Low-dose aspirin can prevent bowel cancer in people with Lynch syndrome

This entry is part 4 of 5 in the series Stand Up To Cancer

Aspirin, one of the oldest and most common medicines in the world, has roots that stretch deep into ancient history. Its key ingredient was first developed from willow bark, which has been used for its healing properties for thousands of years.

But it’s only recently that we’ve begun to uncover one of aspirin’s biggest benefits. Over the past few decades, scientists have found that the simple home painkiller can help prevent bowel cancer in high-risk groups.

And now, thanks to our Stand Up To Cancer-funded CaPP3 trial, we know the best dose of aspirin for the job.

CaPP3’s results show that taking as little as 75 to 100mg of aspirin each day can halve the risk of bowel cancer in people with Lynch syndrome, a heritable genetic condition that makes bowel cancer much more likely.

The findings mean regulators and doctors should soon be able to recommend a specific low-dose aspirin prescription for people with Lynch syndrome, protecting many more of them from bowel cancer.

A little dose goes a long way

CaPP3, as its name suggests, is the third trial in the Colorectal Adenoma/Carcinoma Prevention Programme.

With our funding, CaPP2 first showed that a 600mg daily dose of aspirin could halve the risk of bowel cancers linked to Lynch syndrome. However, that study wasn’t designed to find the best dose of the drug, and 600mg is much larger than the doses used to manage other long-term conditions. That means it comes with a higher risk of side-effects, which, in some rare cases, can include bleeding in the stomach.

As a result, although the National Institute of Health and Care Excellence (NICE) now recommends that people with Lynch syndrome should consider taking daily aspirin, it hasn’t been able to instruct doctors to prescribe a specific dose.

A survey conducted in 2016 also revealed that less than half of GPs in the UK (46.7%) knew that daily aspirin could help protect Lynch syndrome carriers from bowel cancer.

That’s what makes CaPP3 so crucial. It was set up to identify the optimal aspirin dose for preventing cancer while minimising the risk of side effects – the missing information needed to change regulations and help GPs understand how to use the drug to lower people’s bowel cancer risk.

So, over the course of five years, CaPP3 gave 1,879 people with Lynch syndrome varying daily doses of aspirin, either 100mg (falling to 75mg after two years), 300mg or 600mg.

The results have now shown that those on the lowest dose of aspirin were just as unlikely to get cancer as those taking higher doses.

“For 30 years, scientists have observed fewer cancers in people who take aspirin,” says Sir John Burn, Professor of Clinical Genetics at Newcastle University, who led the research. “The CaPP3 trial now tells us that aspirin can prevent bowel cancer at lower doses, minimising the chances of side-effects whilst offering vital protection for people with Lynch syndrome.”

Armed with the results of the trial, Burn and his team are now pushing for low-dose aspirin to be included in the British National Formulary, the “drugs bible” used by doctors and pharmacists across the country, as a way of preventing cancer in people with Lynch syndrome.

“Only a quarter of people with Lynch syndrome are currently taking aspirin,” Burn says. “Too many people are missing out on a potentially life-changing opportunity to prevent cancer.  

“We’re now engaging with the regulators to change prescribing guidelines so that aspirin can be used more widely for people with a high risk of bowel cancer. We have a chance to give more people with Lynch syndrome protection which would reduce their fear of bowel cancer in the future.”

Nick’s story

Nick James, a 46-year-old furniture maker from Gosforth, Newcastle, is one of the people benefitting from aspirin thanks to CaPP3.

Nick James outside leaning against a tree. — Nick James

Nick went for genetic testing to understand his cancer risk after losing his mum to cancer. Many of his family members had also been diagnosed with the disease. Looking back at his family tree, he realised that there seemed to be a pattern. That was confirmed by the test results, which showed he had Lynch syndrome.

As soon as he was able, Nick became the first person to sign up for CaPP3 in 2014. He remained well throughout the trial and is still taking daily aspirin today. He also goes for a screening colonoscopy every two years.

“Finding out I had a faulty gene that causes Lynch syndrome was extremely daunting, but taking part in this trial has given me hope that there is something that can reduce the chances of me and others developing cancer,” says Nick.

And, uniquely, as Nick goes to work every morning, he’s reminded of where that hope started.

Nick makes his furniture from willow trees, which he grows in a small patch of woodland in Northumberland. Serendipitously, his craft and his treatment are rooted in the same tree.

“It was fascinating to hear about how something as small as aspirin could potentially make such a big difference to my future,” Nick says. “I was first through the door with the trial – no hesitation. It’s full circle that I work with trees, and my treatment derives from the willow tree, where the natural form of aspirin comes from.”

Lynch syndrome, Lynch choices and preventing bowel cancer

Lynch syndrome affects how the most foundational part of our body, our DNA, repairs itself. In some cells, particularly in the bowel, this can lead to damage building up in the sections of DNA (genes) that control growth, making cancer much more likely.

Over the course of their life, around 70% of men and 50% of women with Lynch syndrome are diagnosed with bowel cancer, compared to 6% of men and 5% of women in the general population. Overall, the condition is estimated to cause around 3% of bowel cancer cases in the UK every year.

“Research shows that up to 1 in 279 people are Lynch syndrome carriers but around 95% aren’t aware of it,” explains Kelly Kohut, an NHS genetic counsellor who worked on our new Lynch Choices website. “Lynch syndrome can significantly increase people’s risk of getting cancers at a young age and there’s a 50% chance of them passing their condition to their children.”

Lynch Choices, which was developed by a team at the University of Southampton, provides information, advice and real-life patient experiences to help people with Lynch syndrome understand their condition and work with their doctors to get the most appropriate care.

“With the NHS England National Transformation Project improving testing for Lynch syndrome and identifying more carriers, we wanted to ensure we had a user-friendly, patient-facing resource that was relevant, meaningful and as engaging as possible,” says Kohut.

The site explains how people can take aspirin or have preventative surgery to lower their risk of Lynch-syndrome linked bowel cancers. It also includes information on going for bowel screening from age 25, cancer symptoms, and diet and lifestyle.

“My research showed that there were gaps in information leaving people feeling unsupported in their decision making,” explains Kohut, who contributed to the site as part of her PhD. “Patients reported asking their GP about aspirin and found that the GP didn’t know about Lynch syndrome. The Lynch Choices website includes a decision aid to help people think about what matters to them when they decide whether or not to take aspirin.”

The results of CaPP3 should make that process much easier – and, with our funding, scientists at the University of Oxford are working on another tool that could be just as valuable. The Lynchvax project is working towards a vaccine that could also help prevent cancers linked to Lynch syndrome.

Dr David Crosby, our head of prevention and early detection research, calls work like this, which has the potential to stop cancer before it even starts, the “holy grail” of cancer research.

“We’re in a new era where trials like CaPP3 are transforming how we approach cancer prevention,” Crosby says. “People with Lynch syndrome get regular colonoscopies and live with the anxiety that they are highly likely to develop bowel cancer in their lifetime. Taking aspirin daily could cut this risk by at least half and alleviate their fears.”