Alcohol and Cancer

Chapter

Abstract

Alcohol is a major risk factor for a variety of cancer sites including the upper gastrointestinal tract (oropharynx, oesophagus), the larynx, the colorectum, the liver, and the female breast. In animal experiments ethanol and acetaldehyde, the first metabolites of ethanol oxidation, are both carcinogenic. Acetaldehyde can bind to DNA forming various DNA adducts, some of them with high carcinogenic potential. Indeed, individuals with an increased accumulation of acetaldehyde due to changes in ethanol- or acetaldehyde metabolism have an increased cancer risk when they drink chronically. This includes individuals with a genetically determined increased acetaldehyde production due to alcohol dehydrogenase polymorphism and those with a decreased detoxification of acetaldehyde due to an acetaldehyde dehydrogenase mutation. In addition, oral bacterial overgrowth due to poor oral hygiene also increases salivary acetaldehyde, since bacteria and yeasts are capable to generate acetaldehyde from ethanol. Dietary deficiencies such as a lack of folate, riboflavine, and zinc may also contribute to the increased cancer risk in the alcoholic. It is of considerable importance that smoking and drinking act synergistically. Smoking increases the acetaldehyde burden following alcohol consumption since smoke itself contains acetaldehyde and drinking enhances the activation of various procarcinogens present in tobacco smoke due to increased metabolic activation by induction of the cytochrome P-4502E1 (CYP2E1)-dependent microsomal biotransformation system in the mucosa of the upper digestive tract and the liver. The induction of CYP2E1 by chronic ethanol consumption also results in the production of reactive oxygen species during ethanol metabolism via CYP2E1, and these oxygen species lead to lipid peroxidation. Lipid peroxidation products such as 4-hydroxynonenal can then bind to DNA, forming highly mutagenic and carcinogenic exocyclic etheno-DNA adducts. Subsequently, chronic ethanol ingestion results in severe alterations of the methyl transfer with hypomethylation of DNA and also in a decrease of retinoic acid concentrations associated with the activation of protooncogenes and hyperproliferation. All these mechanisms functioning in concert stimulate carcinogenesis and the intensity of the effect of various mechanisms may depend among others on tissue sensibility and susceptibility which is determined genetically and/or by the environment.

Keywords

Fermentation Hepatitis Glutathione NADPH Methionine 

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Medicine and Center of Alcohol Research, Liver Disease and Nutrition, Salem Medical CenterUniversity of HeidelbergHeidelbergGermany

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