title: Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking, smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma.
abstract: The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-1B (ADH1B, previously called ADH2), and ADH1C (previously called ADH3) affect the metabolism of alcohol. The inactive ALDH2 encoded by ALDH2*1/*2 and the less-active ADH1B encoded by ADH1B*1/*1 increase 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, by ALDH2*1/*2 among 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 the ALDH2 genotype. The results obtained with a simple alcohol flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping. Among moderate-to-heavy drinkers, men with the less-active ADH1B*1/*1 had 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 between ADH1B and ADH1C, the ADH1C genotype does not significantly affect cancer risk. The significant independent risk factors for oral and pharyngeal cancer overall among moderate-to-heavy drinkers were inactive ALDH2*1/*2, less-active ADH1B*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.
authors.affiliation: Department of Otorlaryngology, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan. tasakage-tky@umin.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Asakage
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Tatsumasa
authors.initials: T
authors.lastname: Haneda
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Manabu
authors.initials: M
authors.lastname: Muto
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hoichi
authors.initials: H
authors.lastname: Kato
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Igaki
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Tsujinaka
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Masako
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Tai
authors.initials: T
authors.lastname: Omori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D004032:Diet; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D010610:Pharyngeal Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking; D011795:Surveys and Questionnaires
chemical_list: C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial