In a cabinet in London’s British Museum nestles a 5,300 year-old wedged-shaped tablet called a cuneiform. On its surface is scrawled one of the earliest forms of written language in the world.
And it’s a record of Mesopotamian workers’ beer rations.
Clearly, humanity’s relationship with alcohol stretches back thousands of years, but a long relationship doesn’t necessarily mean a healthy one.
We know that alcohol is damaging to our health in a number of ways. And the one we’re most concerned about here at Cancer Research UK is its impact on cancer risk.
We’ve written about the link between alcohol and cancer many times before – from discussing the evidence that it causes cancer to talking about how drinking less reduces your risk of developing the disease.
But we haven’t yet explored the science behind how alcohol affects and damages our cells, and how this can cause the cells in our bodies to develop into cancer.
There are seven types of cancer linked to alcohol – bowel, oesophageal (food pipe), larynx (voice box), mouth, pharynx (upper throat), breast (in women), and liver. There’s also mounting evidence that heavy drinking might be linked to pancreatic cancer. But how, and why?
According to Dr Ketan Patel, a Cancer Research UK expert on how alcohol causes cancer: “We don’t really know. We don’t fully understand why alcohol causes some cancers and not others.”
There are some theories, however, although some are stronger than others.
The best evidence we have is for mouth and throat cancers where alcoholic drinks directly damage cells in these tissues.
And, because alcohol also increases a person’s chances of developing a scarring of the liver known as cirrhosis, it’s thought that this increases their chances of developing liver cancer.
There’s also some evidence that certain bacteria in your mouth and throat – and maybe even in the bowel – could be involved in alcohol causing cancer. But the link isn’t clear and we don’t know for sure, so we need to wait for more data.
And, as we will briefly discuss below, there’s good reason to think that alcohol’s effects on hormone levels might be behind its link to breast cancer.
While there may be a perception that the health risks of alcohol only apply to heavy drinkers, research is revealing that it’s not just drinking large amounts of alcohol that increases your chances of developing cancer – drinking small amounts can be harmful too.
Although there’s a lot we still don’t know about how alcohol is linked to different types of cancer, researchers are starting to figure out at least one of the ways that it causes harm.
A nervous breakdown
Like most things you eat or drink, alcohol – be it in a pint, shot or cocktail – gets broken down by your cells.
In the case of ethanol – the chemical name for the alcohol we drink – it ultimately gets broken down to create energy.
First an enzyme called alcohol dehydrogenase (ADH) converts ethanol to another molecule – acetaldehyde. This then gets broken down by a second enzyme, acetaldehyde dehydrogenase (ALDH), into acetate, which our cells can use as a source of energy.
This is a relatively straightforward process, and one that evolution has equipped our bodies to handle with ease. So where’s the harm in having a drink or two?
Dr Ketan Patel Image via Wikimedia Commons CC-BY-3.0
The risk lies with the middle man – acetaldehyde.
“Ethanol itself is relatively non-toxic other than the consequences of drunkenness,” says Ketan Patel. “It doesn’t directly damage DNA. But as the body breaks it down, it goes through a step where it is converted to a highly reactive, toxic chemical called acetaldehyde.”
“And it’s a build-up of this which likely causes changes that lead to cancer.”
To prevent acetaldehyde building up and damaging DNA, human cells contain three ALDH enzymes – ALDH1A1, ALDH2 and ALDH1B1, which rapidly break down acetaldehyde into acetate. This means that acetaldehyde doesn’t usually have time to build up or hang around for long enough to cause significant DNA damage.
But this protection mechanism can be overwhelmed once alcohol is in the bloodstream, meaning it doesn’t work properly.
What’s more, it isn’t available to everyone. Some people have mistakes or changes in the genetic code of their ALDH enzymes which cause them to malfunction, so acetaldehyde can build up. In turn, this leads to DNA damage.
“It’s known as the flushing mutation” says Patel. “It’s particularly common among Southeast Asian populations – for example, up to 70% of the Taiwanese population have it.”
“People with mutated ALDH enzymes become flushed in the face and very often feel very sick after drinking alcohol.”
Thankfully, our cells contain a further layer of protection, in the form of a variety of ‘toolkits’ that can repair damaged DNA (which we’ve discussed at length in this post).
But both of these systems have their limits, so damage can still happen.
“Most organisms – from bacteria to humans – have these two protection systems. But if you overwhelm them they won’t work,” says Patel. “That’s when you get acetaldehyde causing DNA damage and changes that lead to cancer.”
Mutations and rearrangements and clumps….
This is an important part of the chain of evidence linking alcohol to cancer risk.
“The evidence that mistakes in DNA can lead to cancer is overwhelming,” says Patel.
So how exactly does acetaldehyde affect our cells’ DNA? Over the years, scientists have identified several forms of damage.
DNA ‘spelling mistakes’
Acetaldehyde can cause errors in DNA called point mutations. These are a type of mistake where one base – or ‘letter’ – in a gene is swapped for another. And because DNA is the instruction manual that tells our cells what to do, mistakes in it can lead to cancer.
Rearranging the furniture
Acetaldehyde can also trigger larger-scale changes to our DNA, by messing up entire chromosomes (the technical name for the long strings of DNA in our cells). It can cause bits of chromosomes to break off and to swap around, meaning genes end up in the wrong place and don’t work properly – these are also phenomena that can trigger cancer.
Acetaldehyde has also been shown to bind to DNA, forming clumps called adducts. These play havoc with how DNA works, folds, replicates and repairs itself. Essentially, adducts are another type of mutation, and they too can cause cells to become cancerous.
The cup runneth over
So far we’ve seen that alcohol can be broken down into a harmful chemical – acetaldehyde. We’ve looked at the systems in place to prevent it damaging our DNA. And we’ve looked at the sorts of damage it can cause.
Now let’s take a closer look at what’s going on when we have a drink or two. To visualise how alcohol overwhelms our cellular defences, imagine you’re pouring alcohol – say red wine – into a glass through a funnel.
If you only pour a small amount into the funnel, the wine will flow right through.
But if you continuously pour the alcohol into the funnel, without taking time to stop or pause, the funnel will overflow.
Similarly, too much alcohol stops the ALDH enzymes and DNA repair pathways from working properly, so the systems become overwhelmed, resulting in a build-up of acetaldehyde, and damage that can lead to cancer.
While this neatly explains why certain cancers – such as bowel and liver tumours – are linked to heavy drinking, what’s more of a mystery is why other forms are linked to much lower levels of consumption.
For example, we know that light drinking increases a person’s risk of developing cancers of the upper aero-digestive tract, namely mouth, upper throat and oesophageal cancers.
One theory that might explain this is the bacteria we mentioned earlier. It’s thought that the bacteria in our mouth are very good at converting ethanol into acetaldehyde, resulting in a very high level of acetaldehyde, even if only a small bit of booze is drunk.
Clearly there’s a lot more work to be done to really understand how the ‘funnel’ idea plays out in different tissues of our bodies, and just how much (or little) alcohol can cause it to ‘overflow’. As well as why some forms of cancer are more strongly linked to alcohol than others.
But as well as acetaldehyde causing DNA damage, there are other ways alcohol can lead to cancer too.
Other potential mechanisms
Smoking is the number one preventable cause of cancer. So it’s not surprising that if someone drinks and smokes, they’re increasing their chances of developing cancer even further. But for some cancers, it seems that these two effects in combination are much worse than either by itself. Why?
The interaction between alcohol and smoking is complex. Acetaldehyde is also a by-product of burning tobacco, as is a second, similar chemical: formaldehyde.
But to go back to our funnel, if you drink and smoke there’s more chance of creating an overflow because the body’s systems can’t work fast enough to handle the damage caused by both of them at the same time.
“If you smoke and drink, you’re going to have a greater build-up of acetaldehyde and other toxins, which will increase the damage to your DNA and, in turn, your chances of developing cancer.”
As well as this, there’s also evidence that alcohol can make it easier for the cancer-causing tobacco chemicals found in cigarettes to get into tissue and cells.
Alcohol increases a woman’s chances of developing breast cancer – but how and why this happens still isn’t fully understood.
One theory is that drinking alcohol affects women’s hormone levels, increasing the amount of oestrogen in the body, which is then used by breast cancer cells as fuel for growth.
But it’s not necessarily straightforward to unravel. Lots of other things affect oestrogen levels, including whether the woman is pre- or post-menopausal, the stage of her menstrual cycle and whether she’s taking hormonal contraceptives or hormone replacement therapy (HRT).
Patel is cautious. “We know alcohol increases women’s risk of developing breast cancer. But so far, the exact mechanism that causes this increased risk hasn’t been pinned down,” he says. “At the moment, the evidence is too weak to say for definite how alcohol causes breast cancer.”
“We need more research to figure out this complex cause-and-effect relationship.”
More or less?
Research is slowly revealing more about how alcohol causes cancer, and the theories we’ve discussed in this post are the ones with the strongest supporting evidence.
But there are other ideas that haven’t yet been fully explored or resolved. These include changes in folate metabolism, increased production of reactive oxygen species and reactive nitrogen species and the role of bacteria in how alcohol is metabolised.
At Cancer Research UK, we’re committed to finding out more about the mechanisms by which alcohol causes cancer.
Health news in pictures
Health news in pictures
1/22 New online test predicts skin cancer risk
Health experts have created a new online tool which can predict a person’s risk of developing a common form of skin cancer. The tool uses the results of a 10-question-quiz to estimate the chance of a person aged 40 or over of having non-melanoma skin cancers within three years. Factors including the age, gender, smoking status, skin colour, tanning ability, freckling tendency, and other aspects of medical history are covered by the quiz
2/22 Multiple Sclerosis stem cell treatment 'helps patients walk again'
A new treatment for multiple sclerosis (MS) has enabled some patients to walk again by “rebooting” their immune systems. As part of a clinical trial at Sheffield's Royal Hallamshire Hospital involving around 20 patients, scientists used stem cells to carry out a bone marrow transplant. The method known as an autologous haematopoietic stem cell transplant (HSCT) works by using chemotherapy to destroy the area of the immune system which causes MS
3/22 Dementia patients left without painkillers and handcuffed to bed
Dementia patients experience a ‘shocking’ variation in the quality of hospital care they receive across England, a charity has warned. Staff using excessive force and not giving dementia patients the correct pain medication were among the findings outlined in a new report by The Alzheimer’s Society, to coincide with the launch of Fix Dementia Care campaign
4/22 Cancer risk 'increased' by drinking more than one glass of wine or pint of beer per day
Drinking more than one glass of wine or pint of beer a day increases the risk of developing cancer, according to medical experts. New guidelines for alcohol consumption by the UK published by chief medical officers warn that drinking any level of alcohol has been linked to a range of different cancers. The evidence from the Committee on Carcinogenicity (COC) overturns the oft-held view that a glass of red wine can have significant medical benefits for both men and women
5/22 Vaping 'no better' than smoking regular cigarettes
Vaping could be “no better” than smoking regular cigarettes and may be linked to cancer, scientists have found. The study which showed that vapour from e-cigarettes can damage or kill human cells was publsihed as the devices are to be rolled out by UK public health officials as an aid to quit smoking from 2016. An estimated 2.6 million people in the UK currently use e-cigarettes
6/22 Rat-bite fever
A teenager was hospitalised and left unable to move after she developed the rare rat-bite fever disease from her pet rodents which lived in her bedroom. The teenager, who has not been named, was taken to hospital after she complained of a pain in her right hip and lower back which later made her immobile, according to the online medical journal BMJ Case Reports. She suffered for two weeks with an intermittent fever, nausea and vomiting and had a pink rash on her hands and feet. The teenager, who had numerous pets including a dog, cat, horse and three pet rats, has since made a full recovery after undergoing a course of antibiotics. Blood tests showed that she was infected with for streptobacillus moniliformis – the most common cause of rat-bite fever. One of her three pet rats lay dead in her room for three weeks before her symptoms showed
7/22 Taking antidepressants in pregnancy ‘could double the risk of autism in toddlers’
Taking antidepressants during pregnancy could almost double the risk of a child being diagnosed with autism in the first years of life, a major study of nearly 150,000 pregnancies has suggested. Researchers have found a link between women in the later stages of pregnancy who were prescribed one of the most common types of antidepressant drugs, and autism diagnosed in children under seven years of age
8/22 Warning over Calpol
Parents have been warned that giving children paracetamol-based medicines such as Calpol and Disprol too often could lead to serious health issues later in life. Leading paediatrician and professor of general paediatrics at University College London, Alastair Sutcliffe, said parents were overusing paracetamol to treat mild fevers. As a result, the risk of developing asthma, as well as kidney, heart and liver damage is heightened
9/22 Fat loss from pancreas 'can reverse' effects of type-2 diabetes
Less than half a teaspoon of fat is all that it takes to turn someone into a type-2 diabetic according to a study that could overturn conventional wisdom on a disease affecting nearly 3 million people in Britain. Researchers have found it is not so much the overall body fat that is important in determining the onset of type-2 diabetes but the small amount of fat deposited in the pancreas, the endocrine organ responsible for insulin production
10/22 Potatoes reduce risk of stomach cancer
Scientists have found people who eat large amounts of white vegetables were a third less likely to contract stomach cancer. The study, undertaken by Chinese scientists at Zhejiang University, found eating cauliflower, potatoes and onions reduces the chance of contracting stomach cancer but that beer, spirits, salt and preserved foods increased a person’s risk of the cancer
11/22 Connections between brain cells destroyed in early stages of Alzheimer’s disease
Scientists have pinpointed how connections in the brain are destroyed in the early stages of Alzheimer’s disease, in a study which it is hoped will help in the development of treatments for the debilitating condition. At the early stages of the development of Alzheimer’s disease the synapses – which connect the neurons in the brain – are destroyed, according to researchers at the University of New South Wales, Australia. The synapses are vital for brain function, particularly learning and forming memories
12/22 Sugar tax
The Government should introduce a sugar tax to prevent an “obesity crisis” from crippling the NHS, a senior Conservative MP and former health minister has said. Dr Dan Poulter believes that the case for increased taxes on unhealthy sugary products was “increasingly compelling”
13/22 Cancer breakthrough offers new hope for survivors rendered infertile by chemotherapy
A potentially “phenomenal” scientific breakthrough has offered fresh hope to cancer patients rendered infertile by chemotherapy. For the first time, researchers managed to restore ovaries in mice affected by chemotherapy so that they were able to have offspring. The scientists now plan to begin clinical trials to see if the technique, which involves the use of stem cells, will also work in humans by using umbilical cord material and possibly stem cells taken from human embryos, if regulators agree
14/22 Take this NHS test to find out if you have a cancerous mole
An interactive test could help flag up whether you should seek advice from a health professional for one of the most common types of cancer. The test is available on the NHS Choices website and reveals whether you are at risk from the disease and recommends if you should seek help. The mole self-assessment factors in elements such as complexion, the number of times you have been severely sunburnt and whether skin cancer runs in your family. It also quizzes you on the number of moles you have and whether there have been any changes in appearance regarding size, shape and colour
15/22 Health apps approved by NHS 'may put users at risk of identity theft'
Experts have warned that some apps do not adequately protect personal information
16/22 A watchdog has said that care visits must last longer
The National Institute for Health and Care Excellence (Nice) said home help visits of less than 30 minutes were not acceptable unless part of a wider package of support
17/22 Pendle in Lancashire tops list of five most anxious places to live in the UK
Pendle in Lancashire has been named the most anxious place to live in the UK, while people living in Fermanagh and Omagh in Northern Ireland have been found to be the happiest
18/22 Ketamine could be used as anti-depressant
Researchers at the University of Auckland said monitoring the effects of the drug on the brain has revealed neural pathways that could aid the development of fast-acting medications. Ketamine is a synthetic compound used as an off anaesthetic and analgesic drug, but is commonly used illegally as a hallucinogenic party drug. Dr Suresh Muthukumaraswamy, a senior researcher at the university and a member of the institution’s Centre for Brain Research, used the latest technology in brain imaging to investigate what mechanisms ketamine uses to be active in the human brain
19/22 A prosthetic hand that lets people actually feel through
The technology lets paralysed people feel actual sensations when touching objects — including light taps on the mechanical finger — and could be a huge breakthrough for prosthetics, according to its makers. The tool was used to let a 28-year-old man who has been paralysed for more than a decade. While prosthetics have previously been able to be controlled directly from the brain, it is the first time that signals have been successfully sent the other way
20/22 The biggest cause of early death in the world is what you eat
Unhealthy eating has been named as the most common cause of premature death around the globe, new data has revealed. A poor diet – which involves eating too few vegetables, fruits, nuts and grains and too much red meat, salt and sugar - was shown to be a bigger killer than smoking and alcohol
21/22 Scientists develop blood test that estimates how quickly people age
Scientists believe it could be used to predict a person’s risk of developing Alzheimer’s disease as well as the “youthfulness” of donated organs for transplant operations. The test measures the vitality of certain genes which the researchers believe is an accurate indication of a person’s “biological age”, which may be younger or older than their actual chronological age
22/22 Aspirin could help boost therapies that fight cancer
The latest therapies that fight cancer could work better when combined with aspirin, research has suggested. Scientists from the Francis Crick Institute in London say the anti-inflammatory pain killer suppresses a cancer molecule that allows tumours to evade the body’s immune defences. Laboratory tests have shown that skin, breast and bowel cancer cells often generate large amounts of this molecule, called prostaglandin E2 (PGE2). But Aspirin is one of a family of drugs that sends messages to the brain to block production of PGE2 and this means cancer cells can be attacked by the body’s natural defences
We’re continuing to fund Dr Patel’s research, which is focusing on how alcohol is broken down into different chemicals in the body and how this can damage cells and trigger cancers – particularly liver cancer. He is also studying both the long and short-term effects of exposure to alcohol.
And one of the big questions raised by our Grand Challenge funding scheme is asking if the mutational fingerprints left behind by lifestyle factors like drinking alcohol can help us better understand the link between environmental factors and cancer.
But no matter how alcohol causes cancer, one thing is clear.
The best way to reduce the risk of cancer from alcohol is to drink less of it – whether that’s by having more alcohol-free days every week, swapping out some glasses of booze for soft drinks during a night out, or picking lower strength drinks or smaller servings.
The relationship between humans and alcohol goes back millennia and it’s an integral part of many societies’ social lives. Of course, adults have the right to decide how much they want to drink, but alcohol’s health impacts are undeniable. By working with the Government, policy-makers and healthcare professionals, we’re aiming to raise awareness of the risks of alcohol and help people make choices that can reduce their cancer risk.