Cambridge scientists discover why drinking alcohol increases your risk of cancer
Researchers at MRC Laboratory of Molecular Biology show it causes permanent DNA damage
Cambridge scientists have helped to explain why drinking alcohol increases your risk of cancer.
The researchers at the MRC Laboratory of Molecular Biology showed that alcohol damages stem cells, causing permanent damage to DNA - splitting it in two.
Every year, alcohol is believed to cause about 12,800 cases of cancer in the UK - about 4 per cent of the total. It is certainly motivation to keep going for those who have banished the bottle for ‘Dry January’.
Much previous research on the links between alcohol and cancer has focused on cell cultures.
But in this study, published in the journal Nature, the scientists gave diluted alcohol – ethanol – to mice.
Using chromosome analysis and DNA sequencing, they demonstrated the genetic damage caused by acetaldehyde, a harmful chemical that is produced when the body processes alcohol.
Acetaldehyde can break and damage DNA within blood stem cells, they found. This leads to rearranged chromosomes and permanently alters DNA sequences within these cells.
This is significant because when healthy stem cells become faulty, it can lead to cancer. There has been speculation in recent years that it is the rate at which stem cells divide and create new cells that increases the risk of cancers in different parts of the body.
Lead author Professor Ketan Patel, whose role is part-funded by Cancer Research UK at the MRC LMB on Cambridge Biomedical Campus, 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.”
Although alcohol is not thought to cause blood cancer, using blood stem cells was a useful way for scientists to investigate what’s happening to the DNA inside.
Prof Patel explained: “They’re a good way of monitoring changes and damage to DNA in a way that’s more informative than looking at cells in a dish.”
It is known that drinking alcohol increases the risk of seven types of cancer – mouth, upper throat, laryngeal, oesophageal, breast, liver and bowel.
The researchers explored how the body’s two-tier system for protecting itself against the damage it causes, with the first line of defence being a family of enzymes called aldehyde 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,” said Prof Patel.
However, millions of people across the world – particularly those from South East Asia – lack these enzymes or carry faulty versions of them.
This means when they drink alcohol, acetaldehyde builds up, causing a flushed complexion and causing them to feel unwell.
The researchers genetically engineered mice which had blood stem cells that did not produce a critical enzyme called ALDH2, meaning they could not break down acetaldehyde.
After giving the mice diluted ethanol, they read their DNA code and were struck by the results.
In bone marrow samples carrying blood cells lacking the enzyme, a single 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,” said Prof Patel.
The mice lacking ALDH2 had four times as much DNA damage in their cells compared to the mice with a fully-functioning ALDH2 enzyme.
Examining carefully-extracted stem cells from the mice, they found the DNA had been broken in two by acetaldehyde – a pattern of DNA damage that has the potential to turn cells cancerous.
“Our work definitively shows that external factors, like drinking alcohol, can damage DNA in blood stem cells, meaning it could also damage DNA in other types of stem cells,” said Prof Patel.
“While we didn’t look at whether these mice got cancer or not, previous studies have shown that the type of DNA damage we saw in these mice can considerably increase the risk of cancer.”
The body’s second line of defence against alcohol damage is a variety of DNA repair systems. These mechanisms normally fix and reverse types of DNA damage but are not always successful. Some people carry mutations that means their cells are not able to carry out the repairs effectively.
“There are lots of ways cells can fix DNA damage,” said Prof 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 primary way the body repairs acetaldehyde-related damage is through the Fanconi anaemia repair pathway.
For those who have faults in molecules that carry out these repairs, there are two other repair options for blood stem cells to use - the non-homologous end-joining repair pathway and the homologous recombination pathway.
“The first line of defence is the ALDH enzymes. But if these are faulty or missing, stem cells use different repair pathways in a co-ordinated way to fix any damage caused by acetaldehyde and prevent it being passed on to the cells they produce,” said Prof Patel.
He 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.”
The work 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.
“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.
No ‘safe’ alcohol limit
Cancer Research UK advises that the less alcohol you drink, the lower the risk of cancer.
It is the alcohol itself that leads to the damage, regardless of whether it is in wine, beer or spirits. Drinking and smoking together are worse still because tobacco and alcohol work together to damage the cells of the body. Alcohol, for example, makes it easier for the mouth and throat to absorb the carcinogenic chemicals in tobacco.
While there is no ‘safe’ limit of alcohol to consume, the cancer risk is smaller for those who drink within government guidelines. Currently, it is advised that you should not drink more than 14 units a week on a regular basis – equivalent to six pints of average strength beer or six 175ml glasses of average strength wine.
By raising the level of hormones such as oestrogen in the body, alcohol can cause breast cancer.
About 3,200 cases of breast cancer each year in the UK are linked to alcohol.
It has a weaker effect on the risk of breast cancer than on cancers of the head and neck.
However, breast cancer is the most common cancer in the UK and as many women drink small amounts of alcohol regularly the number affected is high.
Drinking alcohol can also damage liver cells, leading to cirrhosis, which makes you more likely to develop liver cancer.
Alcohol can cause cells to produce highly reactive molecules, called Reactive Oxygen Species (ROS), which can damage DNA.
Drinking alcohol caused an estimated 6% of deaths worldwide in 2012, 13% of which were due to cancer.
Alcohol caused an estimated 5% of deaths in England in 2010, around half of which were due to cancer.
Reducing average alcohol intake in England by around one unit per person per day would avoid an estimated 8% of cancer deaths.
Drinking alcohol causes an estimated 4% of cancer cases in the UK each year - about 12,800 cases.
Tips for cutting down on alcohol from Cancer Research UK
Whether you use smaller glasses, or pick for weaker or alcohol-free alternatives to your usual tipple, there are many ways to cut down alcohol. Here are some tips from Cancer Research UK:
• Have more alcohol-free days a week. Try agreeing on certain days with your partner or a friend and help each other to stick to it.
• If you are planning to drink alcohol, decide on a limit in advance and make sure you don’t go over it.
• Swap every other alcoholic drink for a soft one – starting with your first drink.
• Try shandy instead of a pint of beer, or swap some wine for soda and have a spritzer.
• Don’t stock up on beer, wine or spirits at home.
• Finish one drink before pouring another, because topping up drinks makes it harder to keep track of how much you’ve had and when you planned to stop.
• Avoid buying drinks in rounds, that way you don’t have to keep pace with anyone.
• Tell a friend or partner that you’re cutting down on alcohol, they can support you – or even join you.
More by this authorPaul Brackley