to one study  with a relatively large population weight, which implies the need for more well-designed studies in future.