Cigarette smoking is incontrovertibly the major risk factor for lung cancer.
However most environmental carcinogens, including those in tobacco smoke, require metabolic activation by cytochrome P450 enzymes in order to exert their deleterious effects. Conversely, endogenous detoxication enzymes, such as glutathione S-transerases, can react with these activated intermediates. Polymorphisms exist in the genes responsible for both activation and inactivation and may contribute to interindividual differences in susceptibility to lung carcinogens. The possible association between biologically relevant polymorphisms of carcinogens metabolism enzymes and lung cancer risk is being studied in two different study populations. The second population is a cohort study of 18,000 men in Shanghai.