Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome

Driss Ait Ouakrim, Seyedeh Ghazaleh Dashti, Rowena Chau, Daniel D. Buchanan, Mark Clendenning, Christophe Rosty, Ingrid M. Winship, Joanne P. Young, Graham G. Giles, Barbara Leggett, Finlay A. Macrae, Dennis J. Ahnen, Graham Casey, Steven Gallinger, Robert W. Haile, Loïc Le Marchand, Stephen N. Thibodeau, Noralane M. Lindor, Polly A. Newcomb, John D. Potter, John A. Baron, John L. Hopper, Mark A. Jenkins, Aung Ko Win

Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 causes a high risk of colorectal and other cancers (Lynch Syndrome). Use of aspirin has been shown to be associated with a reduced risk of colorectal cancer for the general population as well as for MMR gene mutation carriers. The aim of this study was to determine whether use of aspirin and ibuprofen in a nontrial setting is associated with the risk of colorectal cancer risk for MMR gene mutation carriers. We included 1858 participants in the Colon Cancer Family Registry who had been found to have a pathogenic germline mutation in a MMR gene (carriers). We used weighted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. A total of 714 carriers (38%) were diagnosed with colorectal cancer at a mean age of 42.4 (standard deviation 10.6) years. A reduced risk of colorectal cancer was associated with aspirin use (for 1 month to 4.9 years: HR = 0.49, 95% CI = 0.27 to 0.90, P = .02; for ≥5 years: HR = 0.25, 95% CI = 0.10 to 0.62, P = .003) and ibuprofen use (for 1 month to 4.9 years: HR = 0.38, 95% CI = 0.18 to 0.79, P = .009; for ≥5 years: HR = 0.26, 95% CI = 0.10 to 0.69, P = .007), compared with less than one month of use. Our results provide additional evidence that, for MMR gene mutation carriers, use of aspirin and ibuprofen might be effective in reducing their high risk of colorectal cancer.