Abstract
Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC) and confers a high lifetime risk of CRC estimated to be up to 60%. Colonoscopy is recommended every 2 years in LS patients above the 20–25-year-old age bracket, and every year when colonic neoplasia has been detected. Efficient chemoprevention has the potential to represent a cost-effective intervention in these high-risk patients and could allow a delay in colonoscopy surveillance. Several epidemiological studies have shown that regular use of low dose aspirin is associated with a 20 to 30% reduction in the risk of sporadic colonic adenomas and colorectal cancer regardless of family risk. However, in recent large randomized trials in specific populations, aspirin use showed no protection for colorectal cancer. A prospective randomized CAPP-2 trial evaluated the effect of aspirin use in LS patients. The primary analysis of this trial showed no significant decrease in CRC in LS patients under daily aspirin. However, a preplanned secondary analysis after an extended follow-up showed a significant reduced risk of CRC in the aspirin group in the per-protocol analysis. The real effect and clinical benefit of aspirin are still to be consolidated in this population. The AAS-Lynch trial—a prospective, multicentric, double-blind, placebo-controlled, randomized clinical trial—was designed to investigate if daily aspirin therapy, at a dose of 100 or 300 mg, would decrease the occurrence or recurrence of colorectal adenomas in patients under 75 years of age, compared with placebo.Trial registrationClinicalTrials.gov NCT02813824. Registered on 27 June 2016. The trial was prospectively registered.
Highlights
Lynch syndrome is the most common cause of inherited colorectal cancer
Eligibility criteria Eligible subjects are adults aged 18 to 75 years with Lynch syndrome (LS) carrying a defined “mismatch repair” gene mutation or, when no characteristic alteration had been found, with a personal or family history of LS according to modified Amsterdam criteria (CRC diagnosed before 50 years of age; presence of synchronous or metachronous colorectal or other LS-related tumors regardless of age; colorectal cancer (CRC) with MSI-high histology diagnosed in a patient who is younger than 60 years of age; CRC diagnosed in a patient with one or more first-degree relatives with a LS-related cancer which was diagnosed under 50 years of age; and CRC diagnosed in a patient with two or more first- or second-degree relatives with LS-related cancer regardless of age)
The initial hypothesis was constructed with a 30% adenoma prevalence in the placebo group and a reduction of 28% expected in the aspirin group, based on our previous randomized controlled trials (RCT) on patients without Lynch syndrome but with a history of colorectal adenomas [8]
Summary
Lynch syndrome is the most common cause of inherited colorectal cancer. It is linked to germline alterations in mismatch repair genes that confer a high lifetime risk of colorectal cancer estimated to be as high as 60%. We designed the AAS-Lynch trial, which is a prospective, multicentric, double-blind, placebo-controlled, randomized clinical trial, to investigate whether the daily use of aspirin, at a dose of 100 or 300 mg, in LS patients under 75 years of age, would decrease the occurrence or recurrence of colorectal adenomas, compared with placebo. This trial will investigate the role of the gut microbiota in adenoma apparition or recurrence in LS patients
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