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The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-1B (ADH1B, previously calledADH2), andADH1C(previously calledADH3) affect the metabolism of alcohol. The inactiveALDH2encoded byALDH2*1/*2and the less-activeADH1Bencoded byADH1B*1/*1increase the risk of esophageal squamous cell carcinoma in East Asian drinkers. This case–control study involved 96 Japanese men with oral and pharyngeal squamous cell carcinoma (hypopharyngeal cancer in 43 patients and oral/oropharyngeal cancer in 53) and 642 cancer-free Japanese men. The risk of the cancers overall and of hypopharyngeal cancer was increased 3.61- and 10.08-fold, respectively, byALDH2*1/*2among moderate-to-heavy drinkers (9+ units/week; one unit = 22 g of ethanol), but the risk of oral/oropharyngeal cancer was not significantly affected by theALDH2genotype. The results obtained with a simple alcohol flushing questionnaire were essentially comparable with those obtained byALDH2genotyping. Among moderate-to-heavy drinkers, men with the less-activeADH1B*1/*1had a significantly higher risk of the cancers overall, of hypopharyngeal cancer, and of oral/oropharyngeal cancer (OR = 5.56, 7.21 and 4.24, respectively). In view of the linkage disequilibrium betweenADH1BandADH1C, theADH1Cgenotype does not significantly affect cancer risk. The significant independent risk factors for oral and pharyngeal cancer overall among moderate-to-heavy drinkers were inactiveALDH2*1/*2, less-activeADH1B*1/*1, frequent drinking of strong alcohol beverages straight, smoking, and lower intake of green–yellow vegetables. Educating these risks for cancer of the upper aerodigestive tract could be a useful new strategic approach to the prevention of these cancers in Japanese.

carcinogenesis

Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking, smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma