Alcohol and cancer: genetic and nutritional aspects.
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 alcohol-associated 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 alcohol-induced 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.
Pöschl
Gudrun
G
Laboratory of Alcohol Research, Liver Disease and Nutrition and Department of Medicine, Salem Medical Center, Zeppelinstrasse 11-33, 69121 Heidelberg, Germany.
Stickel
Felix
F
Wang
Xiang D
XD
Seitz
Helmut K
HK
D000079:Acetaldehyde / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000437:Alcoholism / Q000150:complications* / Q000235:genetics*; D002273:Carcinogens / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005494:Folic Acid Deficiency / Q000150:complications; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D009747:Nutritional Physiological Phenomena; D017382:Reactive Oxygen Species / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000150:complications
D002273:Carcinogens; D017382:Reactive Oxygen Species; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D000079:Acetaldehyde