Low-dose aspirin: effective cancer chemoprevention in Lynch syndrome
Mené sur 1 879 patients atteints du syndrome de Lynch (durée médiane de suivi : 66,4 mois), cet essai randomisé international évalue la non-infériorité, du point de vue de l'incidence des cancers liés au syndrome, de faibles doses quotidiennes d'aspirine (100 mg ou 300 mg) par rapport à une dose plus forte (600 mg)
Lynch syndrome is a common inherited cancer susceptibility syndrome defined by pathogenic variants in the DNA mismatch repair genes MLH1, MSH2, MSH6, and PMS2, and deletions in EPCAM, which might result in altered expression of MSH2. Colorectal cancer is the most commonly occurring cancer in people with Lynch syndrome, but there is an increased risk of a range of cancers including endometrial and upper gastrointestinal cancers, with a lifetime cancer risk of up to 80%.
The CAPP2 randomised controlled trial showed that 600 mg aspirin when compared with placebo reduced the long-term risk of cancer by around half in people with Lynch syndrome.1 Before CAPP2, observational data from trials of prevention of cardiovascular events indicated that aspirin doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer.2
In The Lancet Gastroenterology & Hepatology, John Burn and colleagues3 report the outcomes of the CaPP3 trial, in which 1879 Lynch syndrome carriers were randomly assigned to receive either 100 mg, 300 mg, or 600 mg aspirin daily for up to 5 years. 216 Lynch syndrome cancers were diagnosed after a median of 66·4 months (IQR 32·1–84·0). In the intention-to-treat population, the study demonstrated the non-inferiority of low-dose (100 mg daily) aspirin compared with high-dose aspirin in the prevention of Lynch syndrome-related cancers. Given the efficacy lag period of 5–7 years after aspirin is commenced,1,2 longer follow-up might be needed to confirm these findings.
The Lancet Gastroenterology & Hepatology , commentaire en libre accès, 2026