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

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

1. Driss Ait Ouakrim, 
2. Seyedeh Ghazaleh Dashti, 
3. Rowena Chau, 
4. Daniel D. Buchanan,
5. Mark Clendenning, 
6. Christophe Rosty, 
7. Ingrid M. Winship, 
8. Joanne P. Young, 
9. Graham G. Giles,
10. Barbara Leggett, 
11. Finlay A. Macrae, 
12. Dennis J. Ahnen, 
13. Graham Casey, 
14. Steven Gallinger,
15. Robert W. Haile, 
16. Loïc Le Marchand, 
17. Stephen N. Thibodeau, 
18. Noralane M. Lindor,
19. Polly A. Newcomb, 
20. John D. Potter, 
21. John A. Baron, 
22. John L. Hopper, 
23. Mark A. Jenkins and
24. Aung Ko Win

+Author Affiliations

1. Affiliations of authors: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY);School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (PAN, JDP); School of Public Health, University of Washington, Seattle, WA (PAN, JDP); Centre for Public Health Research, Massey University, Wellington, New Zealand (JDP); Department of Medicine, University of North Carolina, Chapel Hill, NC (JAB); Department of Epidemiology and Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea (JLH).

1. Correspondence to: Aung Ko Win, PhD, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Level 3, 207 Bouverie Street, The University of Melbourne, VIC 3010 Australia (e-mail: awin@unimelb.edu.au).

• Received August 27, 2014.
• Revision received February 9, 2015.
• Accepted May 22, 2015.

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.

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