ALCOHOL-DEHYDROGENASE-3 GENOTYPE AND RISK OF ORAL CAVITY AND PHARYNGEAL CANCERS

Background: The consumption of alcoholic beverages is a strong risk fa ctor for cancers of the oral cavity and pharynx (oral cancers). Alcoho l dehydrogenase type 3 (ADH(3)) metabolizes ethanol to acetaldehyde, a carcinogen. We evaluated whether individuals homozygous for the fast- metabolizing ADH(3)(1) allele (ADH(3)(1-1)) have a greater risk of dev eloping oral cancer in the presence of alcoholic beverage consumption than those with the slow-metabolizing ADH(3)(2) allele (ADH(3)(1-2) an d ADH(3)(2-2)). Methods: As part of a population-based study of oral c ancer conducted in Puerto Rico, the ADH(3) genotypes of 137 patients w ith histologically confirmed oral cancer and of 146 control subjects ( i.e., individuals with no history of oral cancer) were determined by m olecular genetic analysis of oral epithelial cell samples. Risks were estimated by use of multiple logistic regression analyses. Results: Co mpared with nondrinkers with the ADH(3)(1-1) genotype, consumers of at least 57 alcoholic drinks per week with the ADH(3)(1-1), ADH(3)(1-2), and ADH(3)(2-2) genotypes had 40.1-fold (95% confidence interval [CI] = 5.4-296.0), 7.0-fold (95% CI = 1.4-35.0), and 4.4-fold (95% CI = 0. 6-33.0) increased risks of oral cancer, respectively; the risk associa ted with the ADH(3)(1-1) genotype, compared with the ADH(3)(1-2) and A DH(3)(2-2) genotypes combined, was 5.3 (95% CI = 1.0-28.8) among such drinkers. Considering all levels of alcohol consumption. the risk of o ral cancer per additional alcoholic drink per week increased 3.6% (95% CI = 1.9%-5.4%) for subjects with the ADH(3)(1-1) genotype and 2.0% ( 95% CI = 0.9%-3.0%) for subjects with the ADH(3)(1-2) or ADH(3)(2-2) g enotype (two-sided P = .04). Conclusions: The ADH(3)(1-1) genotype app ears to substantially increase the risk of ethanol-related oral cancer , thus providing further evidence for the carcinogenicity of acetaldeh yde.