Carcinogenesis Advance Access originally published online on October 27, 2006
Carcinogenesis 2007 28(4):865-874; doi:10.1093/carcin/bgl206
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Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking, smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma
Department of Otorlaryngology, University of Tokyo Bunkyo-ku, Tokyo 113-8655, Japan
1 National Hospital Organization Kurihama Alcoholism Center Yokosuka, Kanagawa 239-0841, Japan
2 Kamio Memorial Hospital Chiyoda-ku, Tokyo 104-0045, Japan
3 Division of Head and Neck Surgery, National Cancer Center Hospital East Kashiwa, Chiba 277-8577, Japan
4 Division of Digestive Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East Kashiwa, Chiba 277-8577, Japan
5 Department of Technology Assessment and Biostatistics, National Institute of Public Health Wako, Saitama 351-0104, Japan
6 Surgery Division, National Cancer Center Hospital Chuo-ku, Tokyo 104-0045
7 Department of Surgery, Osaka National Hospital Osaka, Osaka 540-0006, Japan
8 Kumagai Satellite Clinic, Shinjuku-ku Tokyo 169-0074, Japan
9 Mitsukoshi Health and Welfare Foundation, Shinjuku-ku Tokyo 160-0023, Japan
10 Departments of Surgery and Gastroenterology, Kawasaki Municipal Hospital Kawasaki, Kanagawa 210-0013, Japan
11 Department of Surgery, School of Medicine, Keio University Shinjuku-ku, Tokyo 160-8582, Japan
*To whom correspondence should be addressed. Email: tasakage-tky{at}umin.ac.jp
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.
Abbreviations: ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase
Received July 18, 2006; revised October 3, 2006; accepted October 18, 2006.