XPD polymorphisms, cigarette smoking, and bladder cancer risk: a meta-analysis

Genetic polymorphisms in DNA repair genes may be involved in increased risk for bladder cancer. Association studies on the XPD Asp312Asn and Lys751Gln polymorphisms with bladder cancer development reported conflicting results. A meta-analysis from eligible cancer case-control studies was performed to assess potential associations. In total, eight studies were used with a fixed effects model or a random effects model to estimate the odds ratio (OR) for XPD polymorphisms and occurrence of bladder cancer. The overall risk for the variant homozygote Asn/Asn and genotype (Asp/Asn + Asn/Asn) of Asp312Asn polymorphism showed a significant correlation with increased bladder cancer occurrence compared to wild genotype Asp/Asp (OR = 1.23, 95% CI = 1.02-1.49 for Asn/Asn vs. Asp/Asp; OR = 1.14, 95% CI = 1.01-1.28 for Asp/Asn + Asn/Asn vs. Asp/Asp). In contrast, no significant association with elevated risk of bladder cancer was found for Lys751Gln polymorphism. In the stratification analysis, there was no significant association between increased risk of bladder cancer in the XPD polymorphisms among Caucasians. Similarly, XPD polymorphisms did not show a significant increased risk among never-smokers or ever-smokers. This meta-analysis suggested that the XPD Asp312Asn but not Lys751Gln polymorphism may be more genetically susceptible to bladder cancer development. Further studies based on larger populations and gene-environment interactions are needed to determine the role of XPD polymorphisms in bladder cancer risk.