David Goerlitz1, Sania Amr2, Chiranjeev Dash1, Doa'a A Saleh3, Mai El Daly4, Mohamed Abdel-Hamid5, Sherif El Kafrawy6, Tamer Hifnawy7, Sameera Ezzat8, Mohamed A Abdel-Aziz9, Hussein Khaled10, Yun-Ling Zheng1, Nabiel Mikhail11, Christopher A Loffredo12. 1. Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC. 2. Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD. 3. Department of Public Health, Cairo University, Cairo, Egypt. 4. Department of Microbiology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; National Liver Institute, Menoufiya University, Shibin El Kom, Egypt. 5. Department of Microbiology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; Department of Microbiology, Minia University, Minia, Egypt. 6. Department of Microbiology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; National Liver Institute, Menoufiya University, Shibin El Kom, Egypt; King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. 7. Public Health Department, Beni Suif University, Beni Suif, Egypt. 8. National Liver Institute, Menoufiya University, Shibin El Kom, Egypt. 9. Department of Urology, Assiut University, Assiut, Egypt. 10. Department of Medical Oncology, National Cancer Institute, Cairo, Egypt. 11. Department of Microbiology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; Department of Urology, Assiut University, Assiut, Egypt. 12. Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC. Electronic address: cal9@georgetown.edu.
Abstract
BACKGROUND: 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 NAD(P)H: 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. METHODS: 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%. RESULTS: 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]). CONCLUSION: 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.
BACKGROUND: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 NAD(P)H: 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. METHODS: 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%. RESULTS: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]). CONCLUSION: 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.
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