A team of researchers from the Wellcome Trust Sanger Institute, the MRC Laboratory of Molecular Biology and the University of Cambridge, UK, has shown how alcohol damages chromosomes and mutates stem cells, helping to explain why drinking alcohol increases the risk of developing seven types of cancer.
There are many ways alcohol may cause cancer including directly damaging DNA, increasing levels of certain hormones and damaging the liver. Image credit: Laura M.
“This thought-provoking research highlights the damage alcohol can do to our cells, costing some people more than just a hangover,” said Cancer Research UK’s expert Professor Linda Bauld, who was not involved in the study.
“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.”
Much previous research looking at the precise ways in which alcohol causes cancer has been done in cell cultures.
But in this new study, the scientists have used mice to show how alcohol exposure leads to permanent genetic damage.
They gave ethanol to mice and used chromosome analysis and DNA sequencing to examine the genetic damage caused by acetaldehyde, a harmful chemical produced when the body processes alcohol.
They found that acetaldehyde can break and damage DNA within blood stem cells leading to rearranged chromosomes and permanently altering the DNA sequences within these cells.
It is important to understand how the DNA blueprint within stem cells is damaged because when healthy stem cells become faulty, they can give rise to cancer.
“Some cancers develop due to DNA damage in stem cells,” said study senior author Professor Ketan Patel, from the MRC Laboratory of Molecular Biology.
“While some damage occurs by chance, our findings suggest that drinking alcohol can increase the risk of this damage.”
The researchers also examined how the body tries to protect itself against damage caused by alcohol.
The first line of defense is a family of enzymes called aldehyde dehydrogenases (ALDH).
These enzymes break down harmful acetaldehyde into acetate, which our cells can use as a source of energy. Millions of people 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, when mice lacking the critical ALDH enzyme, called 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.
The second line of defense used by cells is a variety of DNA repair systems which, most of the time, allow them to fix and reverse different types of DNA damage.
But they don’t always work and some people carry mutations which mean their cells aren’t able to carry out these repairs effectively.
““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,” Professor Patel said.
“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 defense mechanisms are intact.”
The results were published online January 3, 2018 in the journal Nature.
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Juan I. Garaycoechea et al. Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells. Nature, published online January 3, 2018; doi: 10.1038/nature25154
