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

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 Morey Lindor, Polly A. Newcomb, John D. PotterJohn A. Baron, John L. Hopper, Mark A. Jenkins, Aung Ko Win

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
JournalJournal of the National Cancer Institute
Volume107
Issue number9
DOIs
StatePublished - Sep 1 2015

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Hereditary Nonpolyposis Colorectal Neoplasms
Ibuprofen
DNA Mismatch Repair
Aspirin
Colorectal Neoplasms
Confidence Intervals
Germ-Line Mutation
Genes
Mutation
Colonic Neoplasms
Registries
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ouakrim, D. A., Dashti, S. G., Chau, R., Buchanan, D. D., Clendenning, M., Rosty, C., ... Win, A. K. (2015). Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome. Journal of the National Cancer Institute, 107(9). https://doi.org/10.1093/jnci/djv170

Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome. / Ouakrim, Driss Ait; Dashti, Seyedeh Ghazaleh; Chau, Rowena; Buchanan, Daniel D.; Clendenning, Mark; Rosty, Christophe; Winship, Ingrid M.; Young, Joanne P.; Giles, Graham G.; Leggett, Barbara; Macrae, Finlay A.; Ahnen, Dennis J.; Casey, Graham; Gallinger, Steven; Haile, Robert W.; Le Marchand, Loïc; Thibodeau, Stephen N; Lindor, Noralane Morey; Newcomb, Polly A.; Potter, John D.; Baron, John A.; Hopper, John L.; Jenkins, Mark A.; Win, Aung Ko.

In: Journal of the National Cancer Institute, Vol. 107, No. 9, 01.09.2015.

Research output: Contribution to journalArticle

Ouakrim, DA, Dashti, SG, Chau, R, Buchanan, DD, Clendenning, M, Rosty, C, Winship, IM, Young, JP, Giles, GG, Leggett, B, Macrae, FA, Ahnen, DJ, Casey, G, Gallinger, S, Haile, RW, Le Marchand, L, Thibodeau, SN, Lindor, NM, Newcomb, PA, Potter, JD, Baron, JA, Hopper, JL, Jenkins, MA & Win, AK 2015, 'Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome', Journal of the National Cancer Institute, vol. 107, no. 9. https://doi.org/10.1093/jnci/djv170
Ouakrim, Driss Ait ; Dashti, Seyedeh Ghazaleh ; Chau, Rowena ; Buchanan, Daniel D. ; Clendenning, Mark ; Rosty, Christophe ; Winship, Ingrid M. ; Young, Joanne P. ; Giles, Graham G. ; Leggett, Barbara ; Macrae, Finlay A. ; Ahnen, Dennis J. ; Casey, Graham ; Gallinger, Steven ; Haile, Robert W. ; Le Marchand, Loïc ; Thibodeau, Stephen N ; Lindor, Noralane Morey ; Newcomb, Polly A. ; Potter, John D. ; Baron, John A. ; Hopper, John L. ; Jenkins, Mark A. ; Win, Aung Ko. / Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome. In: Journal of the National Cancer Institute. 2015 ; Vol. 107, No. 9.
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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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T1 - Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome

AU - Ouakrim, Driss Ait

AU - Dashti, Seyedeh Ghazaleh

AU - Chau, Rowena

AU - Buchanan, Daniel D.

AU - Clendenning, Mark

AU - Rosty, Christophe

AU - Winship, Ingrid M.

AU - Young, Joanne P.

AU - Giles, Graham G.

AU - Leggett, Barbara

AU - Macrae, Finlay A.

AU - Ahnen, Dennis J.

AU - Casey, Graham

AU - Gallinger, Steven

AU - Haile, Robert W.

AU - Le Marchand, Loïc

AU - Thibodeau, Stephen N

AU - Lindor, Noralane Morey

AU - Newcomb, Polly A.

AU - Potter, John D.

AU - Baron, John A.

AU - Hopper, John L.

AU - Jenkins, Mark A.

AU - Win, Aung Ko

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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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