Carcinogenesis, Vol. 23, No. 11, 1851-1859,
November 2002
© 2002 Oxford University Press
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Genetic polymorphisms of alcohol and aldehyde dehydrogenases and glutathione S-transferase M1 and drinking, smoking, and diet in Japanese men with esophageal squamous cell carcinoma
1 National Institute on Alcoholism, Kurihama National Hospital, Yokosuka, Kanagawa 239-0841,
2 Surgery Division, National Cancer Center Hospital and
11 Cancer Information and Epidemiology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045,
3 Department of Technology Assessment and Biostatistics, National Institute of Public Health, Wako, Saitama 351-0104,
4 Department of Surgery, National Osaka Hospital, Osaka, Osaka 540-0006,
5 Internal Medicine Division, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577,
6 Department of Surgery, Kawasaki Municipal Hospital, Kawasaki, Kanagawa 210-0013,
7 Kamio Memorial Hospital, Chiyoda-ku, Tokyo 101-0063,
8 Kumagai Satellite Clinic, Shinjuku-ku, Tokyo 169-0074,
9 Mitsukoshi Health and Welfare Foundation, Shinjuku-ku, Tokyo 160-0023,
10 Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan
The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-2 (ADH2), ADH3, and glutathione S-transferase M1 (GSTM1) influence the metabolism of alcohol and other carcinogens. The ALDH2*1/2*2 genotype, which encodes inactive ALDH2, and ADH2*1/2*1, which encodes the low-activity form of ADH2, enhance the risk for esophageal cancer in East Asian alcoholics. This case–control study of whether the enzyme-related vulnerability for esophageal cancer can be extended to a general population involved 234 Japanese men with esophageal squamous cell carcinoma and 634 cancer-free Japanese men who received annual health checkups. The GSTM1 genotype was not associated with the risk for this cancer. Light drinkers (1–8.9 units/week) with ALDH2*1/2*2 had an esophageal cancer risk 5.82 times that of light drinkers with ALDH2*1/2*1 (reference category), and their risk was similar to that of moderate drinkers (9–17.9 units/week) with ALDH2*1/2*1 (odds ratio = 5.58). The risk for moderate drinkers with ALDH2*1/2*2 (OR = 55.84) exceeded that for heavy drinkers (18+ units/week) with ALDH2*1/2*1 (OR = 10.38). Similar increased risks were observed for those with ADH2*1/2*1. A multiple logistic model including ALDH2, ADH2, and ADH3 genotypes showed that the ADH3 genotype does not significantly affect the risk for esophageal cancer. For individuals with both ALDH2*1/2*2 and ADH2*1/2*1, the risk of esophageal cancer was enhanced in a multiplicative fashion (OR = 30.12), whereas for those with either ALDH2*1/2*2 or ADH2*1/2*1 alone the ORs were 7.36 and 4.11. In comparison with the estimated population-attributable risks for preference for strong alcoholic beverages (30.7%), smoking (53.6%) and for lower intake of green and yellow vegetables (25.7%) and fruit (37.6%), an extraordinarily high proportion of the excessive risk for esophageal cancer in the Japanese males can be attributed to drinking (90.9%), particularly drinking by persons with inactive heterozygous ALDH2 (68.5%). Education regarding these risky conditions in connection with ALDH2 and ADH2 is vitally important in a new strategic approach aimed at preventing esophageal cancer in East Asians.
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