Polymorphisms in the Human Cytochrome P450 and ArylamineN-Acetyltransferase: Susceptibility to Head and Neck Cancers

The occurrence of head and neck cancer (HNC) is associated with smoking and alcohol drinking. Tobacco smoking exposes smokers to a series of carcinogenic chemicals. Cytochrome P450 enzymes (CYP450s), such asCYP1A1,CYP1B1, andCYP2D6, usually metabolize carcinogens to their inactive derivatives, but they occasionally convert the chemicals to more potent carcinogens. In addition, viaCYP450(CYP2E1) oxidase, alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Furthermore, twoN-acetyltransferase isozymes (NATs),NAT1andNAT2, are polymorphic and catalyze bothN-acetylation andO-acetylation of aromatic and heterocyclic amine carcinogens. Genetic polymorphisms are associated with a number of enzymes involved in the metabolism of carcinogens important in the induction of HNC. It has been suggested that such polymorphisms may be linked to cancer susceptibility. In this paper, we select four cytochromeP450enzymes (CYP1A1,CYP1BA1,CYP2D6, andCYP2E1), and twoN-acetyltransferase isozymes (NAT1andNAT2) in order to summarize and analyze findings from the literature related to HNC risk by focusing on (i) the interaction between these genes and the environment, (ii) the impact of genetic defect on protein activity and/or expression, and (iii) the eventual involvement of race in such associations.