Researchers have demonstrated how alcohol damages mouse stem cell DNA in a new study, helping to explain why drinking can increase cancer risk [1]. The study was published in the journal Nature on January 3.

There have been multiple cell culture studies looking at how alcohol promotes cancer, but this study used mice to show how alcohol can cause permanent damage to DNA.

Alcohol can cause permanent genetic damage

The research team from the MRC Laboratory of Molecular Biology, Cambridge, gave diluted ethanol to mice. They then examined chromosomes and DNA to see what genetic damage was caused by acetaldehyde, a toxic chemical that is produced when the body processes alcohol.

The researchers discovered that acetaldehyde can break and damage the DNA in hematopoietic (blood) stem cells. This results in rearranged chromosomes and permanent mutations to the DNA sequences in these cells.







Over time, DNA damage, which can give rise to cancer, can and does occur by chance in stem cells. However, this study lets us better understand how alcohol damages the DNA in stem cells further, increasing the risk of developing seven different types of cancer, including mouth, upper throat, laryngeal, oesophageal, breast, liver, and bowel.

Repairing the damage

The body does have ways to protect itself from the damage caused by alcohol. The first line of defense consists of aldehyde dehydrogenases (ALDH) enzymes. These enzymes break down the harmful acetaldehyde into acetate, which our cells can actually use as an energy source. In the study, the researchers tested this with mice that lacked the ALDH enzyme ALDH2, and these mice sustained four times as much stem cell DNA damage compared to normal mice with functional ALDH2 enzymes.

The second line of defense consists of the cellular systems that repair DNA damage. Unfortunately, these repair systems are not perfect and cannot always repair the damage fully; over time, the DNA damage that is not resolved builds up. For some people, in particular people from South East Asia, these repair systems fail to work properly, meaning their cells cannot repair the damage effectively, putting them at increased risk.

Alcohol consumption causes around 12,800 cancer cases each year in the UK. Just one pint of lager or a large glass of wine a day significantly increases the risk of mouth, throat, oesophageal, breast and bowel cancers. However, there is no evidence that drinkers are at an increased risk of blood cancers despite these new findings showing that drinking can alter the DNA in blood stem cells. The blood system has a high level of quality control and disposes of damaged cells, this may explain why alcoholics often become anemic, but other tissues in the body may be more susceptible.







Conclusion

While it should be noted that the amount of alcohol administered to the mice in this study would be a considerable amount in human terms, the World Health Organization does classify alcohol as a Group 1 carcinogen, citing “convincing evidence” it causes cancer in humans. Considering this, it seems wise to avoid excessive consumption of alcohol in the first place.

Literature

[1] Garaycoechea, J, I., et al., Alcohol-derived and endogenous aldehydes damage chromosomes and mutate stem cells. Nature. DOI 10.1038/nature25154.