Alcohol-induced epigenetic changes in cancer. - GreenMedInfo Summary

Chronic, heavy alcohol consumption is associated with serious negative health effects, including the development of several cancer types. One of the pathways affected by alcohol toxicity is the one-carbon metabolism. The alcohol-induced impairment of this metabolic pathway results in epigenetic changes associated with cancer development. These epigenetic changes are induced by folate deficiency and by products of the ethanol metabolism. The changes induced by long-term heavy ethanol consumption result in elevations of homocysteine and S-adenosyl-homocysteine (SAH) and reductions in S-adenosylmethionine (SAM) and antioxidant glutathione (GSH) levels, leading to abnormal promoter gene hypermethylation, global hypomethylation, and metabolic insufficiency of antioxidant defense mechanisms. In addition, reactive oxygen species (ROS) generated during the ethanol metabolism induce alterations in DNA methylation patterns that play a critical role in cancer development. Specific epigenetic changes in esophageal, hepatic, and colorectal cancers have been detected in blood samples and proposed to be used clinically as epigenetic biomarkers for diagnosis and prognosis of these cancers. Also, genetic variants of genes involved in one-carbon metabolism and ethanol metabolism were found to modulate the relationship between alcohol-induced epigenetic changes and cancer risk. Furthermore, alcohol metabolism products have been associated with an increase in NADH levels, which lead to histone modifications and changes in gene expression that in turn influence cancer susceptibility. Chronic excessive use of alcohol also affects selected members of the family of microRNAs, and as miRNAs could act as epigenetic regulators, this may play an important role in carcinogenesis. In conclusion, targeting alcohol-induced epigenetic changes in several cancer types could make available clinical tools for the diagnosis, prognosis, and treatment of these cancers, with an important role in precision medicine.