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Distribution and gene--environment interaction of EPHX1 polymorphism was evaluated in 175 lung cancer patients and 322 controls from north India. Two novel non-synonymous, Lys117Arg and Leu263Phe, and twelve single nucleotide polymorphisms were identified in the present study. Binary logistic regression analysis showed association of polymorphism Tyr113His with increased risk of lung cancer (OR == 2.2, 95%% CI == 1.2--4.0, p < .05). Gene--environment interaction revealed that patients with His113His and smoking habit had significantly greater risk of lung cancer (OR == 4.52, 95%% CI == 0.93--43.05, p < .05). Present study provided evidence that EPHX1 polymorphism is associated with lung cancer susceptibility in Indian population. [ABSTRACT FROM AUTHOR]