Genetic variants of the XRCC7 gene involved in DNA repair and risk of human bladder cancer

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Abstract
Objective: To investigate the association between the polymorphisms of the KU70 and X‐ray repair cross complementing group 7 (XRCC7) genes and the risk of bladder cancer. Methods: This hospital‐based case‐control study included 213 patients with newly diagnosed bladder transitional cell carcinoma and 235 cancer‐free controls frequency‐matched by age and sex. Two polymorphisms, KU70 and XRCC7, using a method involving polymerase chain reaction‐restriction fragment length polymorphism were genotyped. Results: The risk of bladder cancer decreased in a dose–response manner as the number of XRCC76721G alleles increased (adjusted odds ratio [OR] = 0.70, 95% confident interval [CI] = 0.47–1.03 for 6721GT and OR = 0.31, 95% CI = 0.10–0.99 for 6721GG; Ptrend = 0.013). However, when we used 6721 (GT + GG) as the reference, we found a statistically significant increased risk of bladder cancer associated with the 6721TT genotype (OR = 1.53, 95% CI = 1.04–2.25). In the stratification analysis, this increased risk was more pronounced among subgroups of patients aged >65 years (OR = 2.27; 95% CI = 1.25–4.10) and ever smokers (OR = 2.06, 95% CI = 1.15–3.68). Furthermore, we observed a 3.24‐fold increased risk (95% CI = 1.35–7.78) for smokers aged >65 years carrying 6721TT genotype compared with those carrying the 6721 (GG + GT) genotype. However, the KU70−61C > G polymorphism was not associated with a significantly increased risk of bladder cancer. Conclusions: The XRCC7 but not the KU70 polymorphism appears to be involved in the etiology of human bladder cancer. Larger studies with more detailed data on environmental exposure are needed to verify these initial findings.