Cancer Epidemiology Biomarkers & Prevention, Vol 5, Issue 2 99-102, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Esophageal cancer and aldehyde dehydrogenase-2 genotypes in Japanese males

A Yokoyama, T Muramatsu, T Ohmori, S Higuchi, M Hayashida and H Ishii
National Institute on Alcoholism, Kurihama National Hospital, Kanagawa, Japan.

Although drinking alcohol is an established esophageal cancer risk factor, the mechanisms by which alcohol induces this high-mortality rate cancer are not clear. To help elucidate this problem and develop an implementable preventive strategy, this genetic epidemiological study focused on aldehyde dehydrogenase 2 (ALDH2), the key enzyme for elimination of acetaldehyde generated by alcohol consumption. This enzyme is polymorphic; its mutant allele, ALDH2*2, which leads to the enzyme inactivity, is prevalent in Orientals. This Japanese case-control study of ALDH2-related risk for esophageal squamous cell carcinoma included alcoholics (40 cases and 55 controls) and nonalcoholic drinkers (29 cases and 28 controls). The analysis of the results of genotyping these subjects showed that the increased risk for esophageal cancer in those with one ALDH2*2 allele was substantially higher in both alcoholics (odds ratio = 7.6; 95% confidence interval = 2.8-20.7) and nonalcoholic drinkers (odds ratio = 12.1; 95% confidence interval = 3.4-42.8). The results strongly suggest that because persons who have this mutant ALDH2*2 allele have a high concentration of blood acetaldehyde after drinking alcohol, acetaldehyde (a recognized animal carcinogen) plays a pivotal role in the pathogenesis of alcohol-related esophageal cancer in humans. These results suggest that to help lower their risk for esophageal cancer, persons with the ALDH2*2 allele should be encouraged to reduce their consumption of alcoholic beverages.

This article has been cited by other articles:

				M. Inoue, K. Wakai, C. Nagata, T. Mizoue, K. Tanaka, I. Tsuji, S. Tsugane, and for the Research Group for the Development and Eva Alcohol Drinking and Total Cancer Risk: An Evaluation Based on a Systematic Review of Epidemiologic Evidence among the Japanese Population Jpn. J. Clin. Oncol., September 1, 2007; 37(9): 692 - 700. [Abstract] [Full Text] [PDF]

				A. Yokoyama, T. Omori, T. Yokoyama, Y. Sato, T. Mizukami, S. Matsushita, S. Higuchi, K. Maruyama, H. Ishii, and T. Hibi Risk of Squamous Cell Carcinoma of the Upper Aerodigestive Tract in Cancer-Free Alcoholic Japanese Men: An Endoscopic Follow-up Study. Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2209 - 2215. [Abstract] [Full Text] [PDF]

				M. Hashibe, P. Boffetta, D. Zaridze, O. Shangina, N. Szeszenia-Dabrowska, D. Mates, V. Janout, E. Fabianova, V. Bencko, N. Moullan, et al. Evidence for an important role of alcohol- and aldehyde-metabolizing genes in cancers of the upper aerodigestive tract. Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 696 - 703. [Abstract] [Full Text] [PDF]

				M. Muto, M. Takahashi, A. Ohtsu, S. Ebihara, S. Yoshida, and H. Esumi Risk of multiple squamous cell carcinomas both in the esophagus and the head and neck region Carcinogenesis, May 1, 2005; 26(5): 1008 - 1012. [Abstract] [Full Text] [PDF]

				W.-c. You, J.-Y. Hong, L. Zhang, K.-f. Pan, D. Pee, J.-y. Li, J.-l. Ma, N. Rothman, N. Caporaso, J. F. Fraumeni Jr., et al. Genetic Polymorphisms of CYP2E1, GSTT1, GSTP1, GSTM1, ALDH2, and ODC and the Risk of Advanced Precancerous Gastric Lesions in a Chinese Population Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 451 - 458. [Abstract] [Full Text] [PDF]

				T. Yokoyama, A. Yokoyama, H. Kato, T. Tsujinaka, M. Muto, T. Omori, T. Haneda, Y. Kumagai, H. Igaki, M. Yokoyama, et al. Alcohol Flushing, Alcohol and Aldehyde Dehydrogenase Genotypes, and Risk for Esophageal Squamous Cell Carcinoma in Japanese Men Cancer Epidemiol. Biomarkers Prev., November 1, 2003; 12(11): 1227 - 1233. [Abstract] [Full Text]

				L. M. Morimoto, E. White, and P. A. Newcomb Selection Bias in the Assessment of Gene-Environment Interaction in Case-Control Studies Am. J. Epidemiol., August 1, 2003; 158(3): 259 - 263. [Abstract] [Full Text] [PDF]

				A. Yokoyama and T. Omori Genetic Polymorphisms of Alcohol and Aldehyde Dehydrogenases and Risk for Esophageal and Head and Neck Cancers Jpn. J. Clin. Oncol., March 1, 2003; 33(3): 111 - 121. [Abstract] [Full Text] [PDF]

				A. Yokoyama, H. Kato, T. Yokoyama, T. Tsujinaka, M. Muto, T. Omori, T. Haneda, Y. Kumagai, H. Igaki, M. Yokoyama, et al. 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 Carcinogenesis, November 1, 2002; 23(11): 1851 - 1859. [Abstract] [Full Text] [PDF]

				A. Yokoyama, H. Watanabe, H. Fukuda, T. Haneda, H. Kato, T. Yokoyama, T. Muramatsu, H. Igaki, and Y. Tachimori Multiple Cancers Associated with Esophageal and Oropharyngolaryngeal Squamous Cell Carcinoma and the Aldehyde Dehydrogenase-2 Genotype in Male Japanese Drinkers Cancer Epidemiol. Biomarkers Prev., September 1, 2002; 11(9): 895 - 900. [Abstract] [Full Text] [PDF]

				K. Matsuo, N. Hamajima, M. Shinoda, S. Hatooka, M. Inoue, T. Takezaki, and K. Tajima Gene-environment interaction between an aldehyde dehydrogenase-2 (ALDH2) polymorphism and alcohol consumption for the risk of esophageal cancer Carcinogenesis, June 1, 2001; 22(6): 913 - 916. [Abstract] [Full Text] [PDF]

				A. Yokoyama, T. Muramatsu, T. Omori, T. Yokoyama, S. Matsushita, S. Higuchi, K. Maruyama, and H. Ishii Alcohol and aldehyde dehydrogenase gene polymorphisms and oropharyngolaryngeal, esophageal and stomach cancers in Japanese alcoholics Carcinogenesis, March 1, 2001; 22(3): 433 - 439. [Abstract] [Full Text] [PDF]

				N. Homann, J. Tillonen, J. H. Meurman, H. Rintamaki, C. Lindqvist, M. Rautio, H. Jousimies-Somer, and M. Salaspuro Increased salivary acetaldehyde levels in heavy drinkers and smokers: a microbiological approach to oral cavity cancer Carcinogenesis, April 1, 2000; 21(4): 663 - 668. [Abstract] [Full Text] [PDF]