Wednesday, 8 December 2010

A daily aspirin pill cuts cancer risk by 21%

crabsallover highlights in bold and my comments in bold blue.

I've made 4 previous blogs on Aspirin & health on ScienceHealthyLongLife since 2008 & more posts since 2006 on my crabsallover blog. The last here was in October when Peter Roswell et al (who undertook this latest research) found reductions in Bowel Cancer with Aspirin. In February 2007 I concluded that risk of bleeding was too great when compared to the reduced risks of heart attack or stroke. However Peter Roswell et al results of Aspirin on effect of various cancers, reported below, now means that for the next 21 years & until I'm 75, I, like Fergus Walsh, will be taking 75mg aspirin per day.  

"Professor Rothwell said the annual risk of major internal bleeding was about 1 in 1,000 and aspirin roughly doubled that risk. But he said the danger of major bleeding was "very low" in middle age but increased dramatically after 75. A sensible time to consider starting daily aspirin use would be between 45-50, continuing for around 25 years, he said." BBC

Others said the study wasn't strong enough for doctors to start recommending aspirin. I definitely think we wouldn't want to make any treatment decisions based on this study," said Dr. Raymond DuBois, a cancer prevention specialist who is provost of the University of Texas M.D. Anderson Cancer Center. One concern is that the studies were designed to look at cardiovascular risks, so the groups of people being compared may differ on things that affect cancer risk, such as family history of the disease. DuBois also questioned drawing conclusions about people's cancer risk beyond the several years they were tracked. USAToday
Aspirin, if taken in significant doses and if the individual suffers from certain conditions or has a specific genetic background, is toxic, can cause bleeding in the stomach in about one person per 1,000 and can even cause fatal hemorrhagic strokes. Jerusalem Post
"This is a dramatic thing to claim, and aspirin can be potentially harmful -- this isn't a trivial drug," said Dr. Derek Raghavan, chairman of the Taussig Cancer Institute at the Cleveland Clinic. Raghavan says, "There's really no reason for people to rush off to the doctor and say 'Should I be on aspirin?' " He says it will take time to determine if the conclusions drawn from the eight trials the study examined hold up to further scientific scrutiny. Dr. Neal Meropol, chief of the division of hematology and oncology at University Hospitals Case Medical Center, says the study adds to a growing body of research suggesting a link between daily aspirin use and decreased risk of cancer death -- particularly colon cancer -- but agrees that recommending daily aspirin is premature. The biggest drawback to the Lancet paper, both doctors say, is that it pulled data from eight studies that were not designed to look at cancer deaths as a primary outcome. Most of these studies examined the effects of aspirin use on cardiovascular disease. Data about death from cancer was gathered after the fact -- what is called a post-hoc analysis. "If you suddenly go back 20 years later and look at the data, it's tempting to say the result is because of the drug," says Raghavan. Sometimes, he says, the result is because of a systematic error -- because, for example, everyone in the trial who smoked or was obese (known cancer risk factors) by chance ended up in the arm that got the placebo pills, skewing the outcome. "Until these analyses have been done, I think it's very premature to try and advise people. There's a reason statisticians say 'beware the post-hoc analysis.' "Despite the caution, both doctors say the Lancet study is good cause for optimism.

Aspirin should be thought of in the same context as lifestyle changes such as diet and exercise which can help to preserve health” BBC
Professor Peter Elwood, Cardiff UniversityThey found that "all cause mortality" was reduced by 10 per cent for those taking a 75mg dose of the drug. Daily Telegraph 
Advocates believe that its active ingredient is akin to a vitamin that almost everybody should take, as our modern diet does not provide it. It is thought that it works in cancer because it boosts the body's ability to root out, repair or kill rogue cells that can develop into cancer. Daily Telegraph 
Prof Alastair Watson, Professor of Translational Medicine at the University of East Anglia, said the study was a very important development. "It is further proof that aspirin is, by a long way, the most amazing drug in the world," he said. Daily Telegraph 
Cancer Research UK described the study as "promising". But the charity warned that patients should consult their GP before deciding to take aspirin daily because of the drug's side effects.  
A spokesman for the National Institute for Health and Clinical Excellence (NICE) said it would take into account the new evidence when reviewing it guidelines. "We do review and update all our guidance on a regular basis, and if there is new evidence that we think might change any of our existing recommendations, then we will take that into account, " he said. Daily Telegraph 
A Department of Health spokesman said: "We welcome this addition to the evidence base and note that more research is required before clear conclusions can be drawn on the implications for clinical practice." Daily Telegraph 

Rothwell and his colleagues have already shown that daily aspirin cuts death rates from colorectal cancer by more than a third. For the study published today, they examined all the data they could find from well-conducted trials that had assessed the use of aspirin against a control drug and had recorded deaths from cancer. Guardian
In eight trials involving more than 25,000 patients, they found there were 21% fewer deaths after five years among those who took a daily aspirin tablet, compared with those who did not. The effect was most noticeable in gastrointestinal cancers, where deaths dropped by 54%. Guardian
Patients in aspirin trials 20 years ago were still 20% less likely to die of a solid tumour and 35% less likely to die of gastrointestinal cancer. Guardian
They found that the effects of the aspirin seemed to kick in for pancreatic, brain, oesophageal and lung cancer (generally not the sort triggered by smoking) after patients had been taking it for five years or more. For stomach and colorectal cancer, the effects were seen after 10 years and for prostate cancer after 15 years. After 20 years, the risk of death from prostate cancer was reduced by 10%, for lung cancer by 30%, for colorectal cancer by 40% and for oesophageal cancer by 60%. Guardian
The scientists believe the benefits may be even greater than they could establish. The impact on pancreas, stomach and brain cancers was difficult to quantify exactly because of smaller numbers of deaths, they say. There could be an effect in breast and ovarian cancers, but there is not enough trial data to prove it. Guardian
Prof Peter Elwood, a medical epidemiologist who carried out the first randomised trial of aspirin in heart attack patients, said the increased risks of a stomach bleed were relatively small – about one patient per 1,000 per year. "But there is no increase in deaths from bleeding," he said. "Aspirin appears to be increasing the less serious bleeds." Guardian
Against that, he said, a substantial survey in south Wales showed that 80% of men over 50 already had a high enough risk of heart attack or stroke to justify taking aspirin under all existing guidelines. Guardian
It is already taken by millions to protect against heart attacks and strokes and has an established role in preventing diabetes, dementia, pregnancy complications and pain. Scientists stopped short of recommending it be added to the water supply but declared it was "the most amazing drug".
The latest positive findings on cancer had shifted the balance in favour of mass medication of the population, but it was still too soon to recommend everyone take it, they said. Independent

The problem with aspirin is that in a small number of people it is an irritant to the stomach causing indigestion, nausea and sometimes bleeding. Thousands of people end up in hospital every year with bleeding and ulcers caused by aspirin and similar painkillers. The risk, though small, has to be set against the likely benefit and has prevented its wider use. Independent
It cuts the risk of heart disease and stroke and has been prescribed for decades to people who have had one heart attack in order to prevent a second. But because of the bleeding risk it is not recommended as a preventive measure against a first heart attack. Independent
With the added benefit against cancer, the balance may now need to be reassessed. Professor Rothwell said: "Previous guidelines have rightly cautioned that in healthy middle-aged people the small risk of bleeding on aspirin partly offsets the benefit from prevention of strokes and heart attacks, but the reductions in deaths due to several common cancers will now alter the balance for many people." Independent
Aspirin thins the blood making it harder to form clots which could cause a heart attack or stroke, providing protection against these conditions. Its impact on cancer is less well understood. As an anti-inflammatory, it may curb the spread of the disease by reducing inflammation, which is a key factor in cancer development. Independent
A further theory is that an aspirin helps replace a missing constituent from our diet. Plant salicylates, similar to the active ingredient in aspirin, have reduced since we started growing crops with pesticides and fertilisers. The daily pill may help restore the body's natural balance. Independent
If people are going to take a low dose 75mg daily aspirin, to gain the maximum lifetime benefit they should start in their late 40s or early 50s and continue for 20 to 30 years, Professor Rothwell said. After five to ten years the results suggest overall deaths from all causes (including internal bleeds) would be 10 per cent lower, and the benefit would grow as the years advanced. Independent
The conditions aspirin treats Independent
* Arthritis
* Bladder cancer
* Bowel cancer
* Brain cancer
* Breast cancer
* Dementia
* Diabetes
* Fevers
* Gum disease
* Headaches
* Heart disease
* Lung cancer
* Migraines
* Oesophageal cancer
* Pain
* Pancreatic cancer
* Pre-eclampsia
* Prostate cancer
* Stomach cancer
* Strokes
One of the most striking things about the study is the nature of the cancers involved. Tumours of the brain, lungs and gut are, in the words of Professor Rothwell, ‘the cancers that you really don’t want to get’. Virtually incurable, the brutal reality is that most people who get these diseases die, and quite quickly. Daily Mail 

As a science journalist Michael Hanlon says 'I am not sure I have come across anything quite so dramatic in terms of potential health benefits in my career.' Wonder drugs come and go, but this seems to be the real deal. Aspirin, it seems, has the potential to slash the rates of some of the worst cancers, which are responsible for prematurely ending the lives of tens of thousands of middle-aged people every year. It is hard to imagine any expensive new drug or surgical technique having such a dramatic impact.

Of course there are caveats. Aspirin can cause stomach bleeding and people with a history of gastrointestinal problems, particularly ulcers, should either avoid aspirin or only take it in combination with anti-acid drugs.
In fact, simply drinking a glass of milk with your aspirin may be enough to mitigate the side-effects in the vast majority of people and may even boost the anti-cancer effects.

So how does it work? Aspirin has been around for more than 100 years (in fact the pain-relieving effects of willow bark, a natural source of salicylate chemicals, have been known about for millennia) and it has become something of a medical myth that no one understands how aspirin does it.

In fact, aspirin’s role in protecting against heart attacks and stroke is now relatively well-understood. It thins the blood, reducing the likelihood of clotting and its anti-inflammatory effect, caused by the inhibition of an enzyme called Cox-2 which normally produces inflammatory chemicals implicated in heart disease and stroke. The anti-inflammatory effect also minimises the risk of damage to blood vessels and the tissues surrounding them.

pugh cartoon
But how it prevents cancer is more mysterious. There is a suggestion that aspirin may help repair damaged DNA directly. Inflammation is thought to be a key process in the formation of tumours as well as heart disease. And salicylate appears to assist ‘apoptosis’, or programmed cell death, of cells which might grow into tumours.

It is quite possible that other anti-inflammatory drugs, such as ibuprofen, will be found to have similarly beneficial effects.

In fact, aspirin’s anti-cancer properties may, at least in part, help explain one of the biggest mysteries of medicine – the modern cancer epidemic. In rich countries the lifetime risk of developing cancer now stands at 40 per cent and cancer rates are rising in poor countries as well. Until recently, it was commonly assumed that much if not all of this rise could simply be explained by the fact that we are living longer – cancer is mostly a disease of old age – and better diagnosis.

But some recent studies show that we really are seeing a dramatic increase in the incidence of cancer. When scientists at Manchester University examined hundreds of Ancient Egyptian mummies they found only one obvious case of the disease in the ancient tissues. Cancer rates have been rising dramatically even since the advent of modern medicine and the decline in death rates seen in the last 100 years.

Many point the finger at pollution, the modern diet and perhaps lack of exercise as the cause. Our bodies are bombarded with thousands of synthetic chemicals, from pesticides and air pollutants to food additives and hormone-tainted meat and water that were simply absent in the pre-industrial world.

But there is another intriguing suggestion: as well as introducing various artificial chemicals into our bodies, modern farming techniques are known to strip salicylates from the plants we eat, the natural chemical that forms the basis of aspirin and which plants evolved as a natural protector against diseases.

In the wild, plants produce large quantities of salicylate, to help them repair after damage by pests or severe weather. Our desire for perfect, shiny fruit and vegetables means we protect our food crops from the ravages of nature, and so their flesh is poor in what is being dubbed by some ‘Vitamin S’.

So it could be that part of the reason that we get more cancer is that our diet is salicylate-deficient – and taking aspirin helps remedy this.  Interestingly this Lancet study provides an – indirect – boost for the organic food lobby.

So should we all go out and start taking aspirin? Should we add it to the water supply or to our bread? It is actually quite hard to avoid these dramatic conclusions, although all the scientists involved in this study are naturally cautious. 

‘That’s up to other people,’ says Prof. Rothwell. The problem, as ever, would be that if everyone started taking aspirin tomorrow some people would die (of bleeding) as a result, but we would never notice the people who did NOT get cancer 20 years down the line. There would, perversely and inevitably, be an anti-aspirin backlash.

But if you are middle-aged, have any family history of cancer or heart disease and no history of gastric problems and have a strong desire not to die in your 50s or 60s of a nasty cancer, it would seem to be something of a no-brainer.

Professor Rothwell, aged 46 with three young children, takes aspirin. So do many thousands of other medics and scientists – and this before the news of the cancer study broke.

The irony about aspirin is that were it to be discovered today, it would almost certainly not be licenced – clinical trials would reveal the side effects long before the much more dramatic benefits became clear, and no drug firm would touch the stuff with a bargepole.

It seems we have the most robust attitudes of an earlier age to thank for the fact that you can go and buy the most amazing drug in the world for a penny a pop. 

Read more:

The effects were seen even at a low dose of 75mg a day, about a quarter of that contained in a standard pill taken to relieve headache. For cancers of the pancreas, oesophagus, brain and lungs, it took at least five years of daily aspirin to see a reduction in deaths, ten years for stomach and bowel cancer and fifteen years for prostate cancer. Two months ago Professor Rothwell’s team showed that a daily low dose of aspirin can reduce death rates from bowel cancer by more than a third, while this year scientists in the US reported that the same low dose cut the risk of men developing prostate cancer by up to 30 per cent.They found that for those who had taken aspirin for several years the 20-year risk of dying of all solid cancers was cut by 20 per cent, and by 35 per cent for stomach and bowel cancers.
The 20-year risk of death was reduced by about 10 per cent for prostate cancer, 30 per cent for lung cancer, 40 per cent for bowel cancer and 60 per cent for oesophageal cancer.They found that for those who had taken aspirin for several years the 20-year risk of dying of all solid cancers was cut by 20 per cent, and by 35 per cent for stomach and bowel cancers.
The 20-year risk of death was reduced by about 10 per cent for prostate cancer, 30 per cent for lung cancer, 40 per cent for bowel cancer and 60 per cent for oesophageal cancer.

So, should I start taking aspirin now?
If you have reached your late forties or fifties, you should consider it, this research suggests. People with a high risk of heart attacks or strokes are already often advised to take aspirin, as are those with a strong family history of bowel cancer, or other cancers that develop early. Times FAQ
If aspirin prevents cancer, why wouldn’t I take it?
Mainly because of the risk of internal bleeding. One in every 2,000-3,000 people suffers serious bleeding every year, and aspirin almost doubles this risk. However, it is less clear that aspirin increases the risk of dying from internal bleeding.
The decision is a personal one — am I willing to risk a nasty injury to make it less likely that I will die of cancer, heart attack or stroke? Times FAQ
In practice, it will help some, do little or nothing for others, and harm a few. The problem is that we still do not have a reliable way of predicting which patient belongs to which group. Dr Mark Porter, Times

NHS Opinion
reposted from:

“A daily dose of the ‘wonder drug’ aspirin is the simplest way to avoid dying from the most common cancers,” says the Daily Express.
This news story is based on a study of data from eight clinical trials in more than 25,000 people, which recorded daily aspirin use and deaths from cancer. In total, there were 674 deaths from cancer during the studies’ follow-up periods. People taking aspirin were less likely to die from cancer than those who weren’t taking aspirin.
Overall, this study was well-conducted and its findings will probably be taken into account with other evidence in the next review of the clinical guidance for cancer prevention. 

On its own, however, the study does not present strong enough evidence for aspirin to be universally recommended. This is because long-term aspirin is associated with a risk of internal bleeding, particularly in the elderly. Different people may also have different levels of benefit.

People who want to start taking aspirin should speak to their GP first. Importantly, the doses examined here were low, at only 75mg a day, which is a quarter of what over-the-counter pills for pain relief contain.

Where did the story come from?

The study was carried out by researchers from the University of Oxford, the University of Edinburgh, the University of Dundee, Kumamoto University, Japan, and the London School of Hygiene and Tropical Medicine. No specific sources of funding are mentioned. It was published in the peer-reviewed medical journalThe Lancet.

The story was reported by a large number of newspapers. The accuracy of the coverage varied, with some newspapers reporting that aspirin reduced the risk of developing cancer, when the study actually only looked at the risk of dying from cancer. Most newspapers sensibly caution that there are risks associated with taking aspirin long term and that people should check with a doctor before starting to take it regularly.

What kind of research was this?

The researchers say that research in animals suggests that aspirin inhibits the occurrence or development of tumours, but the evidence in humans has so far been lacking. Observational studies in people have had conflicting results, with some showing that aspirin reduces the risk of some cancers, but only weaker associations being found in more rigorous studies. There is a similar picture for randomised trials of aspirin for cancer prevention, with some trials finding that aspirin cuts the risk of colorectal cancer, but others finding little evidence of benefit for other cancers.
There have been several clinical trials of aspirin for reducing the risk of vascular events (such as angina). These trials often follow people for several years and reliably include details on the cause of death of any participants. Here, the researchers combined data from these studies to examine which people died from cancer while taking part in these trials.
Combining the results of several studies in this way is a valid approach for searching for associations. It should be noted, however, that none of the original trials were designed to study cancer risk, and some of the included studies did not follow the patients for as many years as others.

As such, these results ideally need confirmation in further research specifically designed to answer the question of whether aspirin can prevent cancer.

What did the research involve?

The researchers identified clinical trials in which any dose of aspirin had been compared with no aspirin, including trials in which aspirin was being compared with another antiplatelet drug or an antithrombotic drug, for example warfarin. Studies were identified from a number of research databases and were selected if they had followed people for an average (median) of at least four years. The researchers then contacted the authors of the original studies to obtain data on individual patients. The analysis was limited to looking at fatal cancers only, as the data for these were more reliable and easier to obtain.
The studies identified by the researchers were:
  • The Thrombosis Prevention Trial (TPT, 5,085 people)
  • The British Doctors’ Aspirin Trial (BDAT, 5,139 people)
  • The UK Transient Ischaemic Attack Trial (UK-TIA, 2,435 people)
  • The Early Treatment Diabetic Retinopathy Study (ETDRS, 3,711 people)
  • The Swedish Angina Pectoris Aspirin Trial (SAPAT, 2,035 people)
  • Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD, 2,539 people)
  • Prevention of Progression of Arterial Disease and Diabetes (POPADAD, 1,276 people)
  • Aspirin for Asymptomatic Atherosclerosis (AAA, 3,310 people)
In all the studies data were available on cause of death during the study, but in the three UK-based studies (TPT, BDAT, UK-TIA) the researchers were able to obtain additional long-term data by checking national death certification and cancer registration databases. Data from individual patients were not available for one trial (SAPAT), so these could not be included in the detailed analyses.

What were the basic results?

In total, there were 674 deaths from cancer in 25,530 trial participants. Pooling data from all eight studies showed that people who were allocated to receive aspirin were significantly less likely to die from cancer than people who were not (odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.68 to 0.92, p=0.003). This represents the 21% reduction in risk or odds of death quoted by the newspapers.

Looking at different types of cancer in the seven studies with individual patient data, the researchers found no association between taking aspirin and risk of death from cancer in patients who had been followed up for five years or fewer. Limiting the analysis to patients with more than five years of follow-up showed a reduction in the odds of death from all cancers combined (hazard ratio (HR) = 0.66, 95% CI 0.50 to 0.87, p=0.003). This association was also observed in the combined data for deaths from all gastrointestinal cancers (HR=0.46, 95% CI 0.27 to 0.77, p=0.003) and all solid tumours (HR=0.64, 95% CI 0.49 to 0.85, p=0.002) in patients with more than five years’ follow-up.
Limiting the analysis to the three UK studies in which additional long-term data were available and patients had received aspirin for at least five years (10,502 patients) confirmed that daily aspirin was associated with a lower risk of all cancers (HR=0.78, 95% CI 0.70 to 0.87, p<0.0001). These patients had been followed for up to 20 years.

How did the researchers interpret the results?

The researchers report that “aspirin reduced the risk of death due to cancer by about 20% during the trials”. They point out that this reduction is mostly due to reduction in deaths after five years of treatment. They point out that the original trials involved different types of people, which suggests that the results should be applicable to the general population. They note that aspirin did not seem to be any more beneficial at doses greater than 75mg a day.


Overall, this study was well-conducted and its findings will probably be taken into account with other evidence during the next review of the clinical guidance for cancer prevention. On its own, however, the study does not present strong enough evidence for aspirin to be universally recommended. When looking at the results, the following should be taken into consideration:
  • The eight studies on which this research is based were originally designed to look at aspirin for the prevention of vascular events (such as stroke). The results are, therefore, not as robust as they would have been had the researchers specifically set out to look at the effect of aspirin on cancer. Clinical trials with this aim may give a better insight and enable researchers to look at cases of cancer and not just deaths from cancer.
  • Although the pooled number of people included from the studies is large, the number of deaths from some types of cancer was comparatively small (although, as expected, this increased with age). To understand the extent to which aspirin is protective against specific cancer types, further clinical trials or prospective studies designed to look at those specific diseases are needed.
  • The authors point out that the original trials didn't include sufficient women for them to assess whether there was any association with breast cancer or any other gynaecological cancers, and this is an area for further research.
With any medicine, there is a balance between the risks and benefits of that treatment, and the benefits need to outweigh the potential harms. The issue here is that taking aspirin increases the risk of internal bleeding, particularly in the elderly. Aspirin benefits people who are at risk of cardiovascular disease, but the benefits for healthy people are still unclear.
People who want to start taking aspirin should speak to their GP first. Importantly, the doses in these studies were low, at only 75mg a day, which is a quarter of what over-the-counter pills for pain relief contain.

Links to the headlines

Small daily aspirin dose 'cuts cancer risk'. BBC News, December 7 2010
Daily dose of aspirin - Times, December 7 2010
Aspirin can reduce cancer deaths by up to 60%. Daily Mirror, December 7 2010
Aspirin can cut cancer. The Sun, December 7 2010
Aspirin stops many cancers. Daily Express, December 7 2010

Links to the science

Rothwell PM, Fowkes FGR, Belch JFF, et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. The Lancet 2010, Early Online Publication, December 7

- purchased (stored on hard drive) by crabsallover

x axis: 5, 10, 15, 20 years

x axis: 5, 10, 15, 20 years

x axis: 5, 10, 15, 20 years

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