Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/93080
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dc.contributor.authorAit Ouakrim, D.en
dc.contributor.authorDashti, S.en
dc.contributor.authorChau, R.en
dc.contributor.authorBuchanan, D.en
dc.contributor.authorClendenning, M.en
dc.contributor.authorRosty, C.en
dc.contributor.authorWinship, I.en
dc.contributor.authorYoung, J.en
dc.contributor.authorGiles, G.en
dc.contributor.authorLeggett, B.en
dc.contributor.authorMacrae, F.en
dc.contributor.authorAhnen, D.en
dc.contributor.authorCasey, G.en
dc.contributor.authorGallinger, S.en
dc.contributor.authorHaile, R.en
dc.contributor.authorLe Marchand, L.en
dc.contributor.authorThibodeau, S.en
dc.contributor.authorLindor, N.en
dc.contributor.authorNewcomb, P.en
dc.contributor.authorPotter, J.en
dc.contributor.authoret al.en
dc.date.issued2015en
dc.identifier.citationJournal of the National Cancer Institute, 2015; 107(9):1-11en
dc.identifier.issn0027-8874en
dc.identifier.issn1460-2105en
dc.identifier.urihttp://hdl.handle.net/2440/93080-
dc.description.abstractBackground: 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.en
dc.description.statementofresponsibilityDriss 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 Winen
dc.language.isoenen
dc.publisherOxford University Pressen
dc.rights© The Author 2015.en
dc.subjectHumans; 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; Bias (Epidemiology); Confounding Factors (Epidemiology); 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 PMS2en
dc.titleAspirin, ibuprofen, and the risk of colorectal cancer in Lynch Syndromeen
dc.typeJournal articleen
dc.identifier.rmid0030031217en
dc.identifier.doi10.1093/jnci/djv170en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1074383en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1042021en
dc.identifier.pubid192285-
pubs.library.collectionMedicine publicationsen
pubs.library.teamDS12en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidYoung, J. [0000-0002-1514-1522]en
Appears in Collections:Medicine publications

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