Effect of Chemoprevention by Low-dose Aspirin of New or Recurrent Colorectal Adenomas in Patients With Lynch Syndrome

Lynch syndrome (LS) is the most common inherited colorectal cancer syndrome, and results from germline mutations in mismatch repair genes that confer a high lifetime risk of colorectal cancer (CRC) (60 to 70%). Most CRCs arise from asymptomatic polyps. Development of such polyps into cancer can be prevented if polyps are detected early by endoscopy and removed. Colonoscopy is proposed every 2 years in LS patients more than 25 years old, and every year when colonic neoplasia has been detected. Efficient chemoprevention has the potential to represent a cost-effective intervention in these patients and could allow a delay in colonoscopic surveillance.

Several epidemiological studies have shown that regular use of low dose aspirin (75 to 300 mg/d) is associated with a 20 to 30 % reduction in the risk of sporadic colonic polyps and CRC. Four randomised controlled trials (RCT) have also shown a decrease in colorectal polyp recurrence. In a pooled analysis of cardio-vascular prevention RCTs, as well as in a meta-analysis, daily aspirin was associated with a reduced risk of CRC and CRC associated mortality. Aspirin preventive benefit is expected to outweigh its putative side effects in high risk patients. The CAPP2 study in Lynch syndrome patients showed that aspirin (300 mg x2/d) did not reduce significantly the risk of colorectal neoplasia after 29 months, but an extended follow-up (mean 56 months) showed a reduction in colorectal cancer in the aspirin group. In this study, the endoscopic follow-up was not optimal with a relatively low detection rate of colorectal neoplasia according to usual reported rate when chromo-endoscopy is performed. So, the real effect and clinical benefit of aspirin are still to be characterised in Lynch syndrome patients.

Inclusion criteria

• Patient with Lynch syndrome bearing an alteration of "mismatch repair" genes or,when no characteristic alteration has been found, with a personal or family history of Lynch syndrome according to modified Amsterdam criteria
• Aged more than 25 years, et aged more than 18 years with an early familial history and any reason to perform a colonoscopy every 2 years
• Aged less than 75 years

Exclusion criteria

• Known allergy to aspirin (including a history of asthma induced by the administration of salicylates or substances with similar activity, including non-steroidal anti-inflammatory)
• Need for a prolonged treatment (prevention of cardio-vascular risk) or repeated treatments (recurring migraines) using aspirin or another non-steroidal anti-inflammatory drug (NSAID)
• Pregnancy or breast feeding
• Participation to another clinical trial during the 12 weeks before inclusion