Choi Ji-Yeob, Lee Kyoung-Mu, Cho Soo-Hun, Kim Soo-Woong, Choi Han-Yong, Lee Sang-Yoon, Im Hyoung-June, Yoon Ki Jung, Choi Hwang, Choi Inmi, Hirvonen Ari, Hayes Richard B, Kang Daehee
Department of Preventive Medicine, Seoul National University College of Medicine, Korea.
Pharmacogenetics. 2003 Jun;13(6):349-55. doi: 10.1097/00008571-200306000-00006.
Cytochrome P450 2E1 (CYP2E1) and NAD(P)H:quinone oxidoreductase (NQO1) catalyze the activation of some environmental procarcinogens present in tobacco smoke (i.e. nitrosoamines and heterocyclic amines). We conducted a hospital based case-control study to evaluate the potential association between genetic polymorphisms of CYP2E1 (C1019T in the 5' flanking region) and NQO1 (C609T in exon 6) and bladder cancer risk in Asian population.
The study population was comprised of 218 histologically confirmed prevalent bladder cancer cases and 199 controls without cancer or systemic illness. PCR-restriction fragment length polymorphism based methods were used for the genotyping analyses and unconditional logistic regression model for the statistical evaluations.
The risk of bladder cancer increased with the amount of smoking (P for trend < 0.01). The frequency of CYP2E1 c1/c1 genotype was significantly higher in bladder cancer patients (57.9%) than in the controls (47.9%) (OR = 1.8, 95% CI = 1.1-2.9). Similarly, the NQO1 C/C genotypes were significantly more prevalent in the patients (45.8%) than in the controls (37.6%) (OR = 1.6, 95% CI = 1.0-2.7). The risk for bladder cancer increased with the number of the putative risk genotypes (P for trend = 0.03); the most remarkable risk was observed for heavy smokers with both CYP2E1 c1/c1 and NQO1 C/C genotypes (OR = 13.8, 95% CI = 3.9-48.6) when compared to non/light smokers with other genotypes.
Our findings suggest that CYP2E1 and NQO1 genotypes may play an important role in development of smoking related bladder cancer among Korean men.
细胞色素P450 2E1（CYP2E1）和NAD（P）H：醌氧化还原酶（NQO1）催化烟草烟雾中某些环境致癌物（即亚硝胺和杂环胺）的活化。我们进行了一项基于医院的病例对照研究，以评估CYP2E1（5'侧翼区域的C1019T）和NQO1（外显子6中的C609T）基因多态性与亚洲人群膀胱癌风险之间的潜在关联。
研究人群包括218例经组织学确诊的现患膀胱癌病例和199例无癌症或全身性疾病的对照。基于聚合酶链反应-限制性片段长度多态性的方法用于基因分型分析，无条件逻辑回归模型用于统计评估。
膀胱癌风险随吸烟量增加而升高（趋势P<0.01）。膀胱癌患者中CYP2E1 c1/c1基因型频率（57.9%）显著高于对照组（47.9%）（比值比=1.8，95%可信区间=1.1-2.9）。同样，NQO1 C/C基因型在患者中（45.8%）比对照组（37.6%）更普遍（比值比=1.6，95%可信区间=1.0-2.7）。膀胱癌风险随假定风险基因型数量增加而升高（趋势P=0.03）；与其他基因型的非/轻度吸烟者相比，CYP2E1 c1/c1和NQO1 C/C基因型的重度吸烟者风险最高（比值比=13.8，95%可信区间=3.9-48.6）。
我们的研究结果表明，CYP2E1和NQO1基因型可能在韩国男性吸烟相关膀胱癌的发生中起重要作用。
