High salivary acetaldehyde after a moderate dose of alcohol in ALDH2-deficient subjects: Strong evidence for the local carcinogenic action of acetaldehyde

Background: Due to a point mutation, aldehyde dehydrogenase-2 (ALDH2) isoen zyme is deficient in 30% to 50% of Asians. Among Asian ALDH2-deficient heav y drinkers, the risk for digestive tract cancers is markedly increased (odd s ratio 3.4-54.2). The reason for this is unknown but could be due to the l ocal carcinogenic action of acetaldehyde. Methods: Salivary and blood acetaldehyde levels were determined in 20 healt hy Asians after a moderate dose of alcohol (0.5 g/kg of body weight). Saliv ary acetaldehyde production capacity from ethanol in vitro was measured als o. ALDH2 genotype of the Asians was determined from isolated leukocyte-deox yribonucleic acid by polymerase chain reaction/restriction fragment length polymorphism method. Acetaldehyde content of parotid gland saliva was measu red in three ALDH2-deficient Asians and three White subjects with normal AL DH2 after the same dose of ethanol. Results: Seven of the Asians were heterozygous for the mutant ALDH2*2 allel e (flushers). They had two to three times higher salivary acetaldehyde leve ls than the Asians (n = 13) with normal ALDH2 throughout the follow-up peri od of 240 min (p < 0.001). Only in the flushers did the parotid gland contr ibute 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 acetaldehyd e removal, we found that in addition to oral microflora, acetaldehyde in sa liva may also originate from the oxidation of ethanol in the parotid gland. When combined with earlier epidemiological data, these results offer a str ong evidence for the local carcinogenic action of acetaldehyde in humans.