Alcohol and aldehyde dehydrogenase gene polymorphisms influence susceptibility to esophageal cancer in Japanese alcoholics

Akira Yokoyama, Taro Muramatsu, Tai Omori, Sachio Matsushita, Haruko Yoshimizu, Susumu Higuchi, Tetsuji Yokoyama, Katsuya Maruyama, Hiromasa Ishii

Research output: Contribution to journalArticle

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Abstract

Background: Studies have consistently demonstrated that inactive aldehyde dehydrogenase-2 (ALDH2), encoded by ALDH2*1/2*2, is closely associated with alcohol-related carcinogenesis. Recently, the contributions of alcohol dehydrogenase-2 (ADH2) polymorphism to alcoholism, esophageal cancer, and the flushing response have also been described. Methods: To determine the effects of ALDH2 and ADH2 genotypes in genetically based cancer susceptibility, lymphocyte DNA samples from 668 Japanese alcoholic men more than 40 years of age (91 with and 577 without esophageal cancer) were genotyped and the results were expressed as odds ratios (ORs). This study also tested 82 of the alcoholics with esophageal cancer to determine whether cancer susceptibility is associated with patients' responses to simple questions about current or former flushing after drinking a glass of beer. Results: The frequencies of ADH2*1/2*1 and ALDH2*1/2*2 were significantly higher in alcoholics with, than in those without, esophageal cancer (0.473 vs. 0.289 and 0.560 vs. 0.099, respectively). After adjustment for drinking and smoking, the analysis showed significantly increased cancer risk for alcoholics with either ADH2*1/2*1 (OR = 2.03) or ALDH2*1/2*2 (OR = 12.76). For those having ADH2*1/2*1 combined with ALDH2*1/2*2, the esophageal cancer risk was enhanced in a multiplicative fashion (OR = 27.66). Responses to flushing questions showed that only 47.8% of the ALDH2*1/2*2 hetcrozygotes with ADH2*1/2*1, compared with 92.3% of those with ALDH2*l/2*2 and the ADH2*2 allele, reported current or former flushing. Genotyping showed that for alcoholics who reported ever flushing, the questionnaire was 71.4% correct in identifying ALDH2*1/2*2 and 87.9% correct in identifying ALDH2*1/2*1. Conclusion: Japanese alcoholics can be divided into cancer susceptibility groups on the basis of their combined ADH2 and ALDH2 genotypes. The flushing questionnaire can predict high risk ALDH2*1/2*2 fairly accurately in persons with ADH2*2 allele, but a reliable screening procedure for the highest risk gene combination (ADH2*1/2*1 and ALDH2*1/2*2) will require further investigation.

Original languageEnglish
Pages (from-to)1705-1710
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume23
Issue number11
Publication statusPublished - 1999 Nov

Fingerprint

Aldehyde Dehydrogenase
Alcohol Dehydrogenase
Alcoholics
Esophageal Neoplasms
Polymorphism
Genes
Odds Ratio
Drinking
Neoplasms
Alleles
Genotype
aldehyde dehydrogenase 1
Beer
Lymphocytes
Alcoholism
Glass
Carcinogenesis
Smoking
Screening
Alcohols

Keywords

  • Alcohol Dehydrogenase
  • Alcoholism
  • Aldehyde Dehydrogenase
  • Esophageal Cancer
  • Flushing Response

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Alcohol and aldehyde dehydrogenase gene polymorphisms influence susceptibility to esophageal cancer in Japanese alcoholics. / Yokoyama, Akira; Muramatsu, Taro; Omori, Tai; Matsushita, Sachio; Yoshimizu, Haruko; Higuchi, Susumu; Yokoyama, Tetsuji; Maruyama, Katsuya; Ishii, Hiromasa.

In: Alcoholism: Clinical and Experimental Research, Vol. 23, No. 11, 11.1999, p. 1705-1710.

Research output: Contribution to journalArticle

Yokoyama, A, Muramatsu, T, Omori, T, Matsushita, S, Yoshimizu, H, Higuchi, S, Yokoyama, T, Maruyama, K & Ishii, H 1999, 'Alcohol and aldehyde dehydrogenase gene polymorphisms influence susceptibility to esophageal cancer in Japanese alcoholics', Alcoholism: Clinical and Experimental Research, vol. 23, no. 11, pp. 1705-1710.
Yokoyama, Akira ; Muramatsu, Taro ; Omori, Tai ; Matsushita, Sachio ; Yoshimizu, Haruko ; Higuchi, Susumu ; Yokoyama, Tetsuji ; Maruyama, Katsuya ; Ishii, Hiromasa. / Alcohol and aldehyde dehydrogenase gene polymorphisms influence susceptibility to esophageal cancer in Japanese alcoholics. In: Alcoholism: Clinical and Experimental Research. 1999 ; Vol. 23, No. 11. pp. 1705-1710.
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abstract = "Background: Studies have consistently demonstrated that inactive aldehyde dehydrogenase-2 (ALDH2), encoded by ALDH2*1/2*2, is closely associated with alcohol-related carcinogenesis. Recently, the contributions of alcohol dehydrogenase-2 (ADH2) polymorphism to alcoholism, esophageal cancer, and the flushing response have also been described. Methods: To determine the effects of ALDH2 and ADH2 genotypes in genetically based cancer susceptibility, lymphocyte DNA samples from 668 Japanese alcoholic men more than 40 years of age (91 with and 577 without esophageal cancer) were genotyped and the results were expressed as odds ratios (ORs). This study also tested 82 of the alcoholics with esophageal cancer to determine whether cancer susceptibility is associated with patients' responses to simple questions about current or former flushing after drinking a glass of beer. Results: The frequencies of ADH2*1/2*1 and ALDH2*1/2*2 were significantly higher in alcoholics with, than in those without, esophageal cancer (0.473 vs. 0.289 and 0.560 vs. 0.099, respectively). After adjustment for drinking and smoking, the analysis showed significantly increased cancer risk for alcoholics with either ADH2*1/2*1 (OR = 2.03) or ALDH2*1/2*2 (OR = 12.76). For those having ADH2*1/2*1 combined with ALDH2*1/2*2, the esophageal cancer risk was enhanced in a multiplicative fashion (OR = 27.66). Responses to flushing questions showed that only 47.8{\%} of the ALDH2*1/2*2 hetcrozygotes with ADH2*1/2*1, compared with 92.3{\%} of those with ALDH2*l/2*2 and the ADH2*2 allele, reported current or former flushing. Genotyping showed that for alcoholics who reported ever flushing, the questionnaire was 71.4{\%} correct in identifying ALDH2*1/2*2 and 87.9{\%} correct in identifying ALDH2*1/2*1. Conclusion: Japanese alcoholics can be divided into cancer susceptibility groups on the basis of their combined ADH2 and ALDH2 genotypes. The flushing questionnaire can predict high risk ALDH2*1/2*2 fairly accurately in persons with ADH2*2 allele, but a reliable screening procedure for the highest risk gene combination (ADH2*1/2*1 and ALDH2*1/2*2) will require further investigation.",
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T1 - Alcohol and aldehyde dehydrogenase gene polymorphisms influence susceptibility to esophageal cancer in Japanese alcoholics

AU - Yokoyama, Akira

AU - Muramatsu, Taro

AU - Omori, Tai

AU - Matsushita, Sachio

AU - Yoshimizu, Haruko

AU - Higuchi, Susumu

AU - Yokoyama, Tetsuji

AU - Maruyama, Katsuya

AU - Ishii, Hiromasa

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N2 - Background: Studies have consistently demonstrated that inactive aldehyde dehydrogenase-2 (ALDH2), encoded by ALDH2*1/2*2, is closely associated with alcohol-related carcinogenesis. Recently, the contributions of alcohol dehydrogenase-2 (ADH2) polymorphism to alcoholism, esophageal cancer, and the flushing response have also been described. Methods: To determine the effects of ALDH2 and ADH2 genotypes in genetically based cancer susceptibility, lymphocyte DNA samples from 668 Japanese alcoholic men more than 40 years of age (91 with and 577 without esophageal cancer) were genotyped and the results were expressed as odds ratios (ORs). This study also tested 82 of the alcoholics with esophageal cancer to determine whether cancer susceptibility is associated with patients' responses to simple questions about current or former flushing after drinking a glass of beer. Results: The frequencies of ADH2*1/2*1 and ALDH2*1/2*2 were significantly higher in alcoholics with, than in those without, esophageal cancer (0.473 vs. 0.289 and 0.560 vs. 0.099, respectively). After adjustment for drinking and smoking, the analysis showed significantly increased cancer risk for alcoholics with either ADH2*1/2*1 (OR = 2.03) or ALDH2*1/2*2 (OR = 12.76). For those having ADH2*1/2*1 combined with ALDH2*1/2*2, the esophageal cancer risk was enhanced in a multiplicative fashion (OR = 27.66). Responses to flushing questions showed that only 47.8% of the ALDH2*1/2*2 hetcrozygotes with ADH2*1/2*1, compared with 92.3% of those with ALDH2*l/2*2 and the ADH2*2 allele, reported current or former flushing. Genotyping showed that for alcoholics who reported ever flushing, the questionnaire was 71.4% correct in identifying ALDH2*1/2*2 and 87.9% correct in identifying ALDH2*1/2*1. Conclusion: Japanese alcoholics can be divided into cancer susceptibility groups on the basis of their combined ADH2 and ALDH2 genotypes. The flushing questionnaire can predict high risk ALDH2*1/2*2 fairly accurately in persons with ADH2*2 allele, but a reliable screening procedure for the highest risk gene combination (ADH2*1/2*1 and ALDH2*1/2*2) will require further investigation.

AB - Background: Studies have consistently demonstrated that inactive aldehyde dehydrogenase-2 (ALDH2), encoded by ALDH2*1/2*2, is closely associated with alcohol-related carcinogenesis. Recently, the contributions of alcohol dehydrogenase-2 (ADH2) polymorphism to alcoholism, esophageal cancer, and the flushing response have also been described. Methods: To determine the effects of ALDH2 and ADH2 genotypes in genetically based cancer susceptibility, lymphocyte DNA samples from 668 Japanese alcoholic men more than 40 years of age (91 with and 577 without esophageal cancer) were genotyped and the results were expressed as odds ratios (ORs). This study also tested 82 of the alcoholics with esophageal cancer to determine whether cancer susceptibility is associated with patients' responses to simple questions about current or former flushing after drinking a glass of beer. Results: The frequencies of ADH2*1/2*1 and ALDH2*1/2*2 were significantly higher in alcoholics with, than in those without, esophageal cancer (0.473 vs. 0.289 and 0.560 vs. 0.099, respectively). After adjustment for drinking and smoking, the analysis showed significantly increased cancer risk for alcoholics with either ADH2*1/2*1 (OR = 2.03) or ALDH2*1/2*2 (OR = 12.76). For those having ADH2*1/2*1 combined with ALDH2*1/2*2, the esophageal cancer risk was enhanced in a multiplicative fashion (OR = 27.66). Responses to flushing questions showed that only 47.8% of the ALDH2*1/2*2 hetcrozygotes with ADH2*1/2*1, compared with 92.3% of those with ALDH2*l/2*2 and the ADH2*2 allele, reported current or former flushing. Genotyping showed that for alcoholics who reported ever flushing, the questionnaire was 71.4% correct in identifying ALDH2*1/2*2 and 87.9% correct in identifying ALDH2*1/2*1. Conclusion: Japanese alcoholics can be divided into cancer susceptibility groups on the basis of their combined ADH2 and ALDH2 genotypes. The flushing questionnaire can predict high risk ALDH2*1/2*2 fairly accurately in persons with ADH2*2 allele, but a reliable screening procedure for the highest risk gene combination (ADH2*1/2*1 and ALDH2*1/2*2) will require further investigation.

KW - Alcohol Dehydrogenase

KW - Alcoholism

KW - Aldehyde Dehydrogenase

KW - Esophageal Cancer

KW - Flushing Response

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