Interrelationship between alcohol, smoking, acetaldehyde and cancer.
In industrialized countries alcohol and tobacco are the main risk factors of upper digestive tract cancer. With regard to the pathogenesis of these cancers, there is strong epidemiological, biochemical and genetic evidence supporting the role of the first metabolite of alcohol oxidation--acetaldehyde--as a common denominator. Alcohol is metabolized to acetaldehyde locally in the oral cavity by microbes representing normal oral flora. Poor oral hygiene, heavy drinking and chronic smoking modify oral flora to produce more acetaldehyde from ingested alcohol. Also, tobacco smoke contains acetaldehyde, which during smoking becomes dissolved in saliva. Via swallowing, salivary acetaldehyde of either origin is distributed from oral cavity to pharynx, oesophagus and stomach. Strongest evidence for the local carcinogenic action of acetaldehyde provides studies with ALDH2-deficient Asian drinkers, who form an exceptional human model for long-term acetaldehyde exposure. After drinking alcohol they have an increased concentration of acetaldehyde in their saliva and this is associated with over 10-fold risk of upper digestive tract cancers. In conclusion, acetaldehyde derived either from ethanol or tobacco appears to act in the upper digestive tract as a local carcinogen in a dose-dependent and synergistic way.
Salaspuro
Mikko
M
Research Unit of Substance Abuse Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
D000079:Acetaldehyde / Q000633:toxicity*; D000428:Alcohol Drinking / Q000009:adverse effects*; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism; D004067:Digestive System Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D000431:Ethanol / Q000378:metabolism* / Q000633:toxicity; D005285:Fermentation; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012463:Saliva / Q000378:metabolism / Q000382:microbiology; D012907:Smoking / Q000009:adverse effects*
D000431:Ethanol; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde