Risk of Head and Neck Cancer and the Alcohol Dehydrogenase 3 Genotype

Squamous cell carcinoma of the head and neck (SCCHN), including the oral cavity, pharynx and larynx, is an excellent tumor model to evaluate gene-environment interactions, including alcohol and alcohol-metabolizing enzymes such as alcohol dehydrogenase (ADH). We conducted a hospital-based case-control study including 182 cases with newly diagnosed SCCHN and 202 controls with non-neoplastic conditions of the head and neck that required surgery. The joint effects of lifetime alcohol use and the presence of the ADH3 'rapid' allele (ADH3(*)1) was evaluated in relation to the risk of SCCHN. Logistic regression was used to estimate the interaction between alcohol use and ADH3 genotype with adjustment for tobacco use, age, sex and race. The interaction was evaluated on both the multiplicative and additive scales. The risk of SCCHN was increased nearly 6-fold with consumption of 40 or more alcoholic beverages per week [odds ratio (OR) = 5.9; 95% confidence interval (CI) = 2.0-17.7; adjusted for age, sex, race and years of tobacco use]. We did not find any increase in risk for ADH3*1 homozygotes (OR = 0.9; CI = 0.4-1.9) or heterozygotes (OR = 0.8; CI = 0.4-1.7) relative to ADH3(*)2 homozygotes. There was no suggestion of an interaction between any alcohol use variable and the ADH3(*)1 genotype. For example, the interaction term, including the continuous variable average number of drinks per week and the ADH3 genotypes, was non-significant (P = 0.22). The study does not indicate an important role for the ADH3 (*)1 polymorphism in SCCHN, but larger numbers are needed to more precisely estimate the interaction, if any, with ADH3.