Alcohol Can Cause Irreversible Genetic Damage.
Alcohol can cause irreversible genetic damage to the body’s reserve of stem cells, according to a study that helps explain the link between drinking and cancer. The research, using genetically modified mice, provides the most compelling evidence to date that alcohol causes cancer by scrambling the DNA in cells, eventually leading to deadly mutations. During the past decade, there has been mounting evidence of the link between drinking and the risk of certain cancers. “How exactly alcohol causes damage to us is controversial,” said Prof Ketan Patel, who led the work at the MRC Laboratory of Molecular Biology in Cambridge. “This paper provides very strong evidence that an alcohol metabolite causes DNA damage [including] to the all-important stem cells that go on to make tissues.”
The study builds on previous work that had pinpointed a breakdown product of alcohol, called acetaldehyde, as a toxin that can damage the DNA within cells. However, these earlier studies had relied on extremely high concentrations of acetaldehyde and used cells in a dish rather than tracking its effects within the body. The latest work showed that acetaldehyde slices through DNA, causing permanent damage if the effects of the toxin are not neutralised by two natural defence mechanisms. The first tier of defence clears away the acetaldehyde and the second repairs the DNA damage. By genetically “knocking out” these two layers of defence, scientists were able to show DNA damage accumulating until cells eventually stopped working entirely.
The study revealed that DNA damage was exacerbated when mice lacked the first tier of defence – a protective enzyme called aldehyde dehydrogenase 2 (ALDH2), which prevents potentially toxic build-ups of acetaldehyde. About 8% of the world’s population, mostly those of East Asian ancestry, have an inherited deficiency in ALDH2 (sometimes known as the flushing mutation), which could explain the high prevalence of oesophageal cancers in countries such as China.
The study, published in the journal Nature, focused on stem cells within the blood, which the body relies on to continually supply fresh blood throughout life. Blood cells were singled out because they can be multiplied readily, allowing the DNA to be sequenced more easily, but the scientists believe that the effects of alcohol could be similar in other cell types. In mice that lacked both natural defences against alcohol, their ability to produce fresh blood was destroyed after being given diluted alcohol for ten days, the study found. Sequencing the genome of the stem cells showed that their DNA had been scrambled to the point that the cells no longer functioned. “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,” said Patel. “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.”
The team now plan to investigate why drinking is linked to certain cancers but not others. Alcohol consumption causes around 4% of cancers in the UK, or around 12,800 cases each year. 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. But there is no evidence that drinkers are at a substantially increased risk of blood cancers, say, experts, despite the new findings showing that drinking can alter the DNA in blood stem cells. “The blood system has a very stringent quality control mechanism to get rid of anything that is damaged,” said Patel, adding that this might explain why alcoholics tend to become severely anaemic. It is possible that the body’s defence mechanisms against acetaldehyde are weaker in other tissues.
Prof Magdalena Zernicka-Goetz, a stem cell biologist at the University of Cambridge, said the findings were very important: “This is beautiful work which puts our finger on the molecular basis for the link between alcohol and increased cancer risk and stem cells,” she said. Prof Linda Bauld, an expert on cancer prevention at Cancer Research UK, which partly funded the research, 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.”
Credit: Hannah Devlin for The Guardian, 3 January 2018.