Benhamou S, Reinikainen M, Bouchardy C, Dayer P, Hirvonen A
Unit of Cancer Epidemiology (INSERM U351), Institut Gustave-Roussy, Villejuif, France.
Cancer Res. 1998 Dec 1;58(23):5291-3.
Microsomal epoxide hydrolase (mEH) is involved in the metabolism of tobacco-derived carcinogens. Polymorphisms in exons 3 and 4 of the EPHX gene have been reported to be associated with variations in mEH activity. We examined whether the predicted mEH activity modified the lung cancer risk among 150 cases and 172 controls, all French Caucasian smokers. A significant association was found between predicted mEH activity and lung cancer (P < 0.02), with a dose-effect relationship (P < 0.005). The risks associated with intermediate and high activities, compared to low activity, were 1.65 (95% CI, 0.95-2.86) and 2.66 (95% CI, 1.33-5.33), respectively. The effect of mEH activity on lung cancer risk was not significantly modified by smoking exposure, CYP1A1 genotype, or GSTM1 genotype. mEH may thus be an important genetic determinant of smoking-induced lung cancer.
微粒体环氧化物水解酶（mEH）参与烟草衍生致癌物的代谢。据报道，EPHX基因外显子3和4中的多态性与mEH活性的变化有关。我们在150例肺癌病例和172例对照（均为法国白种人吸烟者）中研究了预测的mEH活性是否会改变肺癌风险。结果发现预测的mEH活性与肺癌之间存在显著关联（P < 0.02），且呈剂量效应关系（P < 0.005）。与低活性相比，中等活性和高活性相关的风险分别为1.65（95%可信区间，0.95 - 2.86）和2.66（95%可信区间，1.33 - 5.33）。吸烟暴露、CYP1A1基因型或GSTM1基因型并未显著改变mEH活性对肺癌风险的影响。因此，mEH可能是吸烟诱导肺癌的一个重要遗传决定因素。
