ALCOHOL AND GASTROINTESTINAL CANCER - PATHOGENIC MECHANISMS

Chronic heavy alcohol consumption leads to a significantly increased r isk of cancer in the oropharynx, larynx and the oesophagus. In the liv er, chronic alcohol abuse results in cirrhosis, a precursor of hepatoc ellular cancer. More recent epidemiologic studies also demonstrate tha t regular alcohol consumption, even in low amounts, has an enhanced ri sk for rectal cancer and cancer of the breast. Alcohol by itself is no t a carcinogen. However, alcohol can increase the susceptibility of va rious organs to chemical carcinogens by a variety of mechanisms. Among these, increased activation of procarcinogens through microsomal enzy me induction, a change in the metabolism and/or distribution of carcin ogens, interference with the system that repairs carcinogen-induced DN A alkylations, direct mucosal tissue damage with consecutive stimulati on of cellular regeneration and alcohol-mediated malnutrition may be o f importance. In the upper gastrointestinal tract the production of ac etaldehyde and free radicals via cytochrome P450 2E1 and via alcohol d ehydrogenase may lead to tissue damage and to secondary hyper-regenera tion. In addition, local mechanisms may also be involved in the co-car cinogenic process. In the rectal mucosa acetaldehyde seems to be an im portant factor in carcinogenesis and may be predominantly produced by faecal bacteria.