Risk factors and genetic susceptibility.

Upper aerodigestive tract (oral cavity, pharyngeal, and laryngeal) cancers are sentinel diseases of exposure to tobacco and alcohol, and thus can be considered the paradigm of environmentally induced disease. The fact that only a fraction of exposed individuals develop these cancers suggests interindividual differences in susceptibility to these environmental insults. In fact, heritable differences in susceptibility may be identified at almost every phase of carcinogenesis, for example, in the ability to metabolize carcinogens, DNA repair capability, genomic instability, and altered protooncogene and tumor suppressor gene expression [1]. This chapter will review briefly the environmental contribution to the incidence of upper aerodigestive tract cancers and will explore some of the host factors that modify genetic damage from these and other carcinogenic exposures.