Association of Oral Cancers With Alcohol Consumption: Exploring Mechanisms

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Cancer results from a series of genetic and epigenetic changes that can occur via multiple pathways. Genetic changes can be inherited, but most individuals do not inherit these changes. Instead, they inherit genes that make their cells more or less susceptible to acquiring and maintaining such changes through mechanisms such as carcinogen metabolism (activation and detoxification), DNA repair proficiency, or immune function; nongenetic factors, such as nutritional components, may also affect this susceptibility. It is within this milieu that environmental agents cause cancer.

In this issue of the Journal, two groups of investigators ( 1 , 2 ) examine underlying mechanisms and cofactors of an environmental cause of oral cancers—alcohol. Oral cavity and pharyngeal cancers are strongly associated with tobacco and alcohol use ( 3 , 4 ). The explanation for increased cancer risk associated with increasing alcohol consumption is not complete ( 4 ), but it is believed to be due, at least in part, to the carcinogenic effect of the first metabolite of ethanol, acetaldehyde. Alcohol dehydrogenases metabolize ethanol to acetaldehyde, which is then metabolized to acetate by aldehyde dehydrogenases. The focus of these investigators ( 1 , 2 ) is on factors that affect the metabolism of ethanol to acetaldehyde, a carcinogen. Harty et al. ( 1 ) assessed the association between oral cancers and variation in the gene coding for alcohol dehydrogenase type 3 (ADH ₃ ) among humans; using a rat model, Homann et al. ( 2 ) assessed the effects of acetaldehyde on the upper gastrointestinal tract mucosa to provide support for the impact of bacterial metabolism of alcohol on oral cancer risk.