Crabsallover has covering the aspirin-anti-cancer link since 2011 when Peter Rothwell peer-reviewed research strongly indicated that taking a daily aspirin could prevent cancers.
"Aspirin is already used by millions to reduce the risk of heart attacks and strokes. But the latest research suggests that the drug could also have a major role in treating and preventing cancer. Cheap and safe, it is the nearest we have to a wonder drug, says Jeremy Laurance. So, should we all be taking it?"
"Dutch researchers reported that a daily aspirin could double the life expectancy of patients with gastro-intestinal cancers"
"In a study presented in Vienna this week [September 2015], Dutch researchers reported that a daily aspirin could double the life expectancy of patients with gastro-intestinal cancers – of the oesophagus, stomach and colon. Among the 14,000 cancer patients studied, regular users of the drug were twice as likely to be alive after four years as those who were not taking it."
"Aspirin can halt the march of any cancer through the body"
"Overall, the research suggests that a daily low dose (75mg) aspirin taken for at least five years in middle age can reduce the risk of developing gastro-intestinal cancers (of the oesophagus, stomach and colon) by around 20 per cent. It also protects against other cancers such as breast, lung and prostate, but the reduction in risk is less pronounced. As a treatment, it may be even more powerful. A review of eight large randomised controlled trials – the gold standard of medical research and stronger evidence than Dr Frouws' “observational” study – involving 25,000 patients taking a low daily dose of aspirin to ward off heart disease – found the drug reduced deaths due to all cancers by more than a fifth (21 per cent)."
"Aspirin makes the blood less able to carry cancer cells."
"Published in The Lancet in 2011, that review was followed by a second one, published in 2012, of five randomised trials, which found that patients with cancer taking a daily aspirin reduced “distant metastasis” – spread to organs such as the brain, liver and lungs, which is usually terminal – by 30-40 per cent... Peter Rothwell, Professor of neurology at Oxford University and doyen of aspirin researchers, who conducted both reviews, said this was powerful evidence. Aspirin can halt cancer's remorseless march through the body (though it does not prevent local spread). And not just specific cancers but any cancer."
"The drug appears to work by making the platelets, one of the constituents of the blood, less “sticky”. As a cancer grows, cells break off and are carried round the body in the blood by the platelets until deposited in a distant organ, where they form a new tumour. By reducing the platelets' stickiness, aspirin makes it harder for them to carry and distribute the cancer cells."
"Critics, however, urge caution before aspirin is recommended for mass medication. They point out that most of the randomised controlled trials cited as evidence of its benefits were not designed to test its anti-cancer effects. Potential dangers may not be apparent from trials involving different patient populations."
In September 2015, several UK newspapers covered research on use of aspirin to enhance cancer survival.
According to the Mail: "Three quarters of people with bowel, stomach or throat cancer were still alive five years later, and aspirin is the 'magic bullet' that should be prescribed as soon as someone is diagnosed."
Can aspirin reduce bowel cancer risk? "Taking two aspirin a week could protect against cancer," reports the Daily Telegraph. The Express suggests we should take it daily.
In a large study, researchers found that aspirin use twice or more per week was associated with a 3% reduction in cancer risk. However, when analysed by cancer type, there was only one significant link – for bowel cancer – with a 19% risk reduction for aspirin use.
Forbes
Taking a low dose of aspirin every day could have the potential to prevent breast cancer or stop it in its tracks.
That was the news over the weekend from the annual meeting of the American Society for Biochemistry and Molecular Biology in Boston, where a team of researchers from the Veterans Affairs Medical Center in Kansas City and the University of Kansas Medical Center presented evidence demonstrating the effects of aspirin against two types of breast cancer.
One of them, so-called “triple negative” cancer, is the most aggressive type of breast cancer and also the most dangerous because it often doesn’t respond to conventional therapies.
FASEB Abstract
Aspirin, a classical non-steroidal anti-inflammatory drug (NSAID) is widely used to reduce pains and fever. Epidemiological and experimental studies suggested that Aspirin use reduces the risk of different cancers including breast cancer and may be used as a chemopreventive agent against breast cancer and other carcinogenesis. These studies have raised the tempting possibility that Aspirin could serve as a preventive medicine for breast cancer. However lack of in-depth knowledge of the mechanism of action of Aspirin reshapes the debate of risk and benefit of Aspirin in prevention of breast cancer. Our aim is to investigate effects of Aspirin on pathophysiological events like epithelial to mesenchymal transition (EMT), migration, stemness of cell in breast cancer cells. Our studies using in vitro and in vivo tumor xenograft model show a strong beneficial effects of Aspirin in prevention of breast carcinogenesis. We find Aspirin not only prevents breast tumor cell proliferation in vitro and tumor growth in xenograft mouse model, it also significantly inhibits other pathophysiological events in breast cancer such as EMT, cell migration as well as reprogramming of stemness in breast cancer cells. Collectively our studies suggest that intake of an ASPIRIN a day might offer additional avenues for breast cancer prevention and treatment.
.. the infrastructure supporting a tumour – its ‘microenvironment’ – is a hot topic in cancer research at the moment. In Cancer Research UK previous post in this series, we looked at how otherwise healthy cells collude to form the blood vessels nourishing the tumour. Today, we’ll tell a story that began in 1863, when a German pathologist called Rudolf Virchow peered down his microscope.
Our body’s immune system forms a defensive shield that any fighting force would be proud of. One of its most powerful weapons is inflammation, a carefully orchestrated manoeuvre designed to eliminate enemies such as bacteria, injured cells and chemical irritants. Without it, we probably wouldn't survive beyond infancy.
But inflammation has a split personality – one that can wreak havoc for those unfortunate enough to experience it. And we now know that inflammation’s dark side is a powerful force in cancer development, where it aids and abets tumour growth and spread around the body.
Hell hath no fury
Let’s start with the way inflammation normally works. Our skin constitutes the first line of defence against microscopic invaders. But whenever this barrier is breached, the wrath of the immune system is unleashed – and things get ugly.
As bacteria and other microbes enter the body though an open wound, cells of the immune system (often referred to as ‘white blood cells’) rush to the site of injury, forming the welcoming committee from hell. This highly trained militia gets to work immediately, showering intruders with toxic chemicals, punching holes in their surface or swallowing them whole.
From the outside, this molecular thuggery manifests in swelling, heat, redness and pain – symptoms that anyone who’s ever scraped a knee will be familiar with.
It’s brutal, but it’s over quickly – it has to be, to minimise collateral damage to healthy tissue. As the enemy is eaten and beaten into surrender, signals urge victorious immune cells to return to base camp. Repair and recovery teams move in to direct the process of healing. Blood vessels sprout. A scab forms. Skin grows. And before long, calm returns and it’s back to business as usual.
The heat is on!
While we might not be able to live without it, too much inflammation can cause serious damage. Chronic, persistent inflammation is behind a host of health problems such as rheumatoid arthritis and psoriasis. And after finding immune cells in tumour samples, Rudolf Virchow was the first to ask whether inflammation might also contribute to cancer.
Unfortunately, he was right – many chronic inflammatory diseases (such as pancreatitis and Crohn’s disease) can increase a person’s cancer risk. And cancers caused by infectious agents (like stomach cancer caused by infection with the bacteria Helicobacter pylori, or liver cancer caused by infection with the hepatitis B or C virus) are characterised by one thing: chronic inflammation.
Rudolf Virchow was the first to link inflammation and cancer
It’s getting hot in here
So how does inflammation lead to cancer? Here’s the current thinking.
When a tiny tumour starts growing from a few rogue cells, it can scavenge enough oxygen and nutrients from its surroundings. But as it grows bigger, demand starts to outstrip supply, and things start getting desperate.
As they struggle to survive, and as they accumulate more and more genetic faults, the cancer cells release chemical signals that lure immune cells called macrophages and granulocytes to infiltrate the tumour.
Once inside the tumour’s inner sanctum, these cells secrete molecules (called cytokines) that kick-start the growth of blood vessels (angiogenesis), which ferry in much-needed oxygen and nutrients.
Other cytokines encourage growth of a sort of cellular ‘pillow’ called the stroma against which the tumour rests. Meanwhile, other inflammatory cells spritz the tumour with molecules (free radicals) that further damage their DNA.Inflammation might also fire the starting gun for metastasis by producing chemicals that help tumour cells nibble through the molecules tethering them to their surroundings.
Taken together, it’s clear that fledgling tumours hijack inflammation and use it to accelerate the progression towards full-blown cancer. As one of our own experts once commented:
“If genetic damage is the match that lights the fire, inflammation may provide the fuel that feeds the flames.”
Stay cool, boy
So how do we turn down the heat? Scientists, including ourown are working on how to dampen inflammation, making it much harder for cancers to flourish. They’re hacking into the molecular circuitry controlling inflammation, looking for ways to hotwire the system with next-generation drugs.
But what if we could manipulate inflammation to prevent cancer developing in the first place?Recentresultssuggestthat the answer might be anything but next-generation. In fact, it’s been around since Hippocrates.
Better known to most of us by its brand name aspirin, acetylsalicyclic acid has been used for over a century to quell inflammation, and there’s now a body of evidence highlighting its potential in cancer prevention. While there’s still a way to go to work out who should take aspirin, how much, and for how long, it’s becoming clear that blocking inflammation will play a big role in cancer prevention and treatment in the future.
Rudolf Virchow will never know that his work sparked an entire field of cancer research but thanks to him, the fight against cancer is hotting up.
More on inflammation and bowel cancer Just a quick one. We’ve written before about the links between inflammation and cancer, and couched a lot of what we’ve written in all sorts of caveats like ‘may’ and...
Inflammation and cancer: Sharpin at the sharp end It’s taken six years, the development of a new experimental technique and a move from Germany to London, but an international team of scientists, including some funded by Cancer Research...
Turning up the heat on cancer PARP inhibitors have made an appearance many times on this blog. Designed to exploit a genetic “Achilles’ heel” in tumours, they’re currently showing promise in clinical trials for breast, ovarian...
Andrew T. Chan, Nadir Arber, John Burn, John Whay-Kuang Chia, Peter Elwood, Mark A. Hull, Richard F. Logan, Peter M. Rothwell, Karsten Schrör, and John A. Baron
Abstract
Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term post-trial follow-up of nearly 14,000 patients from 4 randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about 5 years was associated with a 34% reduction in 20-year CRC mortality. A separate meta-analysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in 4 randomized adenoma prevention trials demonstrated that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least 2 years, there was a = 50% reduction in the risk of CRC commencing 5 years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin’s anticancer effect require further investigation.
The mechanism of action of aspirin for chemoprevention
Possible sites of action of aspirin in the prevention of colorectal cancer. COX-dependent and independent targets of aspirin are likely to be present in both epithelial and stromal cell compartments in colorectal adenomas and cancers. ATLs, aspirin-triggered lipoxins; COX, cyclooxygenase; PGE2, prostaglandin E2; S-1P, sphingosine-1-phosphate.
Reducing Inflammation with statins, aspirin, flu jab cuts cancer and heart disease - David Agus
Fever - we don't know if a fever is good or bad. But fever is caused by inflammation.
3:50s - 5:00 Statins block synthesis of LDL cholesterol, lowered death from heart disease and stroke
JUPITER trial (I assume Agus is talking about this trial) - statins reduced incidence of cancer by 40% in people who don't have high cholesterol, also delayed heart attack and stroke by 12 years. Statins work by reducing inflammation which reduces deposition of cholesterol and also reduces cancer.
5:40 how can we measure inflammation? Types of inflammation - some is causal, other is not. How to optimise bad inflammation?
6:40s - 7:15s Taking a flu jab not only reduces the chances of a nasty flu for 5 days but also reduces the chance of getting cancer or heart disease in 10 years time by reducing inflammation
Aspirin: 8.20s - aspirin reduces inflammation which reduces heart disease and cancer
Should NICE and other UK medical authorities be recommending to doctors that most people in UK between 55-65 years should take a daily 75mg aspirin, as a cancer and heart disease preventative? David Agus is suggesting that public policy in USA should be to encourage aspirin’s use in those for whom the potential benefits would be obvious and the risks minimal. Elsewhere, I've reviewed the case for preventative use of aspirin (90+ links), focussing on research by Peter Rothwell (50+ links) at Oxford.
David B. Agus (wikipedia) is a professor of medicine and engineering at the University of Southern California and the author of “The End of Illness.”
"THE inexorable rise in health care spending, as all of us know, is a problem. But what’s truly infuriating, as we watch America’s medical bill soar, is that our conversation has focused almost exclusively on how to pay for that care, not on reducing our need for it. In the endless debate about “health care reform,” few have zeroed in on the practical actions we should be taking now to make Americans healthier.
An exception is Mayor Michael R. Bloomberg of New York, who is setting new standards that we would do well to adopt as a nation. In the last several years, he’s changed the city’s health code to mandate restrictions on sodas and trans fats — products that, when consumed over the long term, harm people. These new rules will undoubtedly improve New Yorkers’ health in years to come.
Such bold moves prompt a provocative question: when does regulating a person’s habits in the name of good health become our moral and social duty? The answer, I suggest, is a two-parter: first, when the scientific data clearly and overwhelmingly demonstrate that one behaviour or another can substantially reduce — or, conversely, raise — a person’s risk of disease; and second, when all of us are stuck paying for one another’s medical bills (which is what we do now, by way of Medicare, Medicaid and other taxpayer-financed health care programs).
In such cases, encouraging a healthy behaviour or discouraging an unhealthy one, ought to be a matter of public policy — which is why, for instance, we insist on vaccinating children for the measles, mumps, rubella and polio; we know these preventive strategies save lives.
Under that rationale, then, why not make it public policy to encourage middle-aged people to use aspirin?
Developed in 1897 by the German chemist Felix Hoffmann, aspirin, or acetylsalicylic acid, has long proved its value as an analgesic. Two millenniums before that, Hippocrates, the father of modern medicine, used its active ingredient — which he extracted from the bark and leaves of the willow tree — to help alleviate pain and fevers.
Since then, we've gained insight into both the biological mechanism and the effects of this chemical compound. Many high-quality research studies have confirmed that the use of aspirin substantially reduces the risk of cardiovascular disease. Indeed, the evidence for this is so abundant and clear that, in 2009, the United States Preventive Services Task Force strongly recommended that men ages 45 to 79, and women ages 55 to 79, take a low-dose aspirin pill daily, with the exception for those who are already at higher risk for gastrointestinal bleeding or who have certain other health issues. (As an anticoagulant, aspirin can increase the risk of bleeding — a serious and potentially deadly issue for some people.)
New reports about aspirin’s benefits in cancer prevention are just as convincing. In 2011, British researchers [Peter Rothwell - over 50 links on crabsallover blog], analysing data from some 25,000 patients in eight long-term studies, found that a small, 75-milligram dose of aspirin taken daily for at least five years reduced the risk of dying from common cancers by 21 percent.
In March, The Lancet published two more papers bolstering the case for this ancient drug. The first, reviewing five long-term studies involving more than 17,000 patients, found that a daily low-dose aspirin lowered the risk of getting adenocarcinomas — common malignant cancers that develop in the lungs, colon and prostate — by an average of 46 percent. In the second, researchers at Oxford and other centres compared patients who took aspirin with those who didn’t in 51 different studies. Investigators found that the risk of dying from cancer was 37 percent lower among those taking aspirin for at least five years. In a subsection of the study group, three years of daily aspirin use reduced the risk of developing cancer by almost 25 percent when compared with the aspirin-free control group.
The data are screaming out to us. Aspirin, one of the oldest remedies on the planet, helps prevent heart disease through what is likely to be a variety of mechanisms, including keeping blood clots from forming. And experts believe it helps prevent cancer, in part, by dampening an immune response called inflammation.
So the question remains: given the evidence we have, why is it merely voluntary for physicians to inform their patients about a health care intervention that could not only help them, but also save untold billions in taxpayer dollars each year?
For some men over the age of 45 and women over 55, the risks of taking aspirin outweigh any benefits — and patients should talk with their doctors before taking any medication, including something as familiar as aspirin.
But with such caveats in place, it still ought to be possible to encourage aspirin’s use in those for whom the potential benefits would be obvious and the risks minimal. Just as we discourage smoking through advertising campaigns, for example, shouldn't we suggest that middle-aged Americans speak to their doctors about aspirin? Perhaps pharmacists or even health insurance companies should be enlisted to help spread the word about this disease-prevention drug?
The right policy will have to be hammered out, of course. But if we’re going to address the country’s sky-high medical bill, we’re going to have to address the need for Americans to be active in protecting their own health.
Everyone may want the right to use tobacco products and engage in other behaviours that are unequivocally linked with disease — or have the right not to wear a seat belt and refrain from other actions that may protect their well-being. But, if so, should society have the obligation to cover the costs of the consequences?
As the former Supreme Court justice Potter Stewart once said, “There is a big difference between what we have the right to do and what is right to do.” Health care reform should, at long last, focus on the latter."
So the question remains: given the evidence we have, why is it merely voluntary for physicians to inform their patients about a health care intervention that could not only help them, but also save untold billions in taxpayer £££ each year?
Since 2010 I've taken a baby aspirin a day. Google: Rothwell aspirin, Here is why...
ISSUE: NOVEMBER 2012 | VOLUME: 63:11
Benefit of Aspirin as Chemoprevention for Barrett’s May Not Outweigh Risks by Caroline Helwick
San Francisco—There is no evidence that aspirin is beneficial for preventing esophageal adenocarcinoma in people younger than age 55 years. Even for appropriate patients, the benefits emerge only after many years of use and the related risks remain unclear, said Janusz Jankowski, MD, PhD, the Sir James Black professor at the University of Oxford in the United Kingdom.
Dr. Jankowski is chief investigator of AspECT (Aspirin Esomeprazole Chemoprevention Trial), a randomized trial that is currently evaluating the chemopreventive effect of aspirin in patients with Barrett’s esophagus (BE). Some of the controversy may well be resolved by AspECT, which is one of the largest randomized trials involving the upper gastrointestinal (GI) tract ever. Currently, 2,513 patients are being tested to ascertain whether low-dose aspirin versus no aspirin—both in combination with esomeprazole (20 vs. 80 mg)—can reduce cancer risk. Efficacy results are expected in 2019 (ClinicalTrials.gov Identifier: NCT00357682).
Dr. Jankowski reviewed the available evidence for aspirin’s effect in preventing esophageal adenocarcinoma in a lecture at the American Society for Clinical Oncology 2012 Gastrointestinal Cancers Symposium.
When compared with other chemopreventive agents like cyclooxygenase (COX) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin has shown the greatest efficacy in reducing the risk for cancer (20%-30%) and cardiovascular events (25%), at by far the lowest cost (approximately $5 per year), although with a slightly higher risk for upper GI bleeding (2.5%-4% per year).
“Compared with traditional NSAIDs and COX inhibitors, aspirin wins hands down for preventing cancer and cardiovascular disease, but GI bleeds are the biggest side effect,” Dr. Jankowski said. “And this GI bleeding profile is only relevant for aspirin taken alone. If you take another NSAID, the risk is additive.”
Although rare, aspirin also has been associated with a risk for macular degeneration.
“We have to consider when we look at randomized data, that aspirin could be preventing some problems but causing others at a very low frequency,” Dr. Jankowski noted.
Preliminary data from the AspECT trial suggest that 5% of individuals are intolerant to aspirin, meaning that one in 20 will discontinue its use due to effects such as GI upset, skin rash or worsening of asthma. And as patients age, the risk for complications gradually increases and could approach 20% by the age of 70, after 20 years of use, Dr. Jankowski said.
“The big challenge is to see if the 20% to 25% of patients who get a cancer prevention benefit are different from the 20% who may get aspirin-induced complications,” Dr. Jankowski said. “Randomized studies are the only way to fully answer the questions related to the risks and benefits of aspirin as chemoprevention.”
An analysis of individual patient data from randomized trials (Rothwell PM et al. Lancet 2011;377:31-41) concluded that taking aspirin daily (=75 mg) reduced deaths due to common cancers, during and after the trials, in 20% to 25% of subjects. The effect was most pronounced for GI tumors; it was apparent after four years and became significant after 10 years.
“One-fifth to one-quarter of patients taking aspirin for cardiac reasons got a secondary benefit in terms of cancer prevention,” Dr. Jankowski observed. “But, based on the data, you may have to take aspirin for at least 10 years, and maybe 20, to get this benefit, so the side-effect frequency needs to be exceptionally low. And as good as aspirin is, the response rate is just 20% and we still don’t know who the responders will be.”
It also is possible that the preventive effect is smaller, he added, based on his reanalysis of the Rothwell data.
“In our hands, we showed that cancer prevention is not 20% to 25%, but more like 7% to 10% (risk ratio [RR] 0.9; 95% confidence interval [CI], 0.87-1.00]),” he said. “This is crucial. We need to understand the real benefit and risks in order to determine the value, especially as primary prevention.”
From cardiology data it is clear that aspirin use affects cardiovascular events only in persons already at high risk (i.e., the secondary prevention population). A recent paper recapitulated this finding in cancer as well as cardiac disease, Dr. Jankowski noted.
In a meta-analysis of randomized controlled trials involving 100,000 participants followed for a period of six years (Seshasai SR et al. Arch Intern Med. 2012;172:209-216), it was found that aspirin treatment reduced total cardiovascular events by a modest 10%, did not prevent cardiovascular deaths and was associated with a 31% increased risk for nontrivial bleeding events. The investigators concluded that routine use of aspirin for primary prevention is not warranted.
“So, should one take low-dose aspirin?” Dr. Jankowski asked. “At this time, the answer is indefatigably ‘No, you should not,’ unless you have secondary risk factors for cardiac or GI conditions.”
The international Consensus Statements for Management of Barrett’s Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process (BADCAT, Gastroenterology, 2012;143:336-346) confirmed Dr. Jankowski’s conclusions. The group’s consensus is that it is not currently known whether aspirin can prevent the progression of BE and that the inherited genetics of BE has not been clarified. These topics should be a research focus, the group stated.
Early data from the AspECT trial, however, have offered encouraging signs that four years of aspirin treatment may be protective.
“There are not enough data to determine if it prevents cancer, but we see new squamous islands appearing where Barrett’s esophagus was,” said Dr. Jankowski.
“We may have a recommendation regarding aspirin use within the next two years,” he added. “Meanwhile, there is no evidence whatsoever, even with risk factors for cancer or cardiac disease, that a person should take aspirin before the age of 55 years. And we don’t think that taking aspirin after the age of 75 makes sense, based on the need to take it for 10 years to achieve a benefit, and because of the high incidence of side effects at this age. Between the ages of 55 and 75, a patient could take aspirin, but there are still risk–benefit issues and we don’t know who will respond. We need to deal with these issues urgently.”
Prateek Sharma, MD, professor of medicine at the University of Kansas School of Medicine, Kansas City, commented on the findings.
“The majority of esophageal adenocarcinomas originate in patients with Barrett’s esophagus. These patients progress to low-grade dysplasia, high-grade dysplasia, intramucosal carcinoma and finally to invasive carcinoma,” he noted. “Currently, we survey patients with Barrett’s esophagus to detect high-grade dysplasia and early cancer, which can then be treated for cure. We could achieve substantial health care savings if we had an agent that would prevent these conditions.
Although observational studies have generated preliminary data on the ability of certain agents such as aspirin, sulindac and DFMO [difluoromethylornithine) to prevent esophageal cancer, their broad clinical applicability is limited due to their toxicity,” he added. “Further research is needed to identify which subset of patients would benefit from chemoprevention and the dose required, duration of treatment and toxicity.”
"Daily dose of aspirin cuts cancer risk," The Daily Telegraph says. The newspaper reports that a daily dose for the over-60s can "cut cancer risk by 40%".
The story is based on a recent long-term cancer prevention study that included more than 100,000 adults.
Looking at the data as a whole, the researchers found that those who were taking daily aspirin at the start of the study had a very slightly lower risk of dying from cancer over the 11 years of the study. This result was not statistically significant (it could have been a chance result). However, when the researchers restricted the analysis to those who had updated information on their aspirin use throughout the course of the study, they did find a significant 16% reduced risk of death from cancer.
This is not the first time aspirin has been associated with reduced cancer risk. A review of clinical trials published earlier this year also observed a reduced risk of developing cancer with daily aspirin. However, the risk reduction found from the pooled results of those trials was greater (37% reduction) than that found in this study (16%). This may be because this was an observational study and not a trial, so people taking daily aspirin were doing so for cardiovascular disease. Health factors associated with cardiovascular disease may also increase the risk of cancer.
It is important to stress that you should never start taking aspirin on a daily basis without first checking with your GP or pharmacist that it is safe or suitable to do so. Aspirin is not without risks and is known to increase risk of gastrointestinal irritation and bleeding, particularly in the elderly or those with a history of stomach ulcers or bleeding problems. It also should not be taken by people with asthma.
Overall, the current evidence is not strong enough to recommend that everyone take daily aspirin purely for cancer prevention.
Where did the story come from?
This study was conducted by researchers of the Epidemiology Research Program of the American Cancer Society, Atlanta, USA, and was funded by the American Cancer Society.
The study was published in the peer-reviewed Journal of the National Cancer Institute.
The Telegraph’s headline claim that aspirin can “cut cancer risk by 40%” is misleading as this result was found by a different study published in March of this year and not by the study discussed in the news article. The Telegraph does appropriately include quotes from one of the lead authors of the study, Dr Eric Jacobs. The paper says that Jacobs “emphasised people should not take aspirin every day before discussing the potential side effects, such as stomach bleeds, with their doctors”.
What kind of research was this?
This was a prospective cohort study looking at the relationship between daily aspirin use and risk of death from cancer.
A previous systematic review published earlier this year, which pooled data from randomised controlled trials (RCTs), found that using aspirin was associated with a reduction in risk of death from cancer. This cohort further investigated the association between daily aspirin use and cancer mortality.
Although this study included a large number of people who were reliably followed up, it is still not the best way of examining the effects of an intervention (in this case aspirin) for reducing the risks of an outcome (in this case cancer mortality). The best way would be using a randomised controlled trial. The difficulty is that, although many randomised controlled trials of aspirin use have been conducted and were included in the 2012 systematic review, most of these trials were designed to assess the effectiveness of aspirin in preventing cardiovascular events such as heart attack and stroke. That is, the participants were taking aspirin for prevention of cardiovascular disease, not to see whether it would reduce their risk of cancer. Therefore, these trials may not give such reliable risk estimates for the outcome of cancer.
Nevertheless, this large cohort study is valuable in adding to the evidence on the association between aspirin use and cancer outcomes.
What did the research involve?
This was part of the Cancer Prevention Study II (CPS-II) Nutrition Cohort. In 1992, people in the CPS-II trial answered questions about themselves, including medical (such as aspirin use) and behavioural factors. They answered follow-up questionnaires to update information and find out about new cancer diagnoses in 1997 and every two years after.
However, the questions about aspirin use were slightly different in 1992 from those asked in 1997 and after. In 1992 people were asked the average number of days a month they used aspirin during the past year, and the average number of pills taken on those days. In 1997 and onwards people were also asked specifically about use of low-dose (75mg) or higher-dose aspirin. Participants reporting use of aspirin (any dose) on 30 or 31 days a month were considered “daily users”.
Excluding people with a cancer diagnosis in 1997 or before, and those without information on aspirin use, left 100,139 participants (44,360 men and 55,779 women) in this study.
Researchers followed up deaths and cause of death through the US National Death Index to the end of 2008. For 99.3% of deaths that occurred they obtained either death certificates or disease classification codes for the cause of death from the database.
The researchers analysed these deaths according to whether people reported that they took aspirin and, if they did, how long they had been taking it for. They also did a separate analysis looking at current (short-term and long-term), past or occasional users.
What were the basic results?
Most participants were over 60 in 1997 and, at this time, 24% reported daily aspirin use. Almost half of these people taking aspirin (46%) were taking the low dose and most of them were taking one tablet daily, suggesting that it was being used for the prevention of cardiovascular disease.
Daily users were also slightly more likely than non-users to be:
highly educated
former smokers rather than never having smoked
obese
using anti-inflammatory drugs regularly (such as ibuprofen)
Over the 11 years of study follow-up (1997-2008), a total 5,138 (5%) participants died from cancer. In the first analysis, compared with no use, daily aspirin use at the start of the study was associated with slightly reduced risk of dying from cancer, though these risk reductions did not reach statistical significance:
use for less than five years (use in 1997 but not 1992) – non-significant 8% reduction in risk (0.92, 95% confidence interval (CI) 0.85 to 1.01)
use for five or more years (use in 1997 and 1992) – also a non-significant 8% reduction in risk (0.92, 95% confidence interval, 0.83 to 1.02)
There were, however, significant reductions in risk in subsequent analyses that included aspirin information from later questionnaires (including 3,373 cancer deaths). These were thought to provide a more reliable source of data:
use for less than five years (daily use in 2003 but not in both the years 1999 and 2001) – 16% reduction in risk (0.84, 95% confidence interval, 0.76 to 0.94)
use for five or more years (use in 1999, 2001 and 2003) – also a 16% reduction in risk (0.84, 95% confidence interval 0.75 to 0.95)
How did the researchers interpret the results?
The authors say that their results show an association between daily aspirin use and modestly lower cancer mortality. However, the reduction in cancer mortality they record is smaller than that observed with long-term aspirin use in the pooled results of the recent systematic review published in the Lancet (37% risk reduction with more than five years of use).
Conclusion
This study had a large number of participants and the follow-up was reliable. It provides further information that daily aspirin may give a small reduction in risk of dying from cancer.
A cohort study is not the best way of examining the effects of an intervention upon an outcome, as there may be other health or lifestyle factors that differ between those who take aspirin and those who don’t, that might influence their risk of cancer. Also, the study used self-reported questionnaires to assess aspirin use and there may be some inaccuracies in estimates of dose or frequency of use.
The study follows on from a systematic review published earlier this year that had included all randomised trials examining the effect of aspirin in reducing the risk of dying from cancer. The difficulty is that the participants in the clinical trials that were included in this review were taking aspirin for prevention of cardiovascular disease (for example, heart attack or stroke), not to see whether it would reduce their risk of cancer. Therefore, these trials may not give such reliable risk estimates for the outcome of cancer. Similarly, most of the people in the current cohort who were taking daily aspirin also seemed to be doing so for the reason of prevention of cardiovascular disease – not for cancer prevention. Therefore, neither this cohort nor the clinical trials have examined the use of aspirin for cancer prevention, and we don’t know whether the benefits of aspirin outweigh the risks in people without risk factors for cardiovascular disease.
Although aspirin is widely established as an effective treatment for cardiovascular disease, aspirin is not yet recommended as a treatment to prevent cancer as the risks of aspirin might outweigh the benefits. Aspirin can rarely cause serious adverse effects, and is known to increase the risk of stomach irritation and bleeding. Those who may be at higher risk of these complications are the elderly, people who have past history of stomach ulcers, or people who are taking drugs that increase their risk of bleeding or have other medical conditions that increase their risk of bleeding. Aspirin can also cause breathing problems in people with asthma and some people can have allergic reactions to aspirin.
There are many other lifestyle changes that people can make that may reduce their risk of cancer, including giving up smoking, eating a healthy balanced diet and taking regular exercise.
A mass screening campaign for Helicobacter pylori is advocated by Jack Cuzick of London University. Helicobacter pylori can cause stomach bleeds so elimination with antibiotics means that risk of ulcers with aspirin is reduced. After elimination of Helicobacter pylori, everyone between 50-70 years would be recommended to take a daily aspirin to reduce risk of all cancers by 25%.
@35'50s - everyone over 40 should take 75mg Aspirin a day, everyone over 50 years 300mg a day. International Society of Cancer Prevention study (out of date website) due early August @ 37'20s says mass screening would reduce risk of stomach bleeds.
Aspirin and cancer – the picture becomes clearer Posted on March 21, 2012 by Jess Harris
Aspirin has been around for over a century. “Should I be taking aspirin to reduce the risk of dying from cancer?”
This is likely to be the question on many people’s minds today, which sees the publication of three reports on the effects of aspirin on cancer risk, and cancer spread – No 1 and No 2 in the Lancet, and No 3 in sister journal Lancet Oncology.
But before we look at today’s studies, we need to set the scene. Over the last few years, the evidence has been building that regularly taking the simple, cheap drug aspirin could reduce the risk of dying from cancer.
For example, a large study by Peter Rothwell from December 2010 showed that people who took 75 milligrams of aspirin (the same dose as in a ‘junior’ aspirin) every day had a reduced risk of dying from cancer.
But these results didn’t answer all the questions, and we felt it was too early to start recommending that people take low-dose aspirin every day. This is because aspirin’s not a harmless drug. In some people it can cause serious side effects, like internal bleeding.
On top of this, it wasn’t clear what the best dose is, or at what age it’s best to start taking aspirin.
Today’s studies clarify the picture a little, but because of the uncertainties we’re still recommending that people discuss things with their doctor before taking aspirin.
What do the latest studies add? The three studies published today were all led by Professor Peter Rothwell at Oxford University, who’s one of the world’s top aspirin researchers.
The studies looked at data from several large trials of taking daily, low-dose aspirin that aimed to find out aspirin’s effect on heart disease, and also measured how many people were diagnosed with cancer.
Preventing cancer Taken together, the studies provided more information about how aspirin affects the risk of cancer developing in the first place.
Earlier studies had shown that aspirin probably reduces the risk of developing bowel cancer, and some other cancers in the digestive system. But this study showed that, after three years of daily low-dose aspirin, the risk of developing cancer at all dropped significantly in both men and women.
In fact, there were nine cases of cancer in every 1,000 people taking aspirin, compared with twelve cases per 1,000 people not taking it – an absolute reduction of three cases per 1,000 people.
The cancers most strongly prevented were oesophageal, stomach, bowel and lung cancers.
Preventing cancer spreading But a new – and somewhat unexpected – finding from this research is that cancer patients taking aspirin every day appeared to have a reduced risk of their cancers spreading.
In fact, not only were regular aspirin-takers less likely to be diagnosed with a cancer that’d already spread, but (compared to non-aspirin takers) patients on aspirin diagnosed with early localised cancers had a lower chance that their cancer would spread later on.
And it also hints that aspirin could be useful for people who’ve already been diagnosed with cancer – though, importantly, this will depend on the individual case.
This is because some cancer patients will also have a higher than normal risk of bleeding, because of their cancer or treatment. So it’s important that people with cancer talk to their doctors rather than deciding to take aspirin by themselves.
Because of these two effects (the reduced risk of getting cancer, and the prevention of it spreading) , the research also suggested that regularly taking aspirin reduced the risk of dying from cancer by nearly 40 per cent after people had been taking it for 5 years.
Balance of risks and benefits
Finally, and importantly, the studies looked into the balance of benefits and harms of taking aspirin in a healthy population. This is critical, because if people are considering taking aspirin for preventing cancer, we’ve got to be very sure about whether it does good or harm overall.
As the graph below shows, over time, the benefit – lowering cancer risk – increased, while the risk of serious side effects, like internal bleeding, got smaller. Crucially, in the first three years of taking aspirin, the risk of serious internal bleeding was much higher in aspirin-takers than those who weren’t on the drug:
This risk went down over time, and after 5 years of taking the drug, the risk of internal bleeding was back at the same level as people who weren’t on the drug.
Overall, the risk of all the outcomes combined – cancer, serious internal bleeding and major heart and circulatory problems – was lower in the aspirin group. That seems to show the balance could be tipping to the benefit side. Here are the raw numbers:
But that’s not the only consideration – if people stop taking aspirin daily, their risk of a stroke goes up.
And certain people definitely shouldn’t take aspirin, because they’re at higher risk of serious complications. That includes people with asthma, stomach ulcers, haemophilia, or anyone taking other drugs that might interact badly with aspirin.
So what should I do? The first and most important thing is that if you’re considering starting to take aspirin daily, discuss it with your GP first, or your cancer specialist if you’ve been diagnosed with cancer.
In particular, there might be a reason why taking aspirin every day would be a bad idea for you personally – despite what the overall evidence says. And it’s worth discussing the benefits and harms, taking into account your own and your family’s medical history.
And if you do get the go ahead from your own doctor, you should make sure you don’t take aspirin on an empty stomach.
Today’s results are encouraging, and add to our understanding of the effects of taking aspirin daily. But there are still questions to answer. For example:
What is the optimal period of time to be taking aspirin for? At what age does the biggest benefit and smallest risk occur? Who is most likely to benefit, and who is most likely to get side effects? And how can we minimise the risk of a stroke when people stop taking the drug? Cancer Research UK scientists are running trials at the moment that aim to answer some of these questions.
And we’d also like to see some analysis and advice from the Governement about whether aspirin should be recommended more widely.
Until this is the case, taking aspirin should still be a decision you take in consultation with your doctor.
Jess
Cancer Research UK Chief Medical Officer, Professor Peter Johnson:
Search for 'Peter Rothwell' on this blog for more trials results linking aspirin to cancer reduction.
Further research by Peter Rothwell - digging around in "old archives in dusty basements" indicates:-
aspirin can reduce cancer growth or metastasis
aspirin works to prevent metastasis in the same way it reduces heart attacks and strokes. Aspirin works by platelet inhibition. There are far fewer platelets roaming the body assisting cancer to metastasis
aspirin might help in treatment of some cancers
stopping of aspirin after diagnosis of cancer could be detrimental
treat 10,000 cancer patients with aspirin for cost of one treated with Herceptin
Peter Rothwell, 1980—90: a lack of direction and an undistinguished career as a medical student. Peter Rothwell, 1991—2011: award-winning Director of the Stroke Prevention Research Unit at the University of Oxford, UK, and author of over 300 publications that have transformed the landscape of stroke prevention. He is a man who takes some figuring out. Reflecting on Rothwell's stratospheric rise to a giant of neurology, Charles Warlow, Rothwell's mentor and Professor of Medical Neurology at Edinburgh University, says simply, “he's a phenomenon”.
The past two decades have seen Rothwell show which patients benefit from carotid endarterectomy to prevent stroke, that there is a high risk of major stroke after transient ischaemic attack (TIA) and minor stroke, and that there are enormous benefits from urgent treatment to reduce this risk. This work called for greater urgency in investigating and treating minor stroke and TIA, which had previously been thought of as fairly benign conditions, so Rothwell developed a risk scoring system to enable clinicians to predict the likelihood of stroke in the first few days after TIA.
More recently, Rothwell has found that variability in blood pressure is at least as important as mean blood pressure for predicting the risk of stroke and that some of the most effective antihypertensive drugs reduce variability, as opposed to simply reducing mean blood pressure. Along the way, he has proved that the statistical basis of the “usual blood pressure hypothesis” approach to diagnosis and treatment of hypertension is invalid, and has still found time to show that aspirin can reduce mortality due to several major cancers.
Rothwell's record is extraordinary by any measure, but juxtaposed with his early years as a medical student it almost defies belief. Born to a 16-year-old single mother in a poor area of Liverpool and adopted and brought up by a family in Manchester, Rothwell got good grades at school. But, as the first person from his family to go to university, he had little sense of what kind of career he wanted. “I didn't have sufficient knowledge or originality to think of anything else to do, so I did medicine”, he says. Rothwell ended up at Edinburgh University, where he cheerfully admits to not being “particularly academic”. Far more interested in indulging his passion for mountaineering than attending medical lectures, “he was completely obscure as a student”, says Warlow. “And he became even more obscure when he went off to do his senior house officer [SHO] jobs in Middlesbrough.”
It was during his time working at the intensive therapy unit in Middlesbrough that Rothwell gathered data, largely unsupervised, on the endocrine response to critical illness, which he then wrote up for his MD. “That was extraordinary”, says Warlow. “I mean, no SHO collects data for an MD. Somehow or other, Pete just did it. And it's been just like that ever since. He just gets on and does it, and he does it at the most extraordinary speed.” A move back to Edinburgh as a clinical research fellow, and into Warlow's tutelage followed. “He got me interested in stroke and was an inspirational supervisor”, he says of Warlow. “And stroke has been my main focus since then”. His time with Warlow also laid the foundations for Rothwell's appreciation of the importance of asking the simple questions about how to best do medicine in the real world, and gave him the confidence to challenge the consensus. Louise Silver, Research Co-ordinator at the Stroke Prevention Research Unit, Oxford, which Rothwell established in 2000, explains that these are virtues that he is passing on to his own fellows. “His focus on clinical research, and how this can directly impact patient care, certainly gives myself and others a feeling that all our hard work has and will make a difference”, she says.
In an age when so many researchers fall over themselves to jump on the latest bandwagon, Rothwell is something of an iconoclast. “Medical research is so fashion conscious”, he says. “Everyone suddenly becomes geneticists, then 10 years later they're stem cell researchers.” By contrast, Rothwell's willingness to eschew fads has helped him reap a bumper crop of what he calls, for want of a better term, low-hanging fruit. “There's so much simple clinical research that should have been done 50 years ago but wasn't”, he explains. “The work we've done on working out the prognosis of TIAs and minor stroke should have been done years ago but wasn't.” The same can be said of his work on blood pressure variability and risk of stroke or the non-vascular effects of aspirin. “It's all simple stuff”, he insists.
For someone whose work has garnered such acclaim, Rothwell's modesty is striking. But beneath the softly spoken self-effacement, you get a sense of the kind of strength of character that has helped propel him so far, so fast. Moving to Oxford having been an undergraduate elsewhere certainly requires mental fortitude, and despite “still feeling like a new boy”, he has flourished. “He's quite tough you know, Pete”, Warlow attests. Still only 47, Rothwell is showing no signs of slowing down, and wants to carry on the Oxford Vascular Study, which he established in 2002, for another 20 years “to really understand what's happening to vascular disease over time”. He also expects variability in blood pressure to come further to the fore, especially in relation to dementia. And he hints that aspirin (he takes it) might still have a few new tricks up its sleeve. Considering what he has achieved in the past 20 years, the possibilities for the next 20 seem endless.
