Scope of the Problem
Colorectal cancer (CRC) is preventable by removing pre-cancerous lesions or adenomatous polyps long before invasive cancer develops. The two most common inherited syndromes are familial adenomatous polyposis syndrome (FAP) and hereditary non-polyposis colon cancer (HNPCC) or Lynch syndrome. HNPCC accounts for 3 to 5% of all colorectal cancers and FAP accounts for 1% of cancers of the colon and rectum (ACS, 2011). For patients with a genetic predisposition for CRC, cancer can develop at an earlier age than in the general population. The Colorectal Adenoma/Carcinoma Prevention Programme (CAPP) conducted a chemoprevention trial specifically focused on persons with HNPCC. The trial was aimed at investigating the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch Syndrome. Recently, Burn and colleagues (2011) published the long term follow-up of participants randomly assigned to aspirin or placebo.
- Carriers of Lynch Syndrome (n=861) were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo for up to 4 years
- Participants and investigators were masked to treatment allocation (double blind)
- The study had a pre-planned design for 10 years’ follow-up
- The primary outcome was development of colorectal cancer
- At a mean follow-up of 55.7 months, 48 participants developed 53 primary colorectal cancers (18 of 427 assigned to aspirin and 30 of 434 assigned to aspirin placebo)
- There were 10 participants in each arm (aspirin vs. aspirin placebo)who developed CRC within 2 years of randomization
- Eight participants randomized to the aspirin arm and 20 participants randomized to the aspirin placebo arm had their first CRC more than 2 years from randomization
- Five of the participants who developed CRC had 2 primary colon cancers
- Intention-to-treat analysis of time to first CRC showed a hazard ratio (HR) of 0.63 (95% CI 0.35 -1.13, p = 0.12)
- Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0.56 (95% CI 0.32 – 0.99, p = 0.05)
- Participants completing 2 years of intervention, per protocol analysis yielded an HR of 0.41 (0.19 – 0.86, p = 0.02) and an IRR of 0.37 (0.18 – 0.78, p = 0.008)
The authors concluded that 600 mg of aspirin daily for a mean of 25 months substantially reduced the incidence of CRC in carriers of Lynch Syndrome.
In CRC, there have been observational studies that have supported the use of aspirin and NSAIDs in reduction of colorectal adenoma risk and carcinoma. There have been four randomized controlled trials supporting use of aspirin for reduction of colorectal adenoma risk in average and high-risk populations.
Burns and colleagues (2011) focused their trial on a specific group of genetically at risk persons for developing CRC and identified a benefit of daily aspirin at a dose of 600 mg in reducing the incidence of CRC in carriers of Lynch Syndrome. They were the first to use prevention of CRC as a primary endpoint. . The door has been opened for further exploration of chemoprevention with aspirin in persons with Lynch Syndrome. What remains the unknown answer for the average- and high-risk person for developing CRC is the optimal dose and duration of aspirin in chemoprevention
American Cancer Society. Colorectal cancer: early detection. Retrieved from http://www.cancer.org/docroot/CRI/content/CRI_2_6X_Colorectal_Cancer_Early_Detection_10.asp?sitearea=&level=
Burns, J., Gerdes, A.M., Macrae, F., Mecklin, J.P., Moeslein, G., Olschwang, S.,… Bishop, D.T. (2011). Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: An analysis from the CAPP2 randomised controlled trial. The Lancet, Published online October 28. doi:10.1016/S0140-6736(11)61049-0 Link to abstract: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961049-0/fulltext#article_upsell