Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, UK
Observational studies show that aspirin reduces colorectal cancer (CRC), especially with prolonged use. In four adenoma prevention randomized controlled trials (RCTs), aspirin at any dose reduced the risk of a colorectal adenoma by an average of 17% and advanced adenomas by 28%. Registry follow-up for a median of 18 years after five RCTs showed that treatment with any aspirin dose reduced the 20-year CRC risk by 24% and the CRC-associated mortality by 35%. A meta-analysis of eight trials with a total of 25,570 patients showed a 21% lower risk of death from any cancer. The trial CAPP1(Concerted Action Polyposis Prevention 1) tested aspirin 600 mg/day and/or resistant starch 30 g/day in 200 adolescent familial adenomatous polyposis carriers. Aspirin treatment resulted in a non-significant reduction in polyp number and a significant reduction in polyp size among patients treated with aspirin for more than 1 year. The CAPP2 RCT used the same interventions in 937 Lynch syndrome (LS) patients, which was the first RCT to have cancer prevention as a primary endpoint. Aspirin did not reduce the risk of colorectal neoplasia in a mean treatment period of 29 months but double-blind post-intervention follow-up has revealed that 48 participants developed 53 CRCs. Protocol analysis showed 60% fewer cancers with aspirin (p = 0.02) apparent from 4 years, with a similar effect on other LS cancers. CAPP3 will involve a double-blind dose inferiority trial comparing 100, 300 or 600 mg daily in 3,000 gene carriers. We can now recommend aspirin in people at high risk of CRC.
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