Park Seun-Ja, Zhao Hua, Spitz Margaret R, Grossman H Barton, Wu Xifeng
Department of Epidemiology, Unit 189, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Mutat Res. 2003 Apr 20;536(1-2):131-7. doi: 10.1016/s1383-5718(03)00041-x.
NAD(P)H:quinone oxidoreductase (NQO1) is a detoxification enzyme that plays a critical role in protecting cells against chemically induced oxidative stress, cytotoxicity, mutagenicity, and carcinogenicity. NQO1 protects cells from oxidative damage by preventing the generation of reactive oxygen species and reducing certain environmental carcinogens, such as nitroaromatic compounds, heterocyclic amines, and possible cigarette smoke condensate. A C-->T single nucleotide polymorphism in exon 6 was shown to reduce NQO1 enzyme activity, which may diminish the protection provided by NQO1. Therefore, we hypothesized that people with the variant allele genotypes of NQO1 are at higher risk for bladder cancer. In an ongoing case-control study, the NQO1 genotypes were successfully identified by polymerase chain reaction restriction fragment length polymorphism in 265 bladder cancer patients and 261 control subjects matched for age, sex, and ethnicity. The frequency of the variant NQO1 allele was 18% for controls and 21% for cases. The variant allele genotypes of NQO1 were associated with a higher risk of bladder cancer in Caucasians (odds ratio (OR)=1.51; 95% confidence interval (CI)=1.01-2.25). Further analysis in Caucasians showed an elevated bladder cancer risk in men (OR=1.75; 95% CI=1.08-2.85) but not in women (OR=1.16; 95% CI=0.57-2.37). In addition, the variant allele genotypes were associated with higher bladder cancer risk in ever smokers (OR=1.78; 95% CI=1.06-3.00), but not in never smokers (OR=1.19; 95% CI=0.65-2.20). These results suggest that the NQO1 genetic polymorphism modulates bladder cancer risk, especially in men and ever smokers.
烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）：醌氧化还原酶（NQO1）是一种解毒酶，在保护细胞免受化学诱导的氧化应激、细胞毒性、致突变性和致癌性方面发挥着关键作用。NQO1通过阻止活性氧的产生以及还原某些环境致癌物，如硝基芳香化合物、杂环胺和可能的香烟烟雾冷凝物，来保护细胞免受氧化损伤。外显子6中的一个C→T单核苷酸多态性被证明会降低NQO1酶的活性，这可能会削弱NQO1提供的保护作用。因此，我们推测具有NQO1变异等位基因基因型的人患膀胱癌的风险更高。在一项正在进行的病例对照研究中，通过聚合酶链反应-限制性片段长度多态性成功鉴定了265例膀胱癌患者和261例年龄、性别和种族相匹配的对照者的NQO1基因型。对照者中变异NQO1等位基因的频率为18%，病例组为21%。在白种人中，NQO1的变异等位基因基因型与患膀胱癌的较高风险相关（优势比（OR）=1.51；95%置信区间（CI）=1.01 - 2.25）。对白种人的进一步分析显示，男性患膀胱癌的风险升高（OR=1.75；95% CI=1.08 - 2.85），而女性则未升高（OR=1.16；95% CI=0.57 - 2.37）。此外，变异等位基因基因型与曾经吸烟者患膀胱癌的较高风险相关（OR=1.78；95% CI=1.06 - 3.00），但与从不吸烟者无关（OR=1.19；95% CI=0.65 - 2.20）。这些结果表明，NQO1基因多态性调节膀胱癌风险，尤其是在男性和曾经吸烟者中。
