Association between NQO1 C609T polymorphism and bladder cancer susceptibility: a systemic review and meta-analysis

There is growing evidence for the important roles of genetic factors in the host's susceptibility to bladder cancer. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reduction of quinoid compounds into hydroquinones. Since the NQO1 C609T polymorphism is linked to enzymatic activity of NQO1, it has also been hypothesized that NQO1 C609T polymorphism may affect the host's susceptibility to bladder cancer by modifying the exposure to carcinogens. There were many studies carried out to assess the association between NQO1 C609T polymorphism and bladder cancer risk, but they reported contradictory results. We conducted a meta-analysis to examine the hypotheses that the NQO1 C609T polymorphism modifies the risk of bladder cancer. Eleven case-control studies with 2,937 bladder cancer cases and 3,008 controls were included in the meta-analysis. Overall, there was no obvious association between NQO1 C609T polymorphism and bladder cancer susceptibility (for T versus C: odds ratio (OR) = 1.12, 95 % confidence interval (95 %CI) 0.99-1.26, P OR = 0.069; for TT versus CC: OR = 1.31, 95 %CI 0.95-1.81, P OR = 0.100; for TT/CT versus CC: OR = 1.06, 95 %CI 0.95-1.18, P OR = 0.304; for TT versus CT/CC: OR = 1.29, 95 %CI 0.94-1.77, P OR = 0.112). After adjusting for heterogeneity, meta-analysis of those left 10 studies showed that there was an obvious association between NQO1 C609T polymorphism and bladder cancer susceptibility (for T versus C: OR = 1.18, 95 %CI 1.06-1.31, P OR = 0.003; for TT versus CC: OR = 1.47, 95 %CI 1.14-1.90, P OR = 0.003; for TT/CT versus CC: OR = 1.16, 95 %CI 1.01-1.34, P OR = 0.036; for TT versus CT/CC: OR = 1.39, 95 %CI 1.10-1.75, P OR = 0.006). There was low risk of publication bias. Therefore, our meta-analysis suggests that NQO1 C609T polymorphism is associated with bladder cancer susceptibility.