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Effects of alcohol and aldehydes on DNA and risk of cancer; potential implications from a study in mice

The authors of this paper, based on an extensive basic scientific experiment in mice, describe the features and mutational landscape of DNA damage caused by acetaldehyde, an endogenous and alcohol-derived metabolite. This damage results in DNA double-stranded breaks that, despite stimulating recombination repair, also cause chromosome rearrangements. Furthermore, the authors identify how the choice of DNA-repair pathway and a stringent p53 response limit the transmission of aldehyde-induced mutations in stem cells.

Forum members considered this to be a well-done series of experiments that add additional data on the effects of aldehyde on cellular damage, which could potentially lead to an increased risk of cancer. While interesting, these results in mice have limited applicability to the effects of alcohol in humans, as the study conditions do not correspond to that found in real life. For example, the levels of ethanol used to elicit the DNA changes were high and alcohol was directly injected into the animals, whereas in humans alcohol is orally absorbed and undergoes several types of metabolism that reduce maximum blood alcohol concentrations achieved. Further, the animal model was based on mice that had been genetically manipulated in that particular genes had been selectively ‘knocked out’ to make them unable to metabolize aldehyde or to repair DNA damage; while this was necessary to study the effects in a basic scientific experiment, it is in contrast to what would occur under non-manipulated conditions of alcohol consumption in humans.

The damages shown in this experiment were to hematologic cells, and epidemiologic studies have generally not found an increase in the risk of hematologic cancers in humans to be associated with alcohol, especially from the moderate intake of alcohol (and many studies show instead a decrease in risk among drinkers). Thus, studies in humans have not provided support for these reported results from mice. Further, Forum members conclude that the polyphenols that are present in wine may play an important role in blocking a carcinogenic effect associated with alcohol intake.

Reference: Garaycoechea JI, Crossan GP, Langevin F, Mulderrig L, Louzada S, Yang F, Guilbaud G, Park N, Roerink S, Nik-Zainal S, Stratton MR, Patel1 KJ. Alcohol and endogenous aldehydes damage chromosomes and mature stem cells. Nature 2017;553:171-177. doi:10.1038/nature25154.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.
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