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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.

Which cancers?

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?

Ketan_Jayakrishna_Patel_FRS

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.

  • DNA clumps

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.

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.

Aine

Comments

Helena Conbear February 12, 2016

This is a very interesting article and attempts to break down the complex subject of alcohol and cancer well. If it is going to be truly balanced however, you should talk about dose and mention that drinking within the government guidelines does not increase your risk of most cancers. We communicate with thousands of parents in particular each year – and a true and balanced picture of alcohols risks and benefits is so important. even the case on breast cancer is unclear as risk seems to be negated if folate intake is adequate for example, risk is increased if BMI is high, it depends on the type of breast cancer too. Having looked at the evidence in great detail with our medical experts we are very happy communicating the low risk guidelines ( new as well as old) and feel scaring people who drink moderately is not helpful. We aim all our efforts at encouraging those who drink excessively to drink less – otherwise we risk alienating many and scaring ‘ the worried well’ without doing anything to reach those in most need of advice and support. There is no doubt that drinking above 30g of alcohol a day is strongly linked with the 7 types of cancer as well as many other illnesses and diseases, there is also a linear association with some types of breast cancer – but please make clear how many other types of cancers there are, and that if people lead moderate lives and drink within the guidelines, they are unlilkely to reduce their risk of cancer by drinking less. Teetotallers have worse outcomes in terms of all cause mortality than those who drink 10 – 20g a day.

Joan Brocklebank February 11, 2016

Thank you so much for that very informative ,article -would that this knowledge were more widely understood and acted on.

Lesley February 11, 2016

My mum died from oesophageal/abdominal cancer at 65 and my sister has had breast cancer at 50. The point that even small amounts can be a factor in oesophageal cancer has made me want to stop drinking (2-3 units not every week) at all due to genetic susceptibility- thanks for the wake up call.

stan February 11, 2016

Very technical but gives a dusting of every thing in moderation or else

Eric Watts February 10, 2016

I found this useful, sadly as it means I shall be drinking less, but on second thoughts I expect I’ll get used to it!
I’m more likely to cut down now that I’ve read some credible science.

Aine McCarthy February 10, 2016

Hi Nick,
Scientists have studied whether drinking alcohol increases a person’s risk of developing bladder cancer. Most of the research has shown that drinking alcohol does not have an effect on bladder cancer. But it’s important to remember alcohol does increase the risk of several other cancers.
Áine, Cancer Research UK

Aine McCarthy February 10, 2016

Hi Barbara,
Thanks for your comment. Cancer rates are increasing because people are living longer – we’ve written this blog post to explain the increase. There’s information about the link between air pollution and cancer in this blog post. And we also have this blog post discussing diesel emissions and public health.
Áine, Cancer Research UK

Mr Rabia Belatoui February 10, 2016

Great article, thank you.

trevor lewis February 10, 2016

I did not realize that even small amounts of drink can be harmfull ;so these bulletins are
really important; ive had cancer twice now ;and that word still has a massive effect on the person involved ; keep it up good work. thanks.

Julian Wyer February 10, 2016

One aspect to bear in mind when looking at alcoholic products is that most of these have undergone a production process involving fermentation and this also produces varying levels of a class of compound know as urethanes (ethyl carbamate derivatives). Urethanes are known human carcinogens. They are at higher levels in types of drinks like traditional ales. However, not to frighten everyone but urethanes are also present to certain levels in other foods that undergo partial fermentation, like bread, soy sauce, pickles and the like!

Nick Chandler February 10, 2016

A very interesting article. I notice that cancer of the bladder is not mentioned as being related to alcohol consumption or level of exposure. Is there an explanation for this ?

Caroline Bibby February 9, 2016

I didnt drink more than a couple of units a week and that was rarely. I exercised daily, could run marathons but still was diagnosed with breast cancer at 45 years old. Never smoked a cigarette in my life. So sorry do not believe enough research has been done yet.

Karen Saxl February 9, 2016

Very interesting – good to see folate problems mentioned but has any thought been given to B12 interactions? either through the effect of alcohol on the liver and hence on ability to store and recycle B12, or the prevalence of undiagnosed B12 absorption problems.

John Elwood February 9, 2016

Interesting and informative.
This knowledge has prompted me to pass on this information to the members of my family who drink alcohol.

Jackie Cheshire February 9, 2016

Being a Heathcate Assistant for a GP surgery, I find myself advising patients about the association between Alcohol and some Cancers. I think that by using the information here it will help my patients to make a more informed decision about their Alcohol consumption. And hopefully they will pass the information on to others.

Edwina Saunderd February 9, 2016

Excellent paper. Frightened me. Will try harder.

Julian Wyer February 9, 2016

Does each successive generation have a weaker autoimmune system thereby letting cancers through more easily? If this is the case, then factors such as alcohol (and its toxic degradation products) might/will have a greater influence compared to past generations.

What have the current and last generation been exposed to in early years and teens that earlier generations have not? Chemicals, electromagnetic radiations (increase in natural and man-made, cosmic radiation from high altitude flights), specific viruses.

Without doubt, the initiation of any cancer is a complex process and the effect of any single trigger (such as alcohol intake) has to be investigated in combination with all the above additional factors.

Linda Penney February 9, 2016

Increasingly, it seems clear that individuals have varying genetic susceptibility to cancer, often presenting through family histories; you may inherit genes which are more likely to mutate, some mutations initiating tumour growth. Certain environmental triggers will increase the chances of mutation. These are known to include smoking, radiation, diet, lifestyle and certain chemicals, such as alcohol. Limiting exposure to these will reduce the risk of developing cancer but, for an individual, one has to consider the overall picture. Giving up alcohol, while ignoring other lifestyle risk factors, will have a small impact.

N Field February 9, 2016

I would request that Cancer Research UK think very carefully about the way they put across these messages about the causes of cancer. A friend of mine died last April of Breast Cancer at the age of 48 and she left 3 fairly young children. For three years between being diagnosed and dying she said that sometimes she felt like she needed to hang her head in shame as the suggestion with headlines was that basically because she enjoyed a glass of wine that she had subjected her children to a life without a mother. When in fact the truth of the matter, or so it seems, is that if you drink alcohol there is a possibility that your genetic make up means that you are more predisposed than others to getting it. It does not mean that because you have breast cancer that you have drunk more than everyone else, it is bad enough when you get cancer let alone then having to spend all of your energy defending yourself. I completely agree that warnings need to be given but lets be clearer about the message to prevent those in the unfortunate position of suffering being made to feel guilty. Nobody blames anyone for having a cold!

M. Dainton February 9, 2016

This is interesting and informative but like a note below I do wonder about the chemicals we inhale everyday from car exhausts and the additives or chemicals in food that we don’t know about that are ‘allowed’…… The mix of all these things should be questioned.

Barbara Betts February 9, 2016

Very informative and interesting but as to the ? Why cancer rates are increasing… How about the damage done by car exhaust pollution we all inhale everyday of the week and can’t avoid???

Julian Wyer February 9, 2016

Acetaldehyde (from ethanol) is indeed a very reactive and toxic substance. The process of carcinogenesis is far more complex than just the effect of acetaldehyde alone. Other substances in our food chain (whether they be additives such as nitrates, residues from pesticides or naturally occurring substances) may cause a complex chemical reaction with chemicals like acetaldehyde producing nitroso compounds and similar, known to be carcinogens. Alcohol may be a trigger but far more research is needed to determine why the rate of cancer is increasing at such at an alarming rate.

R. Steed February 9, 2016

Very good i was very surprised to read some of this.

Mark Rose February 9, 2016

One minute they tell us malt whiskey and red wine might actually help in preventing cancer, but now they tell us even light drinking causes it.. My grandad drank a glass of whiskey or brandy every night and he lived to be 87 (died of skin cancer which isn’t even related).

Leslie Slade February 9, 2016

Very informative, thank you.