Background: Lynch syndrome is an inherited susceptibility to colorectal cancer (CRC) and other cancers caused by a germline mutation in one of the DNA mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2. Personal and lifestyle factors might modify cancer risks for MMR gene mutation carriers.
Aim: In this study, we estimated associations between aspirin and ibuprofen use and risk of CRC for MMR gene mutation carriers.
Methods: We conducted a birth cohort analysis on 1,745 carriers of a pathogenic mutation in one of the MMR genes (633 MLH1, 839 MSH2, 167 MSH6 and 106 PMS2) who were recruited into the Colon Cancer Family Registry (254 from Canada, 957 from Australia and 534 for the United States). During 77,338 person-years of observation, 725 carriers (41%) were diagnosed with CRC. We used weighted Cox proportional hazards regression to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for associations between use of aspirin and/or ibuprofen and the risk of CRC.
Results: A lower risk of CRC was associated with regular use of: aspirin (HR 0.48, 95% CI 0.26-0.87 for 1-10 years use; and 0.45, 95% CI 0.25-0.80 for >10 years use); ibuprofen (HR 0.46, 95% CI 0.25-0.86 for 1-5 years use; and 0.36, 95% CI 0.12-1.05 for >5 years use); and either aspirin or ibuprofen (HR 0.65, 95% CI 0.40-1.05 for 1-10 years use; and 0.43, 95% CI 0.21-0.90 for >10 years use) compared with never users, after adjusting for potential confounding factors.
Conclusions: There is strong protective association of aspirin and ibuprofen use with a reduction in CRC risk for MMR gene mutations carriers. Our results suggest that regular long-term use of aspirin and ibuprofen might be an effective and acceptable way for mutation carriers to reduce their risk of CRC.