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Interaction of Alcohol and Tobacco in Upper Aerodigestive Tract and Stomach CancerSalaspuro M.a · Salaspuro V.a · Seitz H.b
aResearch Unit of Substance Abuse Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; bDepartment of Medicine, Salem Medical Center Heidelberg and Laboratory of Alcohol Research, Liver Disease and Nutrition, Heidelberg, Germany
There is increasing epidemiological, biochemical, and genetic evidence supporting the role of the first metabolite of alcohol oxidation - acetaldehyde - as a common denominator in the pathogenesis of upper aerodigestive tract cancers. Accordingly, acetaldehyde derived either from ethanol or tobacco appear to act in the digestive tract as a local carcinogen in a dose-dependent and synergistic way. Alcohol is metabolized to acetaldehyde locally in the oral cavity mainly by microbes representing normal oral flora. Also tobacco smoke contains high levels of acetaldehyde, which during smoking is dissolved in the saliva. Via swallowing salivary acetaldehyde of either origin will be distributed further to the pharynx, esophagus, and stomach. However, strongest evidence for the local carcinogenic action of acetaldehyde provide biochemical studies with individuals who have either a decreased ability to detoxify acetaldehyde or an enhanced ability to produce it. ALDH2-deficient Asian heavy drinkers and Caucasian alcoholics homozygous for the fast ADH1C*1 allele have markedly increased risk for aerodigestive tract cancers. Both of these groups also have markedly higher salivary acetaldehyde levels after drinking of alcohol than in those with the normal enzymes. In affected individuals the cells of the salivary glands and/or mucous membranes, obviously contribute in addition to the microbes to the local production of acetaldehyde in the saliva. On this basis, these genetic variants form an exceptional human model for long-term acetaldehyde exposure. With regard to cancer prevention, it is important to characterize all those factors that regulate the concentration of acetaldehyde in the upper aerodigestive tract. In addition to the hereditary factors, these include smoking and drinking habits, individual differences in the gut microflora, salivary ethanol levels, and some acetaldehyde-binding agents.