Alcohol and gastrointestinal cancer: pathogenic mechanisms

Chronic heavy alcohol consumption leads to a significantly increased risk of cancer in the oropharynx, larynx and the oesophagus. In the liver, chronic alcohol abuse results in cirrhosis, a precursor of hepatocellular cancer. More recentepidemiologic studies also demonstrate that regular alcohol consumption, even in low amounts, has an enhanced risk for rectal cancer and cancer of the breast. Alcohol by itself is not a carcinogen. However, alcohol can increase the susceptibility of various organs to chemical carcinogens by a variety of mechanisms. Among these, increased activation of procarcinogens through microsomal enzyme induction, a change in the metabolism and/or distribution of carcinogens, interference with the system that repairs carcinogen-induced DNA alkylations, direct mucosal tissue damage with consecutive stimulation of cellular regeneration and alcohol-mediated malnutrition may be of importance. In the upper gastrointestinal tract the production of acetaldehyde and free radicals via cytochrome P450 2E1 and via alcohol dehydrogenase may lead to tissue damage and to secondary hyper-regeneration. In addition, local mechanisms may also be involved in the co-carcinogenic process. In the rectal mucosa acetaldehyde seems to be an important factor in carcinogenesis and may be predominantly produced by faecal bacteria.