Genetic Polymorphism in Alcohol Metabolism and Drinking Behavior Are Associated with Gastric Cancer Risk in Men

Intern Med. 2025 Jan 1;64(1):41-46. doi: 10.2169/internalmedicine.3159-23. Epub 2024 May 9.

Abstract

Objective In recent years, there has been a growing focus on health risks associated with alcohol consumption. The present study investigated whether or not the genetic variant of aldehyde dehydrogenase 2 (ALDH2) influences the risk of gastric cancer among individuals identified as hazardous drinkers using the Alcohol Use Disorders Identification Test (AUDIT), which provides a comprehensive assessment of hazardous drinking behavior. Patients We enrolled men with hazardous drinking behavior (AUDIT score ≥8) who had undergone gastric cancer screening (either endoscopy or a barium X-ray examination of the upper gastrointestinal tract) between April 2013 and March 2020 within 1 year from entry and who had subsequently undergone at least one more gastric cancer screening up to March 2021. Functional single-nucleotide polymorphisms of ALDH2 (rs671) were measured using a direct TaqMan polymerase chain reaction method with unprocessed saliva. Results A total of 246 men were enrolled, comprising 193 individuals with active ALDH2 (ALDH2*1/*1) and 53 with less-active ALDH2 (ALDH2*1/*2). The cumulative incidence of gastric cancer in the less-active group was higher than in the active ALDH2 group (p=0.01, hazard ratio: 4.6, 95% confidence interval: 1.2-16.7). Alcohol consumption was lower in the less-active ALDH2 group than in the active ALDH2 group, although no marked difference was observed in the AUDIT score. Conclusion In individuals with hazardous drinking behavior, a heightened risk of gastric cancer was observed among those with less-active ALDH2 variants, even when their alcohol consumption was comparatively lower than in those with active ALDH2 variants.

Keywords: ALDH2; alcohol use disorders identification test; gastric cancer; hazardous drinking.

MeSH terms

  • Aged
  • Alcohol Drinking* / adverse effects
  • Alcohol Drinking* / genetics
  • Aldehyde Dehydrogenase, Mitochondrial* / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Stomach Neoplasms* / epidemiology
  • Stomach Neoplasms* / genetics

Substances

  • Aldehyde Dehydrogenase, Mitochondrial
  • ALDH2 protein, human