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

Publication Type:

Journal Article

Source:

Journal of the National Cancer Institute, Volume 107, Issue 9 (2015)

Keywords:

Adaptor Proteins, Signal Transducing, Adenosine Triphosphatases, Adult, Aged, Anti-Inflammatory Agents, Non-Steroidal, Anticarcinogenic Agents, Aspirin, Bias (Epidemiology), Colorectal Neoplasms, Colorectal Neoplasms, Hereditary Nonpolyposis, Confounding Factors (Epidemiology), DNA Mismatch Repair, DNA Repair Enzymes, DNA-Binding Proteins, Female, Germ-Line Mutation, Heterozygote, Humans, Ibuprofen, Male, Middle Aged, MutS Homolog 2 Protein, Nuclear Proteins, Prevalence, Proportional Hazards Models, Registries, United States

Abstract:

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.