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Genetic polymorphisms in NQO1 and SOD2: interactions with smoking, schistosoma infection, and bladder cancer risk in Egypt.

ABSTRACT: Bladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms inquinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer.We assessed the effects of potential interactions between functional polymorphisms in the NQO1 and SOD2 genes and exposure to smoking and SH infection on bladder cancer risk among 902 cases and 804 population-based controls in Egypt. We used unconditional logistic regression to estimate the odds ratios (OR) and confidence intervals (CI) 95%.Water pipe and cigarette smoking were more strongly associated with cancer risk among individuals with the TT genotype for SOD2 (OR [CI 95%] = 4.41 [1.86-10.42]) as compared with those with the CC genotype (OR [CI 95%] = 2.26 [0.97-6.74]). Conversely, the risk associated with SH infection was higher among the latter (OR [CI 95%] = 3.59 [2.21-5.84]) than among the former (OR [CI 95%] = 1.86 [1.33-2.60]). Polymorphisms in NQO1 genotype showed a similar pattern, but to a much lesser extent. The highest odds for having bladder cancer following SH infection were observed among individuals with the CC genotypes for both NQO1 and SOD2 (OR [CI 95%] = 4.41 [2.32-8.38]).Our findings suggest that genetic polymorphisms in NQO1 and SOD2 play important roles in the etiology of bladder cancer by modulating the effects of known contributing factors such as smoking and SH infection.

SUBMITTER: Goerlitz D

PROVIDER: S-EPMC3885358 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Genetic polymorphisms in NQO1 and SOD2: interactions with smoking, schistosoma infection, and bladder cancer risk in Egypt.

Goerlitz David D Amr Sania S Dash Chiranjeev C Saleh Doa'a A DA El Daly Mai M Abdel-Hamid Mohamed M El Kafrawy Sherif S Hifnawy Tamer T Ezzat Sameera S Abdel-Aziz Mohamed A MA Khaled Hussein H Zheng Yun-Ling YL Mikhail Nabiel N Loffredo Christopher A CA

Urologic oncology 20130910 1

<h4>Background</h4>Bladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms in<h4>Nad(p)h</h4>quinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer. ...[more]

PMID: 24035474

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Project description:BACKGROUND AND OBJECTIVE: The X-ray repair cross-complementing group 1 (XRCC1) protein plays a crucial role in base excision repair (BER) pathway by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, a comprehensive meta-analysis of all available studies was performed in this study. METHODS: PubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases have been systematically searched to identify all relevant studies for the period up to February 2013. Data were abstracted independently by two reviewers and Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed mainly by ethnicity and smoking status. RESULTS: A total of 26 case-control studies, including 24 studies for R399Q polymorphism, 15 studies for R194W polymorphism, and 7 studies for R280H polymorphism met the inclusion criteria and were selected. With respect to R399Q polymorphism, significantly decreased bladder cancer risk was found among smokers (AA vs. GG: OR=0.693, 95%CI= 0.515-0.932, P=0.015 and recessive model AA vs. GA+GG: OR=0.680, 95%CI= 0.515-0.898, P=0.007, respectively). With respect to R194W and R280H polymorphism, significantly increased bladder cancer risk were observed among Asians (TT+CT vs. CC:OR = 1.327, 95% CI 1.086-1.622, P=0.006 for R194W, and AA+GA vs. GG: OR=2.094, 95% CI 1.211-3.621, P=0.008 for R280H, respectively). CONCLUSIONS: This meta-analysis suggests that the XRCC1 R399Q polymorphism may play a protective role against bladder cancer among smokers. However, the XRCC1 R194W and R280H polymorphisms were both associated with increased bladder cancer risk among Asians. Further studies with larger sample sizes are needed to validate our finds.

Dataset Information

Genetic polymorphisms in NQO1 and SOD2: interactions with smoking, schistosoma infection, and bladder cancer risk in Egypt.

Publications

Genetic polymorphisms in NQO1 and SOD2: interactions with smoking, schistosoma infection, and bladder cancer risk in Egypt.

Similar Datasets

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