[Susceptibility to bronchial cancer: an example of genetic-environmental interaction]

Tobacco is responsible for 80 to 90% lung cancer cases in industrialized countries. However, genetic factors are likely to be involved in lung cancer susceptibility. Some degree of familial aggregation of lung cancer is evidenced in most family studies. On the other hand, many tobacco carcinogens are metabolised by enzymes of the P450 cytochrome family. Two enzymes of cytochrome P450, CYP1A1 and CYP1A2, are inducible by tobacco carcinogens, and animal studies evidenced a genetic polymorphism of CYP1A1 associated with tumour occurrence after administration of a polycyclic aromatic hydrocarbon. In humans, an association between lung cancer and some P450 polymorphisms (CYP1A1, CYP2D6, CYP2E1) was suggested but the results of epidemiologic studies are discordant and difficult to interpret. In addition, there is a polymorphism of glutathione S-transferase isoenzyme (GSTM1) involved in carcinogen elimination; an association between this polymorphism and lung cancer has also been reported. Further studies on combined effects of these polymorphisms should allow an identification of sub-groups of individuals at high risk of lung cancer.