Metabolism of ethyl alcohol and the development of cancer

The main metabolic pathway of ethanol elimination occurs in the liver. Ethanol is oxidised by an alcohol dehydrogenase (ADH) to a very toxic acetaldehyde. The aldehyde is converted to acetate by an aldehyde dehydrogenase (ALDH). Studies of animals with genetic predisposition to drink ethanol indicate the relationship between spontaneous drinking of alcohol and its increased metabolism.

Chronic alcohol consumption is significantly related to the risk of developing cancer in the upper gastrointestinal tract (oral cavity and oesophagus) as well as liver, pancreas, and large intestine. Studies show that the carcinogenic effect of alcohol is due to the action of acetaldehyde, which interferes in many places with DNA synthesis, influences DNA repair capacity, and binding to cellular proteins causes cellular dysfunction.

The aldehyde can generate errors of gene replication. Other mechanisms involved in ethanol metabolism are associated with reactive oxygen species (ROS) resulting from induction of cytochrome P4502E1. Reactive oxygen species can directly affect DNA or by lipid oxidation resulting in breaks in the DNA chain.

Both the formation and metabolism of acetaldehyde is modified by ADH and ALDH. Alcohol dehydrogenase activity is significantly higher in tumour tissues than in healthy tissues and is disproportionately higher in relation to ALDH activity. Such enzyme activity may indicate faster alcohol oxidation and significantly reduced removal of acetaldehyde in the case of cancer. As a result of the diminished acetic aldehyde reduction, its concentration may increase in the tumour tissue and thus may potentiate its carcinogenic effect.