A narrative review on alcohol and alimentary tract cancer with special emphasis on acetaldehyde and oxidative stress.

Approximately 4% of all cancer cases worldwide are caused by alcohol consumption (oropharynx, larynx, esophagus, stomach, colorectum, liver and the female breast). Various mechanisms contribute to ethanol-mediated carcinogenesis, including the action of acetaldehyde, the first metabolite of ethanol oxidation and oxidative stress primarily promoted through the induction of cytochrome P4502E1. Acetaldehyde is toxic and carcinogenic, binds to DNA and proteins, inhibits the oxidative defense- and the nuclear repair system, and prevents DNA methylation. High levels of acetaldehyde occur through increased production in the presence of a hyperactive alcohol dehydrogenase (ADH1C*1,1) or decreased degradation in the presence of low active aldehyde dehydrogenase (ALDH2*1,2). In addition, microbes of the upper alimentary tract and the colorectum effectively produce acetaldehyde from ethanol. In addition, ethanol induces cytochrome P4502E1 resulting in an enhanced ethanol metabolism and the generation of reactive oxygen species (ROS). ROS may cause lipid peroxidation (LPO) with the LPO-products 4-hydroxynonenal or malondialdehyde, which may form highly carcinogenic etheno DNA-adducts CYP2E1 is also involved in the activation of a variety of dietary and tobacco procarcinogens and in the degradation of retinoic acid. Alcohol also influences tumor promotion, such as epigenetics with a change in DNA methylation and histone modification, and affects a variety of cancer genes and signaling pathways. Preventive measures include reducing alcohol consumption, quitting smoking and keeping good oral hygiene. Alcohol consumers - especially when they smoke or belong to genetic risk groups - should be regularly checked for cancer of the upper alimentary tract, for alcohol- associated liver disease, and for breast cancer. Cessation or reduction of alcohol consumption definitively reduces cancer risk.