Alcohol and cancer: genetic and nutritional aspects

Abstract

Chronic alcohol consumption is a major risk factor for cancer of upper aero-digestive tract (oro-pharynx, hypopharynx, larynx and oesophagus), the liver, the colo-rectum and the breast. Evidence has accumulated that acetaldehyde is predominantly responsible for alcoholassociated carcinogenesis. Acetaldehyde is carcinogenic and mutagenic, binds to DNA and protein, destroys the folate molecule and results in secondary cellular hyper-regeneration. Acetaldehyde is produced by mucosal and cellular alcohol dehydrogenase, cytochrome P450 2E1 and through bacterial oxidation. Its generation and/or its metabolism is modulated as a result of polymorphisms or mutations of the genes responsible for these enzymes. Acetaldehyde can also be produced by oral bacteria. Smoking, which changes the oral bacterial flora, also increases salivary acetaldehyde. Cigarette smoke and some alcoholic beverages, such as Calvados, contain acetaldehyde. In addition, chronic alcohol consumption induces cytochrome P450 2E1 enxyme activity in mucosal cells, resulting in an increased generation of reactive oxygen species and in an increased activation of various dietary and environmental carcinogens. Deficiencies of riboflavin, Zn, folate and possibly retinoic acid may further enhance alcohol-associated carcinogenesis. Finally, methyl deficiency as a result of multiple alcoholinduced changes leads to DNA hypomethylation. A depletion of lipotropes, including methionine, choline, betaine and S-adenosylmethionine, as well as folate, results in the hypomethylation of oncogenes and may lead to DNA strand breaks, all of which are associated with increased carcinogenesis.Chronic alcohol consumption: Cancer: Acetaldehyde: Cytochrome P450 2E1:Alcohol-nutrient interactionsChronic excessive alcohol consumption is a strong risk factor for cancer of the upper aero-digestive tract (oral cavity, pharynx, hypopharynx, larynx, oesophagus), the liver, the colo-rectum and the breast. A great number of epidemiological studies have demonstrated the correlation between alcohol ingestion and the occurrence of cancer in these organs . These studies clearly show that the ingestion of all types of alcoholic beverage is associated with an increased cancer risk, which suggests that ethanol is the common ingredient that causes this effect. The exact mechanism of ethanol-associated carcinogenesis has remained obscure, since ethanol is not a carcinogen. Multiple mechanisms are involved in alcoholassociated cancer development, including the effect of acetaldehyde (AL; the first metabolite of ethanol oxidation), the induction of cytochrome P450 2E1 (CYP2E1) leading to the generation of reactive oxygen species and enhanced procarcinogen activation, modulation of cellular regeneration and nutritional deficiencies. These mechanisms have been the subject of recent reviews ). In the present paper major emphasis is given to the most recent observations contributing to the elucidation of the mechanisms involved in alcohol-associated carcinogenesis, such as genetic factors and alcohol-nut...

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