Interactions between cigarette smoking and XPC-PAT genetic polymorphism enhance bladder cancer risk

: Inherited polymorphisms in the XPC gene that lead to a reduction in DNA repair capacity may increase susceptibility to bladder cancer. We investigated three polymorphisms of the XPC gene (PAT, Ala499Val and Lys939Gln) in 600 subjects with bladder cancer and in 609 healthy controls by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a Chinese Han population. Smoking was associated with a significant increase in the risk for bladder cancer (OR, 2.48; 95% CI, 1.91-3.21). The risk was greater among heavy smokers (OR, 3.09, 95% CI, 2.24-4.25) compared to light smokers (OR, 1.91, 95% CI, 1.37-2.68). In three polymorphisms of XPC, only the XPC-PAT variant genotype exhibited a significantly increased risk for bladder cancer. When the total smoking exposure-gene interaction was examined, the three polymorphisms did not exhibit any significant effect in never smokers but a significant dose-response association in light or heavy smokers. Especially, the bladder cancer risk was significantly elevated among the polymorphisms of XPC-PAT(+/-) (OR, 2.56, 95% CI, 1.56-4.21, p<0.001; OR, 3.41, 95% CI, 2.19-5.29, p<0.001) and XPC-PAT(+/+) (OR, 3. 00, 95% CI, 1.31-6.88, p=0.009; OR, 6. 78, 95% CI, 3.00-15.54, p<0.001) with either light or heavy smoking exposure, respectively. XPC-PAT polymorphisms contribute to the risk for developing bladder cancer and an elevated risk of bladder cancer was significantly associated with the gene-environment (smoking) interaction in a Chinese Han population.