Gene-environment interaction in tobacco-related cancers.

This review summarizes the carcinogenic effects of tobacco smoke and the basis for interaction between tobacco smoke and genetic factors. Examples of published papers on gene-tobacco interaction and cancer risk are presented. The assessment of gene-environment interaction in tobacco-related cancers has been more complex than originally expected for several reasons, including the multiplicity of genes involved in tobacco metabolism, the numerous substrates metabolized by the relevant genes and the interaction of smoking with other metabolic pathways. Future studies on gene-environment interaction and cancer risk should include biomarkers of smoking dose, along with markers of quantitative historical exposure to tobacco. Epigenetic studies should be added to classic genetic analyses, in order to better understand gene-environmental interaction and individual susceptibility. Other metabolic pathways in competition with tobacco genetic metabolism/repair should be incorporated in epidemiological studies to generate a more complete picture of individual cancer risk associated with environmental exposure to carcinogens.