Søren Friis, MD; Anders H. Riis, MSc; Rune Erichsen, MD; John A. Baron, MD; Henrik T. Sørensen, MD, DMSc
This article was published online first at www.annals.org on 25 August 2015.
Grant Support: By the Danish Cancer Society (grant R73-A4284-13-S17) and the Aarhus University Research Foundation.
Disclosures: Dr. Baron reports an issued use patent for colorectal chemopreventive use of aspirin, which is currently unlicensed. Dr. Sørensen reports that the Department of Clinical Epidemiology at Aarhus University Hospital is involved in studies with funding from various companies, none of which have relation to the present study. Authors not named here have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0039.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement:Study protocol: Available from Dr. Friis (e-mail, email@example.com). Statistical code and data set: Available from Mr. Riis (e-mail, firstname.lastname@example.org).
Corresponding Author: Søren Friis, MD, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen Ø, Denmark; e-mail, email@example.com.
Current Author Addresses: Dr. Friis: Danish Cancer Society Research Centre, Strandboulevarden 49, 2100 Copenhagen Ø, Denmark.
Mr. Riis and Drs. Erichsen and Sørensen: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark.
Dr. Baron: University of North Carolina at Chapel Hill, 4105 Bioinformatics Building, CB 7080, Mason Farm Road, Chapel Hill, NC 27599-7080.
Author Contributions: Conception and design: S. Friis, A.H. Riis, R. Erichsen, H.T. Sørensen.
Analysis and interpretation of the data: S. Friis, A.H. Riis, R. Erichsen, J.A. Baron, H.T. Sørensen.
Drafting of the article: S. Friis, A.H. Riis.
Critical revision of the article for important intellectual content: A.H. Riis, R. Erichsen, J.A. Baron, H.T. Sørensen.
Final approval of the article: S. Friis, A.H. Riis, R. Erichsen, J.A. Baron, H.T. Sørensen.
Statistical expertise: A.H. Riis.
Obtaining of funding: H.T. Sørensen.
Administrative, technical, or logistic support: H.T. Sørensen.
Collection and assembly of data: S. Friis, A.H. Riis, H.T. Sørensen.
Friis S, Riis AH, Erichsen R, Baron JA, Sørensen HT. Low-Dose Aspirin or Nonsteroidal Anti-inflammatory Drug Use and Colorectal Cancer Risk: A Population-Based, Case–Control Study. Ann Intern Med. 2015;163:347-355. doi: 10.7326/M15-0039
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Published: Ann Intern Med. 2015;163(5):347-355.
A recent comprehensive review concluded that additional research is needed to determine the optimal use of aspirin for cancer prevention.
To assess associations between the use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) and colorectal cancer risk.
Population-based, case–control study.
Patients with first-time colorectal cancer in northern Denmark between 1994 and 2011. Population control participants were selected by risk set sampling.
Data on drug use, comorbid conditions, and history of colonoscopy were obtained from prescription and patient registries. Use of low-dose aspirin (75 to 150 mg) and nonaspirin NSAIDs was defined according to type, estimated dose, duration, and consistency of use.
Among 10 280 case patients and 102 800 control participants, the adjusted odds ratios (ORs) for colorectal cancer associated with ever use (≥2 prescriptions) of low-dose aspirin and nonaspirin NSAIDs were 1.03 (95% CI, 0.98 to 1.09) and 0.94 (CI, 0.90 to 0.98), respectively. Continuous long-term use (≥5 years) of low-dose aspirin was associated with a 27% reduction in colorectal cancer risk (OR, 0.73 [CI, 0.54 to 0.99]), whereas the overall OR for cumulative long-term use (continuous or noncontinuous) was close to unity. Nonaspirin NSAID use was associated with a substantial reduction in colorectal cancer risk, particularly for long-term, high-intensity use (average defined daily dose ≥0.3) of agents with high cyclooxygenase-2 selectivity (OR, 0.57 [CI, 0.44 to 0.74]).
Data were unavailable on over-the-counter purchases of high-dose aspirin and low-dose ibuprofen or NSAID dosing schedules, there were several comparisons, and the authors were unable to adjust for confounding by some risk factors.
Long-term, continuous use of low-dose aspirin and long-term use of nonaspirin NSAIDs were associated with reduced colorectal cancer risk. Persons who continuously used low-dose aspirin comprised only a small proportion of the low-dose aspirin users.
Danish Cancer Society, Aarhus University Research Foundation.
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Gastroenterology/Hepatology, Hematology/Oncology, Gastrointestinal Cancer, Colorectal Cancer.
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