The international trial - known as CAPP2 - involved patients with Lynch syndrome from around the world and revealed that two aspirins a day, for an average of two-and-a-half years, reduced the rate of bowel cancer by half.
The study, led by experts at the Universities of Newcastle and Leeds in the UK, published in the journal The Lancet, is a planned double-blind 10-year follow-up, supplemented in more than half of recruits with comprehensive national cancer registry data for up to 20 years.
"I had an idea 30 years ago that people with a genetic predisposition to colon cancer could help us to test whether aspirin really could reduce the risk of cancer," said study researcher Sir John Burn from Newcastle University.
"Patients with Lynch syndrome are high risk and this offered statistical power to use cancer as an endpoint - they are like the canaries in the mine who warned the miners that there was gas," Burn added.
The study further strengthens the National Institute for Health and Care Excellence (NICE) recommendation on taking daily aspirin for those at high risk and supports wider use of aspirin to prevent cancer.
Based on the preliminary five-year data from the CAPP2 trial, NICE recommended that aspirin should be offered for the prevention of bowel cancer in adults with Lynch syndrome.
According to the researchers, it took a long time to start the trial and to recruit enough people in 16 countries, but this study has finally given us an answer.
The study involved 861 patients with Lynch syndrome, which affects about one in 200 people in the population. These people have a genetic problem with DNA repair, making them at much higher risk of cancers like thsoe of bowel and womb.
A group of 427 patients were randomised to aspirin continuously for two years and 434 were allocated to placebo group and then they were all followed for 10 years.
Out of those given two aspirins each day (600mg) there were 18 fewer colon cancers, representing a drop of 42.6 per cent.
When all 163 Lynch syndrome cancers are included in the analysis - such as cancer of the endometrium or womb - there was an overall reduced risk of cancer of 24 per cent in those taking aspirin or 37 per cent in those who took aspirin for the full two years.
"Two aspirins a day for a couple of years gives protection that lasts more than 10 years," Burn said.
"For people at high cancer risk, the benefits are clear - aspirin works. Our new international trial, CaPP3, will see if smaller doses work just as well," Burn added.