Health Benefits of Aspirin - General Cancer Benefits

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Aspirin reverses obesity cancer risk

Research has shown that a regular dose of aspirin reduces the long-term risk of cancer in those who are overweight in an international study of people with a family history of the disease.

The study, conducted by researchers at Newcastle University and the University of Leeds, UK, is published in the Journal of Clinical Oncology.

They found that being overweight more than doubles the risk of bowel cancer in people with Lynch Syndrome, an inherited genetic disorder which affects genes responsible for detecting and repairing damage in the DNA. Around half of these people develop cancer, mainly in the bowel and womb.

However, over the course of a ten year study they found this risk could be counteracted by taking a regular dose of aspirin.

Professor Sir John Burn, professor of Clinical Genetics at Newcastle University who led the international research collaboration, said: "This is important for people with Lynch Syndrome but affects the rest of us too. Lots of people struggle with their weight and this suggests the extra cancer risk can be cancelled by taking an aspirin.

"This research adds to the growing body of evidence which links an increased inflammatory process to an increased risk of cancer. Obesity increases the inflammatory response. One explanation for our findings is that the aspirin may be supressing that inflammation which opens up new avenues of research into the cause of cancer."

The randomised controlled trial is part of the CAPP 2 study involving scientists and clinicians from over 43 centres in 16 countries which followed nearly 1,000 patients with Lynch Syndrome, in some cases for over 10 years.

937 people began either taking two aspirins (600 mg) every day for two years or a placebo. When they were followed up ten years later, 55 had developed bowel cancers and those who were obese were more than twice as likely to develop this cancer -- in fact 2.75 times as likely. Following up on patients who were taking two aspirins a day revealed that their risk was the same whether they were obese or not.

The trial was overseen by Newcastle Hospitals NHS Foundation Trust and funded by the UK Medical Research Council, Cancer Research UK, the European Union and Bayer Pharma.

Professor John Mathers, Professor of Human Nutrition at Newcastle University who led this part of the study said: "For those with Lynch Syndrome, we found that every unit of BMI above what is considered healthy increased the risk of bowel cancer by 7%. What is surprising is that even in people with a genetic predisposition for cancer, obesity is also a driver of the disease. Indeed, the obesity-associated risk was twice as great for people with Lynch Syndrome as for the general population.

"The lesson for all of us is that everyone should try to maintain a healthy weight and for those already obese the best thing is to lose weight. However, for many patients this can be very difficult so a simple aspirin may be able to help this group.

Professor Tim Bishop from the University of Leeds who led on the statistics for the study added: "Our study suggests that the daily aspirin dose of 600 mg per day removed the majority of the increased risk associated with higher BMI. However, this needs to be shown in a further study to confirm the extent of the protective power of the aspirin with respect to BMI.

However, Professor Burn advises: "Before anyone begins to take aspirin on a regular basis they should consult their doctor as aspirin is known to bring with it a risk of stomach complaints including ulcers.

"But if there is a strong family history of cancer then people may want to weigh up the cost-benefits particularly as these days drugs which block acid production in the stomach are available over the counter."

The international team are now preparing a large-scale follow-up trial and want to recruit 3,000 people across the world to test the effect of different doses of aspirin. The trial will compare two aspirin a day with a range of lower doses to see if the protection offered is the same.

Information on the next trial can be found at http://www.capp3.org

Mechanism

The researchers believe the study shows that aspirin is affecting an underlying mechanism which pre-disposes someone to cancer and further study is needed in this area. Since the benefits are occurring before the very early stages of developing a tumour -- known as the adenoma carcinoma sequence -- the effect must be changing the cells which are predisposed to become cancerous in later years.

One possibility is that a little recognised effect of aspirin is to enhance programmed cell death. This is most obvious in plants where salicylates trigger this mechanism to help diseased plants contain the spread of infection.

"We may be seeing a mechanism in humans whereby aspirin is encouraging genetically damaged stem cells to undergo programmed cell death, this would have an impact on cancer," says Sir John.

Aspirin may fight cancer by slowing DNA damage

Aspirin is known to lower risk for some cancers, and a new study led by a UC San Francisco scientist points to a possible explanation, with the discovery that aspirin slows the accumulation of DNA mutations in abnormal cells in at least one pre-cancerous condition.

"Aspirin and other non-steroidal anti-inflammatory drugs, which are commonly available and cost-effective medications, may exert cancer-preventing effects by lowering mutation rates," said Carlo Maley, PhD, a member of the UCSF Helen Diller Family Comprehensive Cancer Center, and an expert on how cancers evolve in the body over time.

In the study, published June 13, 2013 in the online journal PLOS Genetics, Maley, working with gastroenterologist and geneticist Brian Reid, MD, PhD, of the Fred Hutchinson Cancer Research Center, analyzed biopsy samples from 13 patients with a pre-cancerous condition called Barrett's esophagus who were tracked for six to 19 years. In an "observational crossover" study design, some patients started out taking daily aspirin for several years, and then stopped, while others started taking aspirin for the first time during observation. The goal was to track the rate of mutations in tissues sampled at different times.

The researchers found that biopsies taken while patients were on an aspirin had on average accumulated new mutations about 10 times more slowly than biopsies obtained during years when patients were not taking aspirin.

"This is the first study to measure genome-wide mutation rates of a pre-malignant tissue within patients for more than a decade, and the first to evaluate how aspirin affects those rates," Maley said.

Gender and ethnic distribution of study patients reflected the known demographics of esophageal cancer, which predominantly affects, white, middle-aged and elderly men, he said. Barrett's esophagus only occasionally progresses to esophageal cancer.

Cancers are known to accumulate mutations over time much more rapidly than normal tissue, and different mutations arise in different groups of cells within the same tumor. The acquisition of key mutations ultimately allows tumor cells to grow out of control, and diversity within a tumor may foster drug resistance, a phenomenon that is a major focus of Maley's research.

Maley plans to test a hypothesis that may explain the results — that aspirin's lowering of mutation rates is due to the drug's effect of reducing inflammation. Inflammation, a response of the immune system, in recent years has been recognized as a hallmark of cancer. Maley said that less inflammation may result in less production within pre-cancerous tissue of oxidants known to damage DNA, and may dampen growth-stimulating signaling.

For the duration of the study, the rate of accumulation of mutations measured in the biopsied tissue between time points was slow, even when patients were not taking aspirin, with the exception of one patient. While mutations accumulated at a steady rate, the vast majority of mutations arose before the abnormal tissue was first detected in the clinic, the researchers concluded.

These findings are consistent with the fact that although Barrett's esophagus is a significant risk factor for esophageal cancer, the vast majority of cases do not progress to cancer, Maley said.

In the one patient who later went on to develop cancer, a population of cellular "clones" with a great number of mutations emerged shortly before he started taking aspirin.

More studies are needed to further explore the link between non-steroidal anti-inflammatory drugs, mutation rates and the development of invasive cancer, Maley said. He plans to continue studying Barrett's esophagus and esophageal cancer, and to expand his research to investigate lung cancer.

Rather than aiming to kill the most tumor cells, it may be better to try to halt or slow growth and mutation. Current drug treatments for cancer may in many cases hasten the emergence of cancer that is more difficult to eradicate, according to Maley. The capability to mutate frequently allows tumors to become resistant to drug treatment, he said. A better-adapted mutant can begin to spin off a population of genetic clones that survives and grows, while poorly adapted tumor cells die off.

Aspirin for Primary Prevention in Men When Cancer Mortality Benefit Added

While aspirin has been shown to be effective in preventing heart attacks in men, it also increases the risk of gastrointestinal bleeding and possibly stroke, even at low doses. As such, national guidelines suggest that aspirin be used for prevention only in men at higher risk for cardiovascular events, so that the benefits of aspirin are greater than its adverse effects.

Recent data suggest that aspirin may also be effective for reducing cancer deaths. Would the possible combined health benefits of reducing heart attacks and cancer outweigh the risks of gastrointestinal bleeding and stroke for middle-aged men?

A research team, including UNC scientists, reports that including the positive effect of aspirin on cancer mortality influences the threshold for prescribing aspirin for primary prevention in men. The benefit of aspirin for cancer mortality prevention would help offset the risks and thus lower the age and increase the number of men for whom aspirin is recommended. Their results were published in the June 2013 issue of the Journal of General Internal Medicine.

Michael Pignone, MD, MPH, and study lead author, says, “We found that including a risk reduction for cancer deaths had a substantial impact on the overall benefits of aspirin, especially for early middle-aged men from 45 to 55 years of age. Based on this effect, several million men who were not previously good candidates for aspirin prevention would now become eligible.

The U.S. Preventive Services Task Force, of which Dr. Pignone is a recently appointed member, recommends aspirin for primary prevention in men “when the potential benefit of a reduction in myocardial infarctions outweighs the potential harm of an increase in gastrointestinal hemorrhage.” This recommendation was issued in 2009, before the potential benefits for cancer reduction were recognized.

Study: daily aspirin linked to lower cancer mortality

A large new observational study finds more evidence of an association between daily aspirin use and modestly lower cancer mortality, but suggests any reduction may be smaller than that observed in a recent analysis. The study, appearing early online in the Journal of the National Cancer Institute (JNCI), (August, 2012) provides additional support for a potential benefit of daily aspirin use for cancer mortality, but the authors say important questions remain about the size of the potential benefit.

A recent analysis pooling results from existing randomized trials of daily aspirin for prevention of vascular events found an estimated 37% reduction in cancer mortality among those using aspirin for five years or more. But uncertainty remains about how much daily aspirin use may lower cancer mortality, as the size of this pooled analysis was limited and two very large randomized trials of aspirin taken every other day found no effect on overall cancer mortality.

For this study, American Cancer Society researchers led by Eric J. Jacobs, Ph.D., analyzed information from 100,139 predominantly elderly participants in the Cancer Prevention Study II Nutrition Cohort who reported aspirin use on questionnaires, did not have cancer at the start of the study, and were followed for up to 11 years. They found daily aspirin use was associated with an estimated 16% lower overall risk of cancer mortality, both among people who reported taking aspirin daily for at least five years and among those who reported shorter term daily use. The lower overall cancer mortality was driven by about 40% lower mortality from cancers of the gastrointestinal tract (such as esophageal, stomach, and colorectal cancer) and about 12% lower mortality from cancers outside the gastrointestinal tract.

The reduction in cancer mortality observed in the current study is considerably smaller than the 37% reduction reported in the recent pooled analysis of randomized trials. The authors note that their study was observational, not randomized, and therefore could have underestimated or overestimated potential effects on cancer mortality if participants who took aspirin daily had different underlying risk factors for fatal cancer than those who did not. However, the study's large size is a strength in determining how much daily aspirin use might lower cancer mortality.

"Expert committees that develop clinical guidelines will consider the totality of evidence about aspirin's risks and benefits when guidelines for aspirin use are next updated," said Dr. Jacobs. ‘

"Although recent evidence about aspirin use and cancer is encouraging, it is still premature to recommend people start taking aspirin specifically to prevent cancer. Even low-dose aspirin can substantially increase the risk of serious gastrointestinal bleeding. Decisions about aspirin use should be made by balancing the risks against the benefits in the context of each individual's medical history. Any decision about daily aspirin use should be made only in consultation with a health care professional."

Aspirin's potential role in reducing the risk of cancer death

A new report by American Cancer Society scientists says new data showing aspirin's potential role in reducing the risk of cancer death bring us considerably closer to the time when cancer prevention can be included in clinical guidelines for the use of aspirin in preventive care. The report, published early online in Nature Reviews Clinical Oncology (April, 2012), says even a 10% reduction in overall cancer incidence beginning during the first 10 years of treatment could tip the balance of benefits and risks favorably in average-risk populations.

Current guidelines for the use of aspirin in disease prevention consider only its cardiovascular benefits, weighed against the potential harm from aspirin-induced bleeding. While daily aspirin use has also been convincingly shown to reduce the risk of colorectal cancer and recurrence of adenomatous polyps, these benefits alone do not outweigh harms from aspirin-induced bleeding in average-risk populations.

But recently published secondary analyses of cardiovascular trials have provided the first randomized evidence that daily aspirin use may also reduce the incidence of all cancers combined, even at low doses (75-100 mg daily).

The current review, led by Michael J. Thun, M.D., vice president emeritus of epidemiology and surveillance research for the American Cancer Society was not designed as a comprehensive review of the literature, but instead is a focused discussion of the key outstanding issues in using aspirin as a cancer prevention tool.

The report says recently published meta-analyses of results from randomized trials of daily aspirin treatment to prevent vascular events have provided provocative evidence that daily aspirin at doses of 75 mg and above might lower both overall cancer incidence and overall cancer mortality.

In six primary prevention trials of daily low-dose aspirin, randomization to aspirin treatment was associated with an approximately 20% reduction in overall cancer incidence between 3 and 5 years after initiation of the intervention (metaodds ratio [OR] = 0.81; 95% CI 0.67-0.98) and a 30% reduction during follow up more than 5 years after randomization (meta-OR = 0.70; 95% CI 0.56-0.88). Cancer mortality was also reduced during study follow up that happened more than 5 years after the start of aspirin use (meta-OR = 0.63; 95% CI 0.49-0.82) in analyses that included 34 trials of daily aspirin at various doses. Surprisingly, the size of the observed benefit did not increase with daily doses of aspirin above 75-100 mg.

Notably, these meta-analyses excluded results from the Women's Health Study (WHS), a large 10-year-long trial of 100 mg of aspirin taken every other day, which reported no reduction in cancer incidence or mortality.

"The accumulating data from randomized clinical trials provide an exciting opportunity to reconsider the potential role of aspirin in cancer prevention," write the authors. They say several important questions remain unanswered, such as the exact magnitude of the overall cancer benefit and which individual cancer sites contribute to this benefit. "However, these new data bring us considerably closer to the time when cancer prevention can be integrated into the clinical guidelines for prophylactic treatment following regulatory review by the FDA and the European Medicines Agency."

Regular aspirin intake halves cancer risk

Scientists have discovered that taking regular aspirin halves the risk of developing hereditary cancers.

Hereditary cancers are those which develop as a result of a gene fault inherited from a parent. Bowel and womb cancers are the most common forms of hereditary cancers. Fifty thousand people in the UK are diagnosed with bowel and womb cancers every year; 10 per cent of these cancers are thought to be hereditary.

The decade-long study, which involved scientists and clinicians from 43 centres in 16 countries and was funded by Cancer Research UK, followed nearly 1,000 patients, in some cases for over 10 years. The study found that those who had been taking a regular dose of aspirin had 50 per cent fewer incidences of hereditary cancer compared with those who were not taking aspirin. The research was published in the Lancet Online on Oct. 28 2011.

The research focused on people with Lynch syndrome which is an inherited genetic disorder that causes cancer by affecting genes responsible for detecting and repairing damage in the DNA. Around 50 per cent of those with Lynch syndrome develop cancer, mainly in the bowel and womb. The study looked at all cancers related to the syndrome, and found that almost 30 per cent of the patients not taking aspirin had developed a cancer compared to around 15 per cent of those taking the aspirin.

Those who had taken aspirin still developed the same number of polyps, which are thought to be precursors of cancer, as those who did not take aspirin but they did not go on to develop cancer. It suggests that aspirin could possibly be causing these cells to destruct before they turn cancerous.

Over 1,000 people were diagnosed with bowel cancer in Northern Ireland last year; 400 of these died from the disease. Ten per cent of bowel cancer cases are hereditary and by taking aspirin regularly the number of those dying from the hereditary form of the disease could be halved.

Professor Patrick Morrison from Queen's University in Belfast, who led the Northern Ireland part of the study, said: "The results of this study, which has been ongoing for over a decade, proves that the regular intake of aspirin over a prolonged period halves the risk of developing hereditary cancers. The effects of aspirin in the first five years of the study were not clear but in those who took aspirin for between five and ten years the results were very clear."

"This is a huge breakthrough in terms of cancer prevention. For those who have a history of hereditary cancers in their family, like bowel and womb cancers, this will be welcome news. Not only does it show we can reduce cancer rates and ultimately deaths, it opens up other avenues for further cancer prevention research. We aim now to go forward with another trial to assess the most effective dosage of aspirin for hereditary cancer prevention and to look at the use of aspirin in the general population as a way of reducing the risk of bowel cancer.

Daily Aspirin at Low Doses Reduces Cancer Deaths

A daily low dose of aspirin significantly reduces the number of deaths from a whole range of common cancers, an Oxford University study has found.

The 20% drop in all cancer deaths seen in the study adds new evidence to the debate about whether otherwise healthy people in their 40s and 50s should consider taking a low dose of aspirin each day.

Aspirin is already known to be beneficial for those at high risk of heart disease. But among healthy people, the benefit in lower chances of heart problems only marginally outweighs the small risk of stomach bleeds.

The large size of the effect now seen in preventing cancer deaths may begin to tip the balance in favour of taking aspirin, the scientists suggest, but say that it is a matter for the health bodies who write treatment guidelines.

"These results do not mean that all adults should immediately start taking aspirin," cautions Professor Peter Rothwell of the Department of Clinical Neurology at Oxford University, who led the work. "But they do demonstrate major new benefits that have not previously been factored into guideline recommendations."

"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 this balance for many people."

However, he adds: "I don't think it's necessarily right for the person who did the research to say what guidelines should be. We can't say with absolute certainty that there won't be some unknown harm in taking aspirin for 30 years, but it looks as if there would be pretty large benefits in reducing cancer deaths. People have to accept there's some uncertainty here."

Professor Rothwell and colleagues recently established that a low dose of aspirin (75 mg per day, or a quarter of the normal dose taken for pain relief) taken for longer than five years reduces death rates from bowel cancer by more than a third.

In this new work, scientists from Oxford, Edinburgh, London and Japan used data on over 670 deaths from cancer in a range of randomised trials involving over 25,000 people. These trials compared daily use of aspirin against no aspirin and were done originally to look for any preventative effect against heart disease.

The results, published in the Lancet, showed that aspirin reduced death due to any cancer by around 20% during the trials. But the benefits of aspirin only became apparent after taking the drug for 5 years or more, suggesting aspirin works by slowing or preventing the early stages of the disease so that the effect is only seen much later.

After 5 years of taking aspirin, the data from patients in the trials showed that death rates were 34% less for all cancers and as much as 54% less for gastrointestinal cancers, such as oesophagus, stomach, bowel, pancreas and liver cancers.

The researchers also wanted to determine if the benefits from aspirin continued over time. By using cancer registries and death records, they were able to follow up what had happened to participants in three of the trials.

They showed that risk of cancer death over a period of 20 years remained 20% lower for all solid cancers among those who had taken aspirin (even though they would have been unlikely to have continued taking aspirin after the trials finished), and 35% lower for gastrointestinal cancers.

It took about 5 years to see a benefit in taking aspirin for oesophagus, pancreatic, brain, and lung cancer; about 10 years for stomach and bowel cancer; and about 15 years for prostate cancer. The 20-year risk of death was reduced by about 10% for prostate cancer, 30% for lung cancer, 40% for bowel cancer and 60% for oesophagus cancer.

As the evidence points to a delayed preventive effect against cancer, Professor Rothwell believes that it would be those who started taking aspirin in their late 40s or 50s -- ie before people's risk of cancer starts increasing -- and then continued for 20 to 30 years who might eventually see the most benefit.

Professor Rothwell estimates that in terms of cost-effectiveness, taking low-dose aspirin daily is likely to be much more cost-effective than those interventions already used for preventing cancer, such as screening for breast or prostate cancer.

He does note that more research is necessary to understand more about the effect aspirin has on cancer.

While this study looked at how aspirin affected deaths from cancer, Professor Rothwell and colleagues now aim to look at any protective effect of aspirin on the incidence or progression of cancer. The researchers also point out that more trial data are needed on breast cancer and other cancers that particularly affect women.

 

Aspirin Fights Cancer

A daily dose of adult-strength aspirin may modestly reduce cancer risk in populations with high rates of colorectal, prostate, and breast cancer if taken for at least five years.

The Women's Health Study trial recently reported that long-term use of low-dose aspirin (about 100mg every other day) does not reduce a woman's cancer risk, but it did not examine whether high doses of aspirin have an effect on cancer risk.

Eric Jacobs, Ph.D., of the American Cancer Society in Atlanta, and colleagues looked for associations between long-term daily aspirin use (at least 325mg/day) and cancer incidence in a group of nearly 70,000 men and 76,000 women. Aspirin use was determined by a questionnaire.

During the 12 year follow-up, nearly 18,000 men and women in the study were diagnosed with cancer. The researchers found that daily use of adult-strength aspirin for at least five years was associated with an approximately 15 percent relative reduction in overall cancer risk, though the decrease was not statistically significant in women. Additionally, aspirin use was associated with a 20 percent reduced risk of prostate cancer and a 30 percent reduced risk of colorectal cancer in men and women, compared to people who didn't take aspirin.

There was no effect on risk in other cancers examined—lung cancer, bladder cancer, melanoma, leukemia, non-Hodgkins lymphoma, pancreatic cancer, and kidney cancer.

Aspirin use for less than five years was not associated with decreased cancer risk.

"Our results do not have immediate clinical implications. Confirmation from randomized trials is necessary before a reduction in cancer risk could be considered a benefit of using adult-strength aspirin. Our results indicate that a randomized trial examining the effect of aspirin on cancer incidence would need to be both large and long term, probably lasting a minimum of 10 years. More evidence is needed before any such trial can be justified," the authors write.