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. 2002 Nov;23(11):1851-9. doi: 10.1093/carcin/23.11.1851.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alcohol Dehydrogenase / genetics*
  • Alcohol Drinking / epidemiology*
  • Aldehyde Dehydrogenase / deficiency
  • Aldehyde Dehydrogenase / genetics*
  • Aldehyde Dehydrogenase, Mitochondrial
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / epidemiology*
  • Carcinoma, Squamous Cell / genetics
  • Case-Control Studies
  • Diet* / statistics & numerical data
  • Esophageal Neoplasms / enzymology
  • Esophageal Neoplasms / epidemiology*
  • Esophageal Neoplasms / genetics
  • Flushing / chemically induced
  • Flushing / enzymology
  • Flushing / genetics
  • Fruit
  • Genetic Predisposition to Disease
  • Genotype
  • Glutathione Transferase / genetics*
  • Hot Temperature
  • Humans
  • Isoenzymes / genetics*
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic
  • Risk Factors
  • Smoking / epidemiology*
  • Surveys and Questionnaires
  • Vegetables

Substances

  • Isoenzymes
  • Alcohol Dehydrogenase
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase
  • Aldehyde Dehydrogenase, Mitochondrial
  • Glutathione Transferase
  • glutathione S-transferase M1