Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/93080
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Type: Journal article
Title: Aspirin, ibuprofen, and the risk of colorectal cancer in Lynch Syndrome
Author: Ait Ouakrim, D.
Dashti, S.
Chau, R.
Buchanan, D.
Clendenning, M.
Rosty, C.
Winship, I.
Young, J.
Giles, G.
Leggett, B.
Macrae, F.
Ahnen, D.
Casey, G.
Gallinger, S.
Haile, R.
Le Marchand, L.
Thibodeau, S.
Lindor, N.
Newcomb, P.
Potter, J.
et al.
Citation: Journal of the National Cancer Institute, 2015; 107(9):1-11
Publisher: Oxford University Press
Issue Date: 2015
ISSN: 0027-8874
1460-2105
Statement of
Responsibility: 
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 and Aung Ko Win
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.
Keywords: Humans
Colorectal Neoplasms
Colorectal Neoplasms, Hereditary Nonpolyposis
Aspirin
Ibuprofen
DNA Repair Enzymes
Adaptor Proteins, Signal Transducing
DNA-Binding Proteins
Nuclear Proteins
Anti-Inflammatory Agents, Non-Steroidal
Anticarcinogenic Agents
Registries
Prevalence
Proportional Hazards Models
Heterozygote
Germ-Line Mutation
Adult
Aged
Middle Aged
United States
Female
Male
MutS Homolog 2 Protein
Adenosine Triphosphatases
DNA Mismatch Repair
MutL Protein Homolog 1
Mismatch Repair Endonuclease PMS2
Bias
Confounding Factors, Epidemiologic
Rights: © The Author 2015.
DOI: 10.1093/jnci/djv170
Grant ID: http://purl.org/au-research/grants/nhmrc/1074383
http://purl.org/au-research/grants/nhmrc/1042021
Published version: http://dx.doi.org/10.1093/jnci/djv170
Appears in Collections:Aurora harvest 2
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