Molecular Epidemiology of Head and Neck Cancer
This chapter focuses on the molecular epidemiological studies on the roles of carcinogen metabolism and DNA repair in susceptibility to squamous cell carcinoma of the head and neck (SCCHN). The major risk factors for oropharyngeal cancers, also known as head and neck cancers, are tobacco and alcohol use. Only a fraction of individuals exposed to tobacco smoke and alcohol develop SCCHN, suggesting that there are differences in individual susceptibility to carcinogenesis and the impact of gene-environment interactions. Tobacco carcinogens undergo a series of metabolic activation and detoxification steps that determine the internal dose of exposure and ultimately impact the level of DNA damage incurred. Studies have shown that polymorphisms of genes controlling drug metabolisms and DNA repair may contribute to a variation of tobacco-induced carcinogenesis in the general population. Some genetic variants in cell-cycle genes may also be relevant in genetic susceptibility to SCCHN. There is large interindividual variation in cellular responses in the metabolism and detoxification of toxicants and in DNA repair. Interindividual effects in cellular responses could be due to genetically determined differences in enzyme expression, kinetics, or stability. Induction of enzymes from previous exposures or comorbidity may also contribute to cancer risk, and induction has a genetic component. © 2003 Elsevier Inc. All rights reserved.