Association between lung cancer and microsomal epoxide hydrolase genotypes

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 associ ation was found between predicted mEH activity and Lung cancer (P < 0.02), with a dose-effect relationship (P < 0.005). The risks associated with inte rmediate 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 ac tivity on lung cancer risk was not significantly modified by smoking exposu re, CYP1A1 genotype, or GSTM1 genotype, mEH may thus be an important geneti c determinant of smoking-induced lung cancer.