Genetic Polymorphisms of ADH1B, ADH1C and ALDH2, Alcohol Consumption, and the Risk of Gastric Cancer: The Japan Public Health Center-based Prospective Study

Carcinogenesis. 2015 Feb;36(2):223-31. doi: 10.1093/carcin/bgu244. Epub 2014 Dec 18.

Abstract

The association between alcohol consumption, genetic polymorphisms of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) and gastric cancer risk is not completely understood. We investigated the association between ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms, alcohol consumption and the risk of gastric cancer among Japanese subjects in a population-based, nested, case-control study (1990-2004). Among 36 745 subjects who answered the baseline questionnaire and provided blood samples, 457 new gastric cancer cases matched to 457 controls were used in the analysis. The odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated using logistic regression models. No association was observed between alcohol consumption, ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms and gastric cancer risk. However, considering gene-environmental interaction, ADH1C G allele carriers who drink ≥150 g/week of ethanol had a 2.5-fold increased risk of gastric cancer (OR = 2.54, 95% CI = 1.05-6.17) relative to AA genotype carriers who drink 0 to <150 g/week (P for interaction = 0.02). ALDH2 A allele carriers who drink ≥150 g/week also had an increased risk (OR = 2.08, 95% CI = 1.05-4.12) relative to GG genotype carriers who drink 0 to < 150 g/week (P for interaction = 0.08). To find the relation between alcohol consumption and gastric cancer risk, it is important to consider both alcohol consumption level and ADH1C and ALDH2 polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alcohol Dehydrogenase / genetics*
  • Alcohol Drinking / epidemiology*
  • Alcohol Drinking / genetics
  • Aldehyde Dehydrogenase / genetics*
  • Aldehyde Dehydrogenase, Mitochondrial
  • Case-Control Studies
  • Ethanol / administration & dosage
  • Ethanol / adverse effects*
  • Female
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Risk
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / genetics*
  • Surveys and Questionnaires

Substances

  • Ethanol
  • ADH1B protein, human
  • ADH1C protein, human
  • Alcohol Dehydrogenase
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase
  • Aldehyde Dehydrogenase, Mitochondrial