title: Genetic polymorphisms in NQO1 and SOD2: interactions with smoking, schistosoma infection, and bladder cancer risk in Egypt.
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
  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]).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
authors.forename: David
authors.initials: D
authors.lastname: Goerlitz
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: Sania
authors.initials: S
authors.lastname: Amr
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
authors.forename: Chiranjeev
authors.initials: C
authors.lastname: Dash
authors.affiliation: Department of Public Health, Cairo University, Cairo, Egypt.
authors.forename: Doa'a A
authors.initials: DA
authors.lastname: Saleh
authors.affiliation: Department of Microbiology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; National Liver Institute, Menoufiya University, Shibin El Kom, Egypt.
authors.forename: Mai
authors.initials: M
authors.lastname: El Daly
authors.affiliation: Department of Microbiology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; Department of Microbiology, Minia University, Minia, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Hamid
authors.affiliation: 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.
authors.forename: Sherif
authors.initials: S
authors.lastname: El Kafrawy
authors.affiliation: Public Health Department, Beni Suif University, Beni Suif, Egypt.
authors.forename: Tamer
authors.initials: T
authors.lastname: Hifnawy
authors.affiliation: National Liver Institute, Menoufiya University, Shibin El Kom, Egypt.
authors.forename: Sameera
authors.initials: S
authors.lastname: Ezzat
authors.affiliation: Department of Urology, Assiut University, Assiut, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Medical Oncology, National Cancer Institute, Cairo, Egypt.
authors.forename: Hussein
authors.initials: H
authors.lastname: Khaled
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
authors.forename: Yun-Ling
authors.initials: YL
authors.lastname: Zheng
authors.affiliation: Department of Microbiology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; Department of Urology, Assiut University, Assiut, Egypt.
authors.forename: Nabiel
authors.initials: N
authors.lastname: Mikhail
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC. Electronic address: cal9@georgetown.edu.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Loffredo
mesh_terms: D000368:Aged; D000818:Animals; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006790:Host-Parasite Interactions; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012548:Schistosoma haematobium / Q000502:physiology; D012553:Schistosomiasis haematobia / Q000469:parasitology; D012907:Smoking / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000235:genetics* / Q000469:parasitology; D000099156:Superoxide Dismutase 2
chemical_list: D016660:NAD(P)H Dehydrogenase (Quinone); D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C447479:NQO1 protein, human
keywords: Bladder cancer; Epidemiology; NQO1; SOD2; Schistosomiasis; Smoking
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