Effects of ethanol and acetaldehyde on multi-organ genomic mutation landscapes - PubMed

4 hours ago

Alcohol consumption, especially through its metabolite acetaldehyde, is a major cancer risk factor, notably for head and neck cancers.
The study analyzed genome-wide mutation patterns in rats chronically exposed to ethanol or acetaldehyde, focusing on tumors in the head-and-neck, forestomach, and liver.
Mutational signature SBS17 appeared early and was associated with exposure in about 38% of head-and-neck tumors, suggesting inflammation and oxidative damage as possible mechanisms.
Tumors in exposed rats showed enrichment of driver-like mutations in genes like Tp53, Mtor, and Hras, with all Tp53-mutated tumors being SBS17-positive.
Other mutation types (doublet-base, indel, copy number, structural variants) were sporadic and not specifically linked to exposure.
Previously known alcohol-related mutational signatures in humans (e.g., SBS16, DBS4, ID11) were not observed in the exposed animals.
The findings indicate that alcohol-related carcinogenesis across multiple organs in this model is unlikely driven primarily by direct mutagenicity, but rather by non-mutational processes.
The relationship between SBS17 and TP53 loss-of-function mutations warrants further investigation as potential biomarkers for alcohol-related carcinogenesis.

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