ALDH2 genotype has no effect on salivary acetaldehyde without the presence of ethanol in the systemic circulation

PLoS One. 2013 Sep 13;8(9):e74418. doi: 10.1371/journal.pone.0074418. eCollection 2013.


Background: Acetaldehyde associated with alcoholic beverages was recently classified as carcinogenic (Group 1) to humans based on uniform epidemiological and biochemical evidence. ALDH2 (aldehyde dehydrogenase 2) deficient alcohol consumers are exposed to high concentrations of salivary acetaldehyde and have an increased risk of upper digestive tract cancer. However, this interaction is not seen among ALDH2 deficient non-drinkers or rare drinkers, regardless of their smoking status or consumption of edibles containing ethanol or acetaldehyde. Therefore, the aim of this study was to examine the effect of the ALDH2 genotype on the exposure to locally formed acetaldehyde via the saliva without ethanol ingestion.

Methods: The ALDH2 genotypes of 17 subjects were determined by PCR-RFLP. The subjects rinsed out their mouths with 5 ml of 40 vol% alcohol for 5 seconds. Salivary ethanol and acetaldehyde levels were measured by gas chromatography.

Results: Acetaldehyde reached mutagenic levels rapidly and the exposure continued for up to 20 minutes. The mean salivary acetaldehyde concentrations did not differ between ALDH2 genotypes.

Conclusions: For ALDH2 deficient subjects, an elevated exposure to endogenously formed acetaldehyde requires the presence of ethanol in the systemic circulation.

Impact: Our findings provide a logical explanation for how there is an increased incidence of upper digestive tract cancers among ALDH2 deficient alcohol drinkers, but not among those ALDH2 deficient subjects who are locally exposed to acetaldehyde without bloodborne ethanol being delivered to the saliva. Thus, ALDH2 deficient alcohol drinkers provide a human model for increased local exposure to acetaldehyde derived from the salivary glands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaldehyde / metabolism*
  • Adult
  • Aldehyde Dehydrogenase / genetics*
  • Aldehyde Dehydrogenase, Mitochondrial
  • Electrophoresis, Agar Gel
  • Environmental Exposure
  • Ethanol / blood*
  • Female
  • Genotype
  • Genotyping Techniques
  • Humans
  • Male
  • Saliva / metabolism*
  • Surveys and Questionnaires
  • Young Adult


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

Grant support

Funding provided by Yrjö Jahnsson Foundation grant number 6234 (AH), Yrjö Jahnsson Foundation grant number 6071 (SV), Sigrid Juselius Foundation grant number 642 (MS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.