The Colorectal Adenoma/Carcinoma Prevention Programme 3 (CaPP3) trial, led by Professor Sir John Burn at Newcastle University and funded by Cancer Research UK, has found that taking a low daily dose of aspirin reduces bowel cancer risk in people with Lynch syndrome.

Higher doses of aspirin have previously been shown to prevent bowel cancer. In the CaPP2 trial, also led by Professor Burn, it was identified that a 600mg daily dose of aspirin for people with Lynch syndrome cut the risk of bowel cancer in half.

The CaPP3 trial highlights that the lower daily dose of 75-100mg works just as well as higher doses in cutting bowel cancer risk in people with Lynch syndrome – a rare genetic condition that substantially increases the risk of cancers, such as bowel, womb, ovarian and prostate.

Professor of Clinical Genetics at Newcastle University and lead investigator of the CaPP3 trial, Professor Sir John Burn, said: “For 30 years, scientists have observed fewer cancers in people who take aspirin.

“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.

“However, only a quarter of people with Lynch syndrome are currently taking aspirin. 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.”

A rare genetic condition that runs in families, NHS England estimate that 1 in 400 people in England have Lynch syndrome (equivalent to around 175,000 people).

Based on the CAPP2 result, the National Institute of Health and Care Excellence (NICE) currently recommends that people with Lynch syndrome consider taking aspirin daily to prevent bowel cancer.

But a survey carried out in 2016 revealed that less than half (46.7%) of GPs were aware that they should recommend aspirin to people with Lynch syndrome and many were worried about the higher dose. The CaPP3 trial shows that aspirin could be prescribed at lower doses and potentially benefit more people.

Scientists leading the research are now in talks with the British National Formulary, the “drugs bible” used by all pharmacists and doctors, to update the advice it gives on aspirin for use as a cancer prevention drug. This would make it much easier for GPs to prescribe aspirin to those patients.

Lynch syndrome is estimated to cause around 3% of bowel cancer cases in the UK every year, many of them in people under the age of 50.

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.

Patients ‘given hope’

Nick James, 46, a furniture maker from Gosforth in Newcastle, was the first to sign up to the CaPP3 trial in 2014.

Nick decided to undergo genetic testing after his mum died from cancer, and other family members were diagnosed with bowel cancer. After he was referred by his GP to the Northern Genetics Service at Newcastle upon Tyne Hospitals NHS Foundation Trust, his results came back showing that he was a carrier for a faulty gene which causes Lynch syndrome.

His roots in the trial run deep. He owns a patch of woodland in Northumberland and grows his own willow trees, from which he crafts beautiful pieces of furniture. Willow bark is a rich source of salicin, which is used to make acetylsalicylic acid, the active ingredient of aspirin.

Nick now has a colonoscopy every two years and continues to take aspirin, but has no other appointments or treatment connected to Lynch syndrome. He hasn’t had cancer. 

He said: “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.

“It was fascinating to hear about how something as small as aspirin could potentially make such a big difference to my future. 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. 

“Before joining CaPP3 I had never really thought about clinical trials before. But now, I am aware of how important they are to me, my family and future generations. Taking three aspirin tablets a day wasn’t hard, but it has helped this study and it could potentially help lots of people in the future.”

‘Transforming cancer prevention’

The CaPP3 trial involved 1,879 people with Lynch syndrome in the UK, three other European countries and Australia who were treated with aspirin over five years.

Participants on the trial were given three different doses of aspirin – 75-100mg, 300mg or 600mg a day – and received regular checks to see how they were doing throughout.

The trial found that those on the lowest aspirin dose did just as well as those on the higher doses, with fewer bowel cancers across all three doses. Aspirin given at lower doses is likely to cause fewer side-effects, including bleeding and stomach ulcers, than at higher doses.

Dr David Crosby, Head of Prevention and Early Detection Research at Cancer Research UK, said: “The holy grail of cancer research is prevention. We’re in a new era where trials like CaPP3 are transforming how we approach cancer prevention.

“It is exciting that aspirin can offer protection from bowel cancer at low doses. 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.

“We now have really good evidence that aspirin can prevent bowel cancer in those at a high risk of the disease. We hope that the regulators will support the case for formal licensing of aspirin as a cancer prevention drug for people with Lynch syndrome.”

Professor Sir John Burn presented results from the CaPP3 trial at the Cancer Research UK International Cancer Prevention Conference in London.