Metabolic polymorphisms as susceptibility markers for lung and oral cavity cancer.

Lung and oral cavity cancers are causally associated with tobacco use. Alcohol is an independent risk factor for oral cavity cancer. Major classes of carcinogens present in tobacco and tobacco smoke are converted into DNA-reactive metabolites by cytochrome P450 (CYP)-related enzymes, several of which display genetic polymorphism. Individual susceptibility to cancer is likely to be modified by the genotype for enzymes involved in the activation or detoxification of carcinogens in tobacco and repair of DNA damage. Molecular epidemiological studies to assess the risk associated with metabolic polymorphisms for cancers of the lung and head and neck have shown that the overall effect of common polymorphisms is moderate in terms of penetrance and relative risk. However, some gene combinations like mutated CYP1A1/GSTM1-null genotype seem to predispose the lung and oral cavity of smokers to an even higher risk for cancer or DNA damage, although these results require confirmation in larger well defined studies that take into account the existence of ethnic variations even within the commonly defined groups. Retinoids, isothiocyanates and tea polyphenols have been identified as possible chemopreventive agents for cancers of the lung and oral cavity. While a number of trials have been conducted with retinoids or beta-carotene, the results were ambiguous and the causes are still being debated. The possible interaction of chemopreventive agents with metabolic polymorphisms as biomarkers in chemoprevention trials is discussed.