Goerlitz David, Amr Sania, Dash Chiranjeev, Saleh Doa'a A, El Daly Mai, Abdel-Hamid Mohamed, El Kafrawy Sherif, Hifnawy Tamer, Ezzat Sameera, Abdel-Aziz Mohamed A, Khaled Hussein, Zheng Yun-Ling, Mikhail Nabiel, Loffredo Christopher A
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD.
Urol Oncol. 2014 Jan;32(1):47.e15-20. doi: 10.1016/j.urolonc.2013.06.016. Epub 2013 Sep 10.
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.
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.
在埃及男性中，膀胱癌是最常见的癌症形式，吸烟和埃及血吸虫（SH）感染是主要危险因素。我们假设，作为活性氧化物质效应调节剂的NAD（P）H：醌氧化还原酶1（NQO1）和超氧化物歧化酶2（SOD2）中的功能多态性，会影响个体对这些致癌暴露的易感性，进而影响患膀胱癌的风险。
我们评估了埃及902例膀胱癌患者和804例基于人群的对照中，NQO1和SOD2基因功能多态性与吸烟及SH感染之间潜在相互作用对膀胱癌风险的影响。我们使用无条件逻辑回归来估计比值比（OR）和95%置信区间（CI）。
与CC基因型个体（OR [CI 95%] = 2.26 [0.97 - 6.74]）相比，SOD2基因TT基因型个体中，水烟和香烟吸烟与癌症风险的关联更强（OR [CI 95%] = 4.41 [1.86 - 10.42]）。相反，SH感染在CC基因型个体中相关风险更高（OR [CI 95%] = 3.59 [2.21 - 5.84]），高于TT基因型个体（OR [CI 95%] = 1.86 [1.33 - 2.60]）。NQO1基因型多态性表现出类似模式，但程度小得多。在NQO1和SOD2基因均为CC基因型的个体中，SH感染后患膀胱癌的几率最高（OR [CI 95%] = 4.41 [2.32 - 8.38]）。
我们的研究结果表明，NQO1和SOD2基因的遗传多态性通过调节吸烟和SH感染等已知致病因素的作用，在膀胱癌病因学中发挥重要作用。
