The study was partly funded by Cancer Research UK. Professor Ketan Patel, lead author of the study and scientist at 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."

Scientists already know cells can protect their DNA from acetaldehyde by using a group of enzymes called acetaldehyde dehydrogenases (ALDH).

“When they’re working properly, the ALDH enzymes stop acetaldehyde building up by converting it into acetate, which cells can use as a source of energy,” says Patel.

To see the damage acetaldehyde might cause to stem cells’ DNA, Patel and his team had to look at cells that didn’t have these enzymes.

To do this, they used lab-based genetic engineering to create mice whose blood stem cells didn’t produce the enzyme ALDH2, meaning they couldn’t break down acetaldehyde.

They then gave these mice diluted ethanol, the purest form of alcohol, and used techniques to see the DNA inside the cells and read its code.

According to Patel, the results were striking and remarkable.

They found that in bone marrow samples carrying blood cells lacking the ALDH2 enzyme, just one dose of ethanol caused a build-up of acetaldehyde that seriously damaged the DNA.

“We saw huge amounts of DNA damage in these cells. Bits of DNA were deleted, bits were broken and we even saw parts of chromosomes being moved about and rearranged,” he says.

Worldwide, millions of people, particularly those from South East Asia, either lack these enzymes or carry faulty versions of them. So, when they drink, acetaldehyde builds up which causes a flushed complexion, and also leads to them feeling unwell.

In the study, mice that were lacking the critical ALDH enzyme -- ALDH2 --   had four times as much DNA damage in their cells compared to mice with the fully functioning ALDH2 enzyme after alcohol consumption.

“There are lots of ways cells can fix DNA damage,” says Patel. “What we’ve shown is that when damage happens as a result of breaking down alcohol, there’s a hierarchy when selecting the best way to carry out repairs.”

The team found the main way acetaldehyde-related damage is fixed is through the Fanconi anaemia repair pathway.

But some people have faults in the molecules that carry out these repairs, meaning their cells need to use others.

Professor Patel added: "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."

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.

"We know that alcohol contributes to over 12,000 cancer cases in the UK each year, so it's a good idea to think about cutting down on the amount you drink."

Story Source:

Materials provided by Cancer Research UK. Note: Content may be edited for style and length.

Journal Reference:

1. Juan I. Garaycoechea, Gerry P. Crossan, Frédéric Langevin, Lee Mulderrig, Sandra Louzada, Fentang Yang, Guillaume Guilbaud, Naomi Park, Sophie Roerink, Serena Nik-Zainal, Michael R. Stratton, Ketan J. Patel. Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells. Nature, 2018; DOI: 10.1038/nature25154