Aspirin and bowel cancer
It’s almost thirty years since Gabriel Kune in Melbourne published a case control study of people with bowel cancer and reported a difference in the proportion of people using regular anti-inflammatory drugs like aspirin. They concluded that regular use was associated with a much lower cancer risk. Over the next decade several papers using large data sets supported this conclusion. The big question was whether the aspirin prevented cancer or simply led to its earlier discovery. Another possibility was that people who need aspirin are less prone to cancer. The way to resolve this was to set up formal trials.
One approach was to randomly give a very large number of people either an aspirin or a placebo then follow them. The US Women’s Health Study in the USA followed this route. Beginning in the mid 90’s they offered about 18000 women alternate day 81mg cardio aspirin or placebo and gave them a vitamin tablet the other day. In 2005 the study reported no effect of the aspirin on cancer. Several trials focused on polyp prevention. They argued that bowel cancer develops from polyps so preventing them should provide support for cancer prevention. The results were mixed; aspirin reduces polyps only by 15%.
In the late 80’s our team had begun to focus on teenagers with Familial Adenomatous Polyposis (FAP) who develop hundreds of polyps and need preventive surgery. We set up a European trial involving over 200 young people receiving either 2 aspirins or placebo and a sachet of indigestible starch powder compared to normal cornstarch. There was great support from the families but neither treatment had much effect on polyps. Meanwhile, we had been involved in the l search for the cause of Hereditary Non-Polyposis Colon Cancer and by chance, the first patient in whom a mismatch repair gene was shown to be faulty was a Newcastle patient.
By the end of February 1994 we had become the world’s first service to offer genetic tests for what we now call Lynch syndrome. We immediately set about designing a new international study, to be called CAPP2, to test aspirin and resistant starch in a much bigger group of high risk adults. We decided to count polyps first and arrange longer follow up to see if we might also reduce cancers. Our first report in 2008 was also a disappointment. Neither treatment had any obvious effect on polyps. But we pressed on to count cancers and when the first recruits reached their 10 year anniversary we analysed the data.
The overall follow up was an average of 5 years and we published in the Lancet in 2011 a reduction of more than 50% in colon and other cancers. That year, Peter Rothwell and colleagues produced an amazing analysis of the cancer rates in people who had taken part in the early aspirin trials to test the effects in people at risk of strokes and heart attacks. Using cancer registries around Europe they found that people who had been given the active tablets in those trials had fewer cancers. The US Women’s health Study recontacted their population and found that beyond 10 years the rate of bowel cancers dropped by about 20%.
So we are slowly edging to a recommendation that people at increased risk of bowel cancer should take regular aspirin. We are still not sure how much to recommend or whether we should only focus on people at high risk. We have launched CaPP3 to ask people with Lynch syndrome to take aspirin. If they agree, we give them either 2 aspirin tablets a day like in CAPP2, or 1 tablet or a 100mg Cardio aspirin (“baby aspirin”). For the first two years they won’t know which dose they are on so we can collect reliable information about side effects then we prescribe the aspirin for at least another three years and count how many cancers develop. We have over 850 people in the study. If you have Lynch syndrome, please join us! You can follow me on twitter (@capp3), look up www.capp3.org or contact your local genetics centre.
By Professor Sir John Burn, Institute of Genetic Medicine, Newcastle University.