Complex association between ERCC2 gene polymorphisms, gender, smoking and the susceptibility to bladder cancer: a...

Genetic polymorphisms in DNA repair genes may be involved in increasing the risk of bladder cancer. Association studies on the excision repair cross-complementation group 2 (ERCC2) gene polymorphisms and bladder cancer risk have reported conflicting results. The aim of this meta-analysis of eligible cancer case-control studies is to investigate the role of ERCC2 SNPs (Arg156Arg, Asp312Asn, and Lys751Gln), gender and smoking in determining susceptibility to bladder cancer. A literature search was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases to indentify eligible studies published before December 1, 2013. We performed a meta-analysis of 23 case-control studies with a total of 7,062 bladder cancer patients and 8,832 controls. The overall analysis suggested that ERCC2 Arg156Arg, Asp312Asn, and Lys751Gln are associated with increased bladder cancer risk. For ERCC2 Arg156Arg, the mutant allele was associated with a 1.36-fold (95 % CI=1.15-1.61) increased risk of bladder cancer. For ERCC2 Asp312Asn, individuals with the Asn allele were associated with a 1.29-fold (95 % CI=1.13-1.48) increased risk of bladder cancer. For ERCC2 Lys751Gln, individuals who carried the variant heterozygote Lys/Gln or homozygote Gln/Gln had a significantly increased bladder cancer risk, compared with the wild genotype Lys/Lys (OR=1.10, 95 % CI=1.03-1.18). Furthermore, gender and smoking may modify the association between these SNPs and bladder cancer risk. This study provides the strongest evidence to date for the role of common variants of the ERCC2 gene in bladder carcinogenesis. Further studies comprehensively characterizing other DNA repair pathways and accounting for exposure to relevant environmental factors should offer further insight into the role of DNA repair in bladder cancer.