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

Abstract

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.

Combined effects of NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism and smoking on bladder cancer risk: Two meta-analyses

“…Furthermore, great numbers of association studies have been conducted to explore the relationship between NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism and the risk of BC. Moreover, the increased effects of NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism on the risk of various cancers including BC have been clarified by the previous meta-analyses [14][15][16][17][18][19][20]. Importantly, a certain amount of the original study has not only investigated the individual effect of NQO1 Pro187Ser or SULT1A1 Arg213His on the risk of BC but has also examined the genetic effect of NQO1 Pro187Ser or SULT1A1 Arg213His modified by smoking on BC risk.…”

The Association between NQO1 Pro187Ser Polymorphism and Bladder Cancer Susceptibility: A Meta-Analysis of 15 Studies

“…The study carried out by Zhang et al [ 43 ], including nine publications with 2661 cases and 2738 controls, observed no association under all genetics models. Similarly, Gong et al also failed to detect any association, while analyzing 11 studies with 2937 cases and 3008 controls [ 44 ]. A meta-analysis by Lajin et al [ 45 ], pertaining to all types of cancer, observed a significantly increased overall cancer risk with variant Ser/Ser genotype, as compared to the homozygous wild type (Pro/Pro).…”

The MMP-1, MMP-2, and MMP-9 gene polymorphisms and susceptibility to bladder cancer: a meta-analysis

“…There is growing evidence for the important roles of genetic factors in the host’s susceptibility to bladder cancer [30–32]. Currently, there are several genetic polymorphisms which have been identified as risk factors of bladder cancer, such as cyclin D1 (CCND1) G870A polymorphism [10] and NQO1 C609T polymorphism [33]. There were a series of studies that have looked into the association between the MMP polymorphisms and bladder cancer susceptibility; however, the results obtained were inconsistent or controversial [13, 19–23].…”