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Alcohol dehydrogenase 3 genotype and risk of oral cavity and pharyngeal cancers
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1997
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Alcohol consumption is a major risk factor for oral cavity and pharyngeal cancers, and ADH3 converts ethanol to the carcinogenic acetaldehyde. The study examined whether individuals homozygous for the fast‑metabolizing ADH3(1‑1) allele have a higher risk of oral cancer when consuming alcohol compared to carriers of the slow‑metabolizing ADH3(2) allele. In a Puerto Rican population‑based case‑control study, ADH3 genotypes of 137 oral cancer patients and 146 controls were determined, and multiple logistic regression was used to estimate risks. Drinkers with the ADH3(1‑1) genotype had markedly higher oral cancer risk—40.1‑fold versus 7.0‑fold for ADH3(1‑2) and 4.4‑fold for ADH3(2‑2)—and each additional alcoholic drink increased risk by 3.6% for ADH3(1‑1) carriers and 2.0% for ADH3(1‑2)/ADH3(2‑2) carriers.
The consumption of alcoholic beverages is a strong risk factor for cancers of the oral cavity and pharynx (oral cancers). Alcohol dehydrogenase type 3 (ADH3) metabolizes ethanol to acetaldehyde, a carcinogen. We evaluated whether individuals homozygous for the fast-metabolizing ADH3(1) allele (ADH3[1-1]) have a greater risk of developing oral cancer in the presence of alcoholic beverage consumption than those with the slow-metabolizing ADH3(2) allele (ADH3[1-2] and ADH3[2-2]).As part of a population-based study of oral cancer conducted in Puerto Rico, the ADH3 genotypes of 137 patients with histologically confirmed oral cancer and of 146 control subjects (i.e., individuals with no history of oral cancer) were determined by molecular genetic analysis of oral epithelial cell samples. Risks were estimated by use of multiple logistic regression analyses.Compared with nondrinkers with the ADH3(1-1) genotype, consumers of at least 57 alcoholic drinks per week with the ADH3(1-1), ADH3(1-2), and ADH3(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 associated with the ADH3(1-1) genotype, compared with the ADH3(1-2) and ADH3(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 oral cancer per additional alcoholic drink per week increased 3.6% (95% CI = 1.9%-5.4%) for subjects with the ADH3(1-1) genotype and 2.0% (95% CI = 0.9%-3.0%) for subjects with the ADH3(1-2) or ADH3(2-2) genotype (two-sided P = .04).The ADH3(1-1) genotype appears to substantially increase the risk of ethanol-related oral cancer, thus providing further evidence for the carcinogenicity of acetaldehyde.