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 well-accepted recreational drug, 26.4% of all lip and oral cavity cancers worldwide are related to heavy drinking. 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.

The Complexity of Tobacco Smoke-Induced Mutagenesis in Head and Neck Cancer

“…In this regard, we also identified mutagenic processes linked to alcohol exposure 13,16 , including signatures SBS16, ID11, and an unreported association with signature DBS4. In HNC, alcohol-related signatures were predominantly observed in patients reporting both alcohol and tobacco consumption, reflecting the synergistic effect between these two factors on disease risk 9,41 .…”

The Potential Association between E2F2, MDM2 and p16 Protein Concentration and Selected Sociodemographic and Clinicopathological Characteristics of Patients with Oral Squamous Cell Carcinoma

“…Other risk factors include air pollution, UV exposure and viral infections. Another potential group of risk factors is related to endogenous factors, such as genetic predisposition, including abnormalities in proliferation, apoptosis, differentiation, signal transduction, angiogenesis, cell cycle regulation and DNA repair [ 2 , 3 , 4 , 5 , 6 ]. E2F transcription factor 2 (E2F2), murine double minute (2 MDM2) and p16 (also known as cyclin-dependent kinase inhibitor 2A, CDKN2A) are some of the key proteins involved in the control of the cell cycle [ 7 , 8 , 9 ].…”

Structure‐based study to identify alkaloids as promising cytochrome P450 (CYP1A1) inhibitors: An in silico approach using virtual screening, molecular dynamic simulations, and binding free energy calculation

“…9 Several studies suggest that tobacco consumption and alcohol abuse are the main contributors to OSCC. [12][13][14] The noncombustible forms of tobacco (smokeless tobacco [SLT] products) are popularly consumed in India and attributed to oral carcinogenesis. 15 SLT contains several carcinogens like TSNAs including N′-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N′-nitrosoanabasine (NAB), 4-(methylnitrosamino)-1-(3pyridyl)-1-butanol (NNAL), N′-nitrosoanatabine (NAT), PAHs, N-nitrosamine acids, and many others.…”

“…Several studies suggest that tobacco consumption and alcohol abuse are the main contributors to OSCC 12–14 . The noncombustible forms of tobacco (smokeless tobacco [SLT] products) are popularly consumed in India and attributed to oral carcinogenesis 15 .…”