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NQO1 C609T polymorphism and colorectal cancer susceptibility: a meta-analysis.

ABSTRACT: INTRODUCTION:A FEW STUDIES HAVE REPORTED AN ASSOCIATION BETWEEN NADP(H): quinine oxidoreductase 1 (NQO1) C609T polymorphism and susceptibility to colorectal cancer (CRC). However, the results were inconsistent rather than conclusive. We performed a meta-analysis to examine this association in various populations. MATERIAL AND METHODS:Eligible articles were identified by a search of several databases up until June 30, 2013. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association. RESULTS:Overall, 14 case-control studies with 4,461 cases and 5,474 controls were included in this meta-analysis. The results indicated that the NQO1 C609T polymorphism was significantly associated with CRC susceptibility (summary ORs (95% CIs): 1.30 (1.07-1.59) for CT vs. CC, 1.64 (1.15-2.33) for TT vs. CC, 1.34 (1.10-1.64) for TT/CT vs. CC, and 1.43 (1.10-1.87) for TT vs. CT/CC). Subgroup analyses indicated that the T allele was significantly associated with CRC susceptibility in both Asians and Caucasians, and was also observed in high quality studies and hospital-based case-control studies. Specifically, we found a positive association between the NQO1 C609T polymorphism and CRC susceptibility in smokers, but not in non-smokers. CONCLUSIONS:The results of this meta-analysis suggest that the NQO1 C609T polymorphism significantly contributes to increased susceptibility to CRC in both Asians and Caucasians.

SUBMITTER: Zheng B

PROVIDER: S-EPMC4175766 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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NQO1 C609T polymorphism and colorectal cancer susceptibility: a meta-analysis.

Zheng Bo'an B Wang Zishu Z Chai Rui R

Archives of medical science : AMS 20140801 4

<h4>Introduction</h4>A FEW STUDIES HAVE REPORTED AN ASSOCIATION BETWEEN NADP(H): quinine oxidoreductase 1 (NQO1) C609T polymorphism and susceptibility to colorectal cancer (CRC). However, the results were inconsistent rather than conclusive. We performed a meta-analysis to examine this association in various populations.<h4>Material and methods</h4>Eligible articles were identified by a search of several databases up until June 30, 2013. Summary odds ratios (ORs) and 95% confidence intervals (CI ...[more]

PMID: 25276147

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Project description:Background nad(p)hquinone oxidoreductase 1 (NQO1) plays a central role in catalyzing the two-electron reduction of quinoid compounds into hydroquinones. The NQO1 Pro187Ser polymorphism was found to correlate with a lower enzymatic activity, which may result in increased incidence of carcinomas including breast cancer. Previous studies investigating the association between NQO1 Pro187Ser polymorphism and breast cancer risk showed inconsistent results. We performed a meta-analysis to summarize the possible association.MethodsAll studies published from January 1966 to February 2014 on the association between NQO1 Pro187Ser polymorphism and breast cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between NQO1 Pro187Ser polymorphism and breast cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).ResultsTen studies with 2,773 cases and 4,076 controls were finally included in the meta-analysis. We did not observe a significant association between NQO1 Pro187Ser polymorphism and breast cancer risk when all studies were pooled into the meta-analysis. In subgroup analysis by ethnicity, significant increased breast cancer risk was found in Caucasians (Ser/Pro vs. Pro/Pro: OR=1.145, 95% CI=1.008-1.301, P=0.038; Ser/Ser+Ser/Pro vs. Pro/Pro: OR=1.177, 95% CI=1.041-1.331, P=0.009). When stratified by source of control, significant increased breast cancer risk was found in population-based studies (Ser/Pro vs. Pro/Pro: OR=1.180, 95% CI=1.035-1.344, P=0.013; Ser/Ser+Ser/Pro vs. Pro/Pro: OR=1.191, 95% CI=1.050-1.350, P=0.007). However, in subgroup analyses according to menopausal status, quality score, and HWE in controls, no any significant association was detected.ConclusionsOur meta-analysis provides the evidence that the NQO1 Pro187Ser polymorphism contributed to the breast cancer susceptibility among Caucasians. Further large and well-designed studies are needed to confirm this association.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1248639991252504.

Project description:BackgroundNad(p)hquinone 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.

Dataset Information

NQO1 C609T polymorphism and colorectal cancer susceptibility: a meta-analysis.

Publications

NQO1 C609T polymorphism and colorectal cancer susceptibility: a meta-analysis.

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