title: A local mechanism by which alcohol consumption causes cancer.
abstract: Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not clear why alcohol use preferentially exerts a local carcinogenic effect. It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages; however, this effect may have been overlooked because dead cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells. Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of DNA-damaging agents (e.g., acetaldehyde and tobacco carcinogens). Alcohol consumption may increase the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis. Understanding the mechanisms of carcinogenicity of alcohol is important to reinforce the epidemiological evidence and to raise public awareness of the strong link between alcohol consumption and cancer.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain. Electronic address: mlopezlazaro@us.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Lázaro
mesh_terms: D000428:Alcohol Drinking; D006801:Humans; D009369:Neoplasms / Q000209:etiology*
keywords: Alcohol; Cancer; Carcinogenesis; Esophagus; Ethanol; Oral cavity; Pharynx; Stem cells; Synergism; Tobacco