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Experts identify how alcohol raises cancer risk

Alcohol can cause damage to DNA in blood stem cells

Adrian O'Dowd

Thursday, 04 January 2018

Experts say they have shown how alcohol damages DNA in stem cells thus helping to explain why drinking increases a person’s risk of cancer, according to new research* published in the journal Nature.

Alcohol is considered to cause seven types of cancer – mouth, upper throat, laryngeal, oesophageal, breast, liver and bowel.

Previous research looking at the precise ways in which alcohol causes cancer has been carried out in cell cultures, but for the new study, part-funded by Cancer Research UK, researchers used mice to show how alcohol exposure leads to permanent genetic damage.

Scientists at the MRC Laboratory of Molecular Biology, Cambridge, gave diluted alcohol (ethanol) to mice and then used chromosome analysis and DNA sequencing to examine the genetic damage caused by acetaldehyde – the harmful chemical produced when the body processes alcohol.

They found that acetaldehyde could break and damage DNA within blood stem cells leading to rearranged chromosomes and permanently altering the DNA sequences within these cells.

The researchers said it was important to understand how the DNA blueprint within stem cells was damaged because when healthy stem cells became faulty, they could lead to cancer.

The study also examined how the body tries to protect itself against damage caused by alcohol focusing on the first line of defence of the family of enzymes called aldehyde dehydrogenases (ALDH), which break down harmful acetaldehyde into acetate, which a person’s cells can use as a source of energy.

Worldwide, millions of people either lack these enzymes or carry faulty versions of them.

In the study, when mice lacking the critical ALDH enzyme (ALDH2) were given alcohol, it resulted in four times as much DNA damage in their cells compared to mice with the fully functioning ALDH2 enzyme.

Professor Ketan Patel, lead author of the study from the MRC Laboratory of Molecular Biology, said: “Some cancers develop due to DNA damage in stem cells. While some damage occurs by chance, our findings suggest that drinking alcohol can increase the risk of this damage.

“Our study highlights that not being able to process alcohol effectively can lead to an even higher risk of alcohol-related DNA damage and therefore certain cancers.

“But it’s important to remember that alcohol clearance and DNA repair systems are not perfect and alcohol can still cause cancer in different ways, even in people whose defence mechanisms are intact.”

This research was funded by Cancer Research UK, Wellcome and the Medical Research Council (MRC).

Professor Linda Bauld, Cancer Research UK’s expert on cancer prevention, said: “This thought-provoking research highlights the damage alcohol can do to our cells, costing some people more than just a hangover.”

* Garaycoechea JI, Crossan GP, Langevin F, et al. Alcohol-derived and endogenous aldehydes damage chromosomes and mutate stem cells. Nature, published online: 03 January 2018. DOI 10.1038/nature25154.

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