Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome
Year: 2015
Type: article
Study design: Observational Study
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.
DOI: 10.1093/jnci/djv170
Authors: 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
Institutions: The Royal Melbourne Hospital, The University of Queensland, The University of Melbourne, Queen Elizabeth Hospital, South Australian Health and Medical Research Institute, The University of Adelaide, Cancer Council Victoria, Royal Brisbane and Women's Hospital, University of Colorado Denver, University of Southern California, University of Toronto, Stanford University, University of Hawaiʻi at Mānoa, Mayo Clinic, Mayo Clinic in Arizona, University of Washington, Fred Hutch Cancer Center, Massey University, Seoul National University
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1474361505, USC Consortium:Colorectal Cancer Family Registry, The Colon Cancer Family Registry: USC Consortium, G2201668368, G2324611989, Colon Cancer Family Registry Cohort, The Colon Cancer Family Registry: Hawaii, G322677814, Seattle Colorectal Cancer Family Registry (CFR), G3913695697, Hawaii Colorectal Cancer Family Registry, Ontario Registry for Studies of Familial Colon Cancer, G4539328454, Familial Colorectal Neoplasia Collaborative Group, G520127953, G5269726731, The Colon Cancer Family Registry: Australasia, G5786682175, Bowel cancer prevention, The Colon Cancer Family Registry: Seattle, G6034862151, The Familial Colorectal Neoplasia Collaborative Group, The Colon Cancer Family Registry: Ontario, Precision Public Health for major cancers - novel approaches to building the genetic, epigenetic and lifestyle knowledge base for assessing risk and prognosis, G731770265, G7555119139, G804866679, AUSTRALASIAN COLORECTAL CANCER FAMILY REGISTRY, G9000052799, G9000058811, G9000131717, G9000232507, G980164052
OpenAlex ID: W1949617006