High Salivary Acetaldehyde After a Moderate Dose of Alcohol in ALDH2-deficient Subjects: Strong Evidence for the Local Carcinogenic Action of Acetaldehyde

Alcohol Clin Exp Res. 2000 Jun;24(6):873-7.


Background: Due to a point mutation, aldehyde dehydrogenase-2 (ALDH2) isoenzyme is deficient in 30% to 50% of Asians. Among Asian ALDH2-deficient heavy drinkers, the risk for digestive tract cancers is markedly increased (odds ratio 3.4-54.2). The reason for this is unknown but could be due to the local carcinogenic action of acetaldehyde.

Methods: Salivary and blood acetaldehyde levels were determined in 20 healthy Asians after a moderate dose of alcohol (0.5 g/kg of body weight). Salivary acetaldehyde production capacity from ethanol in vitro was measured also. ALDH2 genotype of the Asians was determined from isolated leukocyte-deoxyribonucleic acid by polymerase chain reaction/restriction fragment length polymorphism method. Acetaldehyde content of parotid gland saliva was measured in three ALDH2-deficient Asians and three White subjects with normal ALDH2 after the same dose of ethanol.

Results: Seven of the Asians were heterozygous for the mutant ALDH2*2 allele (flushers). They had two to three times higher salivary acetaldehyde levels than the Asians (n = 13) with normal ALDH2 throughout the follow-up period of 240 min (p < 0.001). Only in the flushers did the parotid gland contribute to salivary acetaldehyde production. The in vitro capacity of saliva to produce acetaldehyde from ethanol was equal in both groups. The flushers' blood acetaldehyde levels were only one ninth of the levels in saliva.

Conclusions: By using this human "knockout model" for deficient acetaldehyde removal, we found that in addition to oral microflora, acetaldehyde in saliva may also originate from the oxidation of ethanol in the parotid gland. When combined with earlier epidemiological data, these results offer a strong evidence for the local carcinogenic action of acetaldehyde in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaldehyde / metabolism*
  • Adult
  • Aldehyde Dehydrogenase / deficiency*
  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase, Mitochondrial
  • Central Nervous System Depressants / blood
  • Central Nervous System Depressants / pharmacology*
  • China / ethnology
  • Digestive System Neoplasms / chemically induced
  • Ethanol / blood
  • Ethanol / pharmacology*
  • Female
  • Humans
  • Japan / ethnology
  • Linear Models
  • Male
  • Mongolia / ethnology
  • Parotid Gland / drug effects
  • Parotid Gland / metabolism
  • Saliva / drug effects*
  • Saliva / metabolism


  • Central Nervous System Depressants
  • Ethanol
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase
  • Aldehyde Dehydrogenase, Mitochondrial
  • Acetaldehyde