Multiple primary esophageal and concurrent upper aerodigestive tract cancer and the aldehyde dehydrogenase-2 genotype of Japanese alcoholics

Cancer. 1996 May 15;77(10):1986-90. doi: 10.1002/(SICI)1097-0142(19960515)77:10<1986::AID-CNCR4>3.0.CO;2-F.


Background: Multiple intraesophageal primary cancer and upper aerodigestive tract (UADT) cancer associated with esophageal cancer are common diseases, especially in heavy drinkers. They are often explained by the concept of field cancerization, which suggests a similar etiology. However, little is known about the nature of the hypothesized etiology.

Methods: Among 901 Japanese male alcoholics systematically screened by upper gastrointestinal endoscopy (with esophageal iodine staining), 33 had squamous cell carcinoma of the esophagus. The multiplicity of their esophageal carcinoma and their concurrent UADT cancer was compared with their genotype for aldehyde dehydrogenase-2 (ALDH2), the major determinant of blood acetaldehyde concentration after drinking.

Results: Of 17 patients with inactive ALDH2, 13 (76.5%) had multiple primary carcinoma of the esophagus, whereas 5 of 16 (31.3%) with active ALDH2 had multiple carcinomas (P < 0.01). The prevalence of concurrent UADT cancer was 29.4% in those patients with inactive ALDH2, compared with 6.3% in those patients with active ALDH2.

Conclusions: Inactive ALDH2 is a risk factor for multiple carcinoma of the esophagus in alcoholics. Acetaldehyde, a recognized animal carcinogen, appears to play a critical role in field cancerization.

Publication types

  • Comparative Study

MeSH terms

  • Alcoholism / complications*
  • Aldehyde Dehydrogenase / genetics*
  • Aldehyde Dehydrogenase, Mitochondrial
  • Base Sequence
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / pathology
  • Esophageal Neoplasms / etiology*
  • Esophageal Neoplasms / pathology
  • Genotype
  • Gingival Neoplasms / etiology
  • Humans
  • Hypopharyngeal Neoplasms / etiology
  • Japan / ethnology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasms, Multiple Primary / etiology*
  • Neoplasms, Multiple Primary / pathology
  • Polymerase Chain Reaction
  • Stomach Neoplasms / etiology


  • ALDH2 protein, human
  • Aldehyde Dehydrogenase
  • Aldehyde Dehydrogenase, Mitochondrial