Alcohol consumption and cancer of the gastrointestinal tract.
Epidemiological data have identified chronic alcohol consumption as a significant risk factor for upper gastrointestinal cancer (oropharynx, hypopharynx, esophagus) and colorectal cancer. Pathophysiological mechanisms include generation of acetaldehyde (AA) and reactive oxygen species (ROS), induction of cytochrome P 4502E1 (CYP2E1), and local and nutritional factors. Genetic polymorphisms of alcohol-metabolizing enzymes may individually influence the risk of carcinogenesis. AA, the first and major metabolite of ethanol, has proven to be the most carcinogenic and mutagenic agent in alcohol-associated cancer. Gastrointestinal bacteria as well as various isozymes of alcohol dehydrogenase (ADH) are capable of metabolizing ethanol to AA thus leading to an increased cell turnover of the gastrointestinal mucosa after chronic alcohol consumption. In Caucasians, ADH1C polymorphism is most important, for the ADH1C*1 transcription results in an ADH isoenzyme 2.5 times more active than that from ADH1C*2, which is associated with an increase in AA production. Additionally, oxidative stress due to an induction of CYP2E1 in the gastrointestinal mucosa of alcoholics should be considered as another key factor in alcohol-induced carcinogenesis. Nutritional deficiencies, i.e. lack of folic and retinoic acid, as well as malnutrition itself may also contribute to the development of gastrointestinal cancer.
Seitz
Helmut K
HK
Department of Medicine, Salem Medical Centre and Laboratory of Alcohol Research, Liver Disease and Nutrition, Heidelberg, Germany. helmut_karl.seitz@urz.uni-heidelberg.de
Maurer
Britta
B
Stickel
Felix
F
D000428:Alcohol Drinking / Q000009:adverse effects*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D015995:Prevalence; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis
D019392:Cytochrome P-450 CYP2E1; D000444:Aldehyde Dehydrogenase