Ethanol-Induced Cell Damage Can Result in the Development of Oral Tumors
Abstract
Alcohol consumption is an underestimated risk factor for the development of precancerous lesions in the oral cavity. Although alcohol is a [widely used] recreational drug, 26.4% of all lip and oral cavity cancers worldwide are related to heavy [alcohol use]. Molecular mechanisms underlying this carcinogenic effect of ethanol are still under investigation.
An important damaging effect comes from the first metabolite of ethanol, being acetaldehyde. Concentrations of acetaldehyde detected in the oral cavity are relatively high due to the metabolization of ethanol by oral microbes. Acetaldehyde can directly damage the DNA by the formation of mutagenic DNA adducts and interstrand crosslinks.
Additionally, ethanol is known to affect epigenetic methylation and acetylation patterns, which are important regulators of gene expression. Ethanol-induced hypomethylation can activate the expression of oncogenes which subsequently can result in malignant transformation.
The recent identification of ethanol-related mutational signatures emphasizes the role of acetaldehyde in alcohol-associated carcinogenesis. However, not all signatures associated with alcohol intake also relate to acetaldehyde. This finding highlights that there might be other effects of ethanol yet to be discovered.
Simplified summary
Despite the fact that alcohol causes lip and oral cavity cancers, the exact molecular mechanisms by which ethanol – the chemical in alcohol – damages cells are still under investigation. The metabolism of ethanol plays a significant role.
When ethanol is metabolized it creates reactive metabolites called acetaldehyde, that can directly damage the DNA. If the damage is repaired incorrectly, mutations can be fixed in the DNA sequence. When mutations affect key regulatory genes, for example genes which regulate the cell cycle it can cause uncontrolled cell growth.
Recently, global patterns of mutations have been identified. These so-called mutational signatures represent a fingerprint of the different mutational processes over time. Interestingly, there were ethanol-related signatures discovered that did not associate with ethanol metabolism. This finding highlights there might be other molecular effects of ethanol that are yet to be discovered.
