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

Abstract

BackgroundNAD(P)H:quinone oxidoreductase 1 (NQO1), an obligate two-electron reductase, plays an important role in reducing reactive quinones to less reactive and less toxic hydroquinones. Genetic variations in NQO1 gene that impede its enzyme function may be considered as putative risk factor for cancer. Numerous studies have been performed to investigate the association between NQO1 Pro187Ser polymorphism and bladder cancer risk; nevertheless, the results remain controversial.MethodsWe indentified eligible publications from PubMed, Embase and CBM databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to access the strength of the associations. False-positive report probability (FPRP) analysis was also performed for all statistically significant findings.ResultsWe collected a total of 15 studies including 4298 cases and 4275 controls in the final meta-analysis. Overall, the NQO1 187Ser carriers were associated with an increased bladder cancer risk (homozygous: OR = 1.43, 95% CI = 1.08-1.90; recessive: OR = 1.33, 95% CI = 1.03-1.72; dominant: OR = 1.19, 95% CI = 1.04-1.37, and allele comparing: OR = 1.18, 95% CI = 1.06-1.33). Stratification analyses showed a statistically significant association among Asians (homozygous: OR = 1.82, 95% CI = 1.39-2.38; recessive: OR = 1.52, 95% CI = 1.20-1.93, dominant: OR = 1.40, 95% CI = 1.05-1.88, and allele comparing: OR = 1.35, 95% CI = 1.15-1.58), never smokers (homozygous: OR = 2.30, 95% CI = 1.14-4.65; heterozygous: OR = 2.26, 95% CI = 1.43-3.56; dominant model: OR = 1.59, 95% CI = 1.14-2.21, and allele comparing: OR = 1.72, 95% CI = 1.27-2.33), hospital-based studies (homozygous: OR = 1.46, 95% CI = 1.09-1.94; recessive: OR = 1.32, 95% CI = 1.02-1.69; dominant: OR = 1.28, 95% CI = 1.05-1.56, and allele comparing: OR = 1.24, 95% CI = 1.07-1.43), studies with genotyping performed by PCR-RFLP under all genetic models, and studies with minor allele frequency >0.30 (homozygous: OR = 1.69, 95% CI = 1.25-2.27; recessive: OR = 1.46, 95% CI = 1.10-1.95, and allele comparing: OR = 1.25, 95% CI = 1.04-1.51), respectively.ConclusionsDespite some limitations, our meta-analysis provides sufficient evidence that NQO1 Pro187Ser polymorphism may contribute to bladder cancer risk. These findings need further validation in well-designed prospective studies with larger sample size and different ethnicities, especially for Asians.

Association between interleukin-22 genetic polymorphisms and bladder cancer risk

“…There is accumulating evidence that genetics plays a key role in the susceptibility to and clinicopathologic characteristics of bladder cancer. Nine meta-analyses, each of which analyzed between four and twenty-four studies, have provided evidence that the following polymorphisms are associated with increased bladder cancer risk: NQO1 Pro187Ser; PSCA rs2294008 (C>T); XRCC1 Arg399Gln (especially in non-Asian populations); MMP-2 -1306 C/T; MMP-9 -1562 C/T; XPD Lys751Gln; ERCC2 Arg156Arg; Asp312Asn; Lys751Gln; CCND1 G870A (which may modulate the risk of bladder cancer in conjunction with tobacco smoking); XPC A499V (in Caucasian populations); CYP1A1 polymorphisms (especially the 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms in Asians); MDM2 SNP309T>G (among Caucasians) 28 - 36 .…”

Alzheimer's Disease and NQO1: Is there a Link?

“…Heterozygote carriers (C/T) only show about 50% NQO1 activity compared to carriers of the C/C genotype and homozygote carriers (T/T) only harbour very low to undetectable residual activity [95,96]. The NQO1*2 polymorphism has been associated with several pathological conditions and disorders [86,[97][98][99][100].…”

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.…”