Genetic variants of XRCC1, APE1, and ADPRT genes and risk of bladder cancer.

DNA damaged by exposure to exogenous and endogenous carcinogens could be removed effectively by the base excision repair pathway, in which the XRCC1, APE1, and ADPRT genes play a key role. Genetic variations in these important genes may alter repair function and contribute to cancer risk. We hypothesized that XRCC1, APE1, and ADPRT polymorphisms are associated with risk of bladder cancer. In a hospital-based case-control study of 234 patients with bladder cancer and 253 cancer-free controls, we genotyped the XRCC1-77T>C, Arg194Trp, Arg280His, Arg399Gln, APE1-656T>G, Asp148Glu, ADPRT-442G>A, and Val762Ala polymorphisms using polymerase chain reaction-restriction fragment length polymorphism method. We found an increased risk of bladder cancer associated with the XRCC1 194Trp/Trp and 280Arg/His genotypes (adjusted odds ratio = 3.90, 95% confidence interval = 1.69-8.98 for 194Trp/Trp and 2.53, 1.67-3.83 for 280Arg/His) compared with the 194Arg/Arg and 280Arg/Arg genotypes, respectively. In contrast, the APE1-656GG genotype was associated with a decreased risk of bladder cancer (0.57, 0.33-0.98) compared with the TT genotype. When we evaluated these eight polymorphisms together, we found that the combined genotypes with 9-13 variant (risk) alleles were associated with an increased risk of bladder cancer (2.25, 1.48-3.40) compared with those with 3-8 variants. These findings suggest that the XRCC1 and APE1 polymorphisms may contribute to susceptibility to bladder cancer. Larger studies are warranted to verify these findings.

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