Cancer Causes & Control

, Volume 20, Issue 5, pp 731–740 | Cite as

Aspirin and other non-steroidal anti-inflammatory drugs and risk of colorectal cancer: A Danish cohort study

  • Søren Friis
  • Aslak H. Poulsen
  • Henrik Toft Sørensen
  • Anne Tjønneland
  • Kim Overvad
  • Ulla Vogel
  • Joseph K. McLaughlin
  • William J. Blot
  • Jørgen H. Olsen
Original Paper



The optimal duration and dose of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) in the potential prevention of colorectal cancer (CRC) have not been established. We examined this issue in the Danish Diet, Cancer, and Health Study.


Self-reported NSAID use at entry (January 1995–May 1997) was updated through June 2006, using a nationwide prescription database. CRC incidence was ascertained from nationwide registers. Cox proportional hazards regression was used to compute confounder-adjusted incidence rate ratios (RRs) and 95% confidence intervals (CIs).


From 51,053 cohort subjects, we identified 615 CRC cases during 1995–2006. Daily aspirin use at entry was associated with a decreased risk of CRC (RR, 0.73; 95% CI, 0.49–1.10). A similar risk reduction was seen among subjects with 10 or more prescriptions for aspirin or non-aspirin NSAIDs and five or more years of follow-up. Most aspirin prescriptions were for 75–150 mg aspirin tablets. Among non-aspirin NSAID users, only those with body mass index (BMI) above 25 showed risk reductions [RR, 0.69 (0.47–1.03) for 10 or more prescriptions].


Long-term consistent use of aspirin or non-aspirin NSAIDs appears necessary to achieve a protective effect against CRC. Further studies of the effective dose of aspirin and the potential interaction between NSAID use and BMI are warranted.


Non-steroidal anti-inflammatory agents Colorectal neoplasms Risk Epidemiology Cohort study 



We thank Mathias Budinger, MSc, Institute of Medical Biometry, Epidemiology, and Informatics, Johannes Gutenberg University, Mainz, Germany, for help with the data management.


  1. 1.
    Ulrich CM, Bigler J, Potter JD (2006) Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer 6:130–140. doi: 10.1038/nrc1801 PubMedCrossRefGoogle Scholar
  2. 2.
    Dube C, Rostom A, Lewin G et al (2007) The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 146:365–375PubMedGoogle Scholar
  3. 3.
    Rostom A, Dube C, Lewin G et al (2007) Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 146:376–389PubMedGoogle Scholar
  4. 4.
    U.S. Preventive Services Task Force (2007) Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 146:361–364Google Scholar
  5. 5.
    Baron JA, Cole BF, Sandler RS et al (2003) A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 348:891–899. doi: 10.1056/NEJMoa021735 PubMedCrossRefGoogle Scholar
  6. 6.
    Sandler RS, Halabi S, Baron JA et al (2003) A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 348:883–890. doi: 10.1056/NEJMoa021633 PubMedCrossRefGoogle Scholar
  7. 7.
    Benamouzig R, Deyra J, Martin A et al (2003) Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology 125:328–336. doi: 10.1016/S0016-5085(03)00887-4 PubMedCrossRefGoogle Scholar
  8. 8.
    Logan RF, Grainge MJ, Shepherd VC, Armitage NC, Muir KR (2008) Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 134:29–38. doi: 10.1053/j.gastro.2007.10.014 PubMedCrossRefGoogle Scholar
  9. 9.
    Giardiello FM, Hamilton SR, Krush AJ et al (1993) Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 328:1313–1316. doi: 10.1056/NEJM199305063281805 PubMedCrossRefGoogle Scholar
  10. 10.
    Arber N, Eagle CJ, Spicak J et al (2006) Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 355:885–895. doi: 10.1056/NEJMoa061652 PubMedCrossRefGoogle Scholar
  11. 11.
    Bertagnolli MM, Eagle CJ, Zauber AG et al (2006) Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 355:873–884. doi: 10.1056/NEJMoa061355 PubMedCrossRefGoogle Scholar
  12. 12.
    Baron JA, Sandler RS, Bresalier RS et al (2006) A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology 131:1674–1682. doi: 10.1053/j.gastro.2006.08.079 PubMedCrossRefGoogle Scholar
  13. 13.
    Gann PH, Manson JE, Glynn RJ, Buring JE, Hennekens CH (1993) Low-dose aspirin and incidence of colorectal tumors in a randomized trial. J Natl Cancer Inst 85:1220–1224. doi: 10.1093/jnci/85.15.1220 PubMedCrossRefGoogle Scholar
  14. 14.
    Cook NR, Lee IM, Gaziano JM et al (2005) Low-dose aspirin in the primary prevention of cancer: the Women’s Health Study: a randomized controlled trial. JAMA 294:47–55. doi: 10.1001/jama.294.1.47 PubMedCrossRefGoogle Scholar
  15. 15.
    Flossmann E, Rothwell PM (2007) Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet 369:1603–1613. doi: 10.1016/S0140-6736(07)60747-8 PubMedCrossRefGoogle Scholar
  16. 16.
    Thun MJ, Namboodiri MM, Calle EE, Flanders WD, Heath CW Jr (1993) Aspirin use and risk of fatal cancer. Cancer Res 53:1322–1327PubMedGoogle Scholar
  17. 17.
    Collet JP, Sharpe C, Belzile E, Boivin JF, Hanley J, Abenhaim L (1999) Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing. Br J Cancer 81:62–68. doi: 10.1038/sj.bjc.6690651 PubMedCrossRefGoogle Scholar
  18. 18.
    Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan GC, Fuchs CS (2005) Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA 294:914–923. doi: 10.1001/jama.294.8.914 PubMedCrossRefGoogle Scholar
  19. 19.
    Allison M, Garland C, Chlebowski R et al (2006) The association between aspirin use and the incidence of colorectal cancer in women. Am J Epidemiol 164:567–575. doi: 10.1093/aje/kwj250 PubMedCrossRefGoogle Scholar
  20. 20.
    Larsson SC, Giovannucci E, Wolk A (2006) Long-term aspirin use and colorectal cancer risk: a cohort study in Sweden. Br J Cancer 95:1277–1279. doi: 10.1038/sj.bjc.6603442 PubMedCrossRefGoogle Scholar
  21. 21.
    Jacobs EJ, Thun MJ, Bain EB, Rodriguez C, Henley SJ, Calle EE (2007) A large cohort study of long-term daily use of adult-strength aspirin and cancer incidence. J Natl Cancer Inst 99:608–615. doi: 10.1093/jnci/djk132 PubMedCrossRefGoogle Scholar
  22. 22.
    Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Wu K, Fuchs CS (2008) Aspirin dose and duration of use and risk of colorectal cancer in men. Gastroenterology 134:21–28. doi: 10.1053/j.gastro.2007.09.035 PubMedCrossRefGoogle Scholar
  23. 23.
    Rosenberg L, Palmer JR, Zauber AG, Warshauer ME, Stolley PD, Shapiro S (1991) A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. J Natl Cancer Inst 83:355–358. doi: 10.1093/jnci/83.5.355 PubMedCrossRefGoogle Scholar
  24. 24.
    Smalley W, Ray WA, Daugherty J, Griffin MR (1999) Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study. Arch Intern Med 159:161–166. doi: 10.1001/archinte.159.2.161 PubMedCrossRefGoogle Scholar
  25. 25.
    Garcia-Rodriguez LA, Huerta-Alvarez C (2001) Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Epidemiology 12:88–93. doi: 10.1097/00001648-200101000-00015 PubMedCrossRefGoogle Scholar
  26. 26.
    Sansbury LB, Millikan RC, Schroeder JC, Moorman PG, North KE, Sandler RS (2005) Use of nonsteroidal antiinflammatory drugs and risk of colon cancer in a population-based, case-control study of African Americans and Whites. Am J Epidemiol 162:548–558. doi: 10.1093/aje/kwi248 PubMedCrossRefGoogle Scholar
  27. 27.
    Kim S, Baron JA, Mott LA et al (2006) Aspirin may be more effective in preventing colorectal adenomas in patients with higher BMI (United States). Cancer Causes Control 17:1299–1304. doi: 10.1007/s10552-006-0075-x PubMedCrossRefGoogle Scholar
  28. 28.
    Agarwal B, Rao CV, Bhendwal S et al (1999) Lovastatin augments sulindac-induced apoptosis in colon cancer cells and potentiates chemopreventive effects of sulindac. Gastroenterology 117:838–847. doi: 10.1016/S0016-5085(99)70342-2 PubMedCrossRefGoogle Scholar
  29. 29.
    Reddy BS, Wang CX, Kong AN et al (2006) Prevention of azoxymethane-induced colon cancer by combination of low doses of atorvastatin, aspirin, and celecoxib in F 344 rats. Cancer Res 66:4542–4546. doi: 10.1158/0008-5472.CAN-05-4428 PubMedCrossRefGoogle Scholar
  30. 30.
    Hoffmeister M, Chang-Claude J, Brenner H (2007) Individual and joint use of statins and low-dose aspirin and risk of colorectal cancer: a population-based case-control study. Int J Cancer 121:1325–1330. doi: 10.1002/ijc.22796 PubMedCrossRefGoogle Scholar
  31. 31.
    Xiao H, Yang CS (2008) Combination regimen with statins and NSAIDs: a promising strategy for cancer chemoprevention. Int J Cancer 123:983–990. doi: 10.1002/ijc.23718 PubMedCrossRefGoogle Scholar
  32. 32.
    Bonovas S, Filioussi K, Flordellis CS, Sitaras NM (2007) Statins and the risk of colorectal cancer: a meta-analysis of 18 studies involving more than 1.5 million patients. J Clin Oncol 25:3462–3468. doi: 10.1200/JCO.2007.10.8936 PubMedCrossRefGoogle Scholar
  33. 33.
    Hawk ET, Levin B (2005) Colorectal cancer prevention. J Clin Oncol 23:378–391. doi: 10.1200/JCO.2005.08.097 PubMedCrossRefGoogle Scholar
  34. 34.
    DuPont AW, Arguedas MR, Wilcox CM (2007) Aspirin chemoprevention in patients with increased risk for colorectal cancer: a cost-effectiveness analysis. Aliment Pharmacol Ther 26:431–441PubMedCrossRefGoogle Scholar
  35. 35.
    Tjønneland A, Olsen A, Boll K et al (2007) Study design, exposure variables, and socioeconomic determinants of participation in Diet, Cancer and Health: a population-based prospective cohort study of 57,053 men and women in Denmark. Scand J Public Health 35:432–441. doi: 10.1080/14034940601047986 PubMedCrossRefGoogle Scholar
  36. 36.
    Andersen TF, Madsen M, Jørgensen J, Mellemkjær L, Olsen JH (1999) The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull 46:263–268PubMedGoogle Scholar
  37. 37.
    Gaist D, Sørensen HT, Hallas J (1997) The Danish prescription registries. Dan Med Bull 44:445–448PubMedGoogle Scholar
  38. 38.
    Frank L (2000) Epidemiology. When an entire country is a cohort. Science 287:2398–2399. doi: 10.1126/science.287.5462.2398 PubMedCrossRefGoogle Scholar
  39. 39.
    World Health Organization Collaborating Centre for Drug Statistics Methodology (2001) Guidelines for ATC classification and DDD assignments. World Health Organization Collaborating Centre for Drug Statistics Methodology, OsloGoogle Scholar
  40. 40.
    Sørensen HT, Friis S, Nørgård B et al (2003) Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study. Br J Cancer 88:1687–1692. doi: 10.1038/sj.bjc.6600945 PubMedCrossRefGoogle Scholar
  41. 41.
    Danish Board of Health (1995) Danish Classification of Surgical Procedures and Therapies. Danish Board of Health, CopenhagenGoogle Scholar
  42. 42.
    Storm HH, Michelsen EV, Clemmensen IH, Pihl J (1997) The Danish Cancer Registry—history, content, quality and use. Dan Med Bull 44:535–539PubMedGoogle Scholar
  43. 43.
    Vyberg M, Bjerregaard B, Bak M, Gram I, Hvolris H (2005) Pathology database. Danish Society of Pathologic Anatomy and Cytology. Ugeskr Laeger 167:1401PubMedGoogle Scholar
  44. 44.
    National Board of Health (2006) Cancer incidence in Denmark, 2001. National Board of Health, Copenhagen, DenmarkGoogle Scholar
  45. 45.
    Engholm G, Storm HH, Ferlay J et al. (2008) NORDCAN: cancer incidence, mortality and prevalence in the Nordic Countries. Association of Nordic Cancer Registries. Danish Cancer Society, Copenhagen Google Scholar
  46. 46.
    World Health Organization (2000) Obesity: preventing and managing the global epidemic. WHO Technical Report Series No 894. World Health Organization, GenevaGoogle Scholar
  47. 47.
    Danish Medicines Agency (2008) Medicinal Product Statistics in Denmark 2003–2007. Danish Medicines Agency, CopenhagenGoogle Scholar
  48. 48.
    Vinogradova Y, Hippisley-Cox J, Coupland C, Logan RF (2007) Risk of colorectal cancer in patients prescribed statins, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 inhibitors: nested case-control study. Gastroenterology 133:393–402. doi: 10.1053/j.gastro.2007.05.023 PubMedCrossRefGoogle Scholar
  49. 49.
    Friis S, Sørensen HT, McLaughlin JK, Johnsen SP, Blot WJ, Olsen JH (2003) A population-based cohort study of the risk of colorectal and other cancers among users of low-dose aspirin. Br J Cancer 88:684–688. doi: 10.1038/sj.bjc.6600760 PubMedCrossRefGoogle Scholar
  50. 50.
    World Cancer Research Fund/American Institute for Cancer Research (2007) Food, nutrition, physical activity, and the prevention of cancer: a global perspective. AICR, Washington DCGoogle Scholar
  51. 51.
    Pischon T, Nothlings U, Boeing H (2008) Obesity and cancer. Proc Nutr Soc 67:128–145. doi: 10.1017/S0029665108006976 PubMedCrossRefGoogle Scholar
  52. 52.
    Gunter MJ, Leitzmann MF (2006) Obesity and colorectal cancer: epidemiology, mechanisms and candidate genes. J Nutr Biochem 17:145–156. doi: 10.1016/j.jnutbio.2005.06.011 PubMedCrossRefGoogle Scholar
  53. 53.
    Gupta RA, DuBois RN (2001) Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 1:11–21PubMedCrossRefGoogle Scholar
  54. 54.
    Subbaramaiah K, Dannenberg AJ (2003) Cyclooxygenase 2: a molecular target for cancer prevention and treatment. Trends Pharmacol Sci 24:96–102. doi: 10.1016/S0165-6147(02)00043-3 PubMedCrossRefGoogle Scholar
  55. 55.
    Slattery ML, Samowitz W, Hoffman M, Ma KN, Levin TR, Neuhausen S (2004) Aspirin, NSAIDs, and colorectal cancer: possible involvement in an insulin-related pathway. Cancer Epidemiol Biomarkers Prev 13:538–545PubMedGoogle Scholar
  56. 56.
    Olsen JH, Friis S, Poulsen AH et al (2008) Use of NSAIDs, smoking and lung cancer risk. Br J Cancer 98:232–237. doi: 10.1038/sj.bjc.6604151 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Søren Friis
    • 1
  • Aslak H. Poulsen
    • 1
  • Henrik Toft Sørensen
    • 2
  • Anne Tjønneland
    • 1
  • Kim Overvad
    • 3
  • Ulla Vogel
    • 4
    • 5
  • Joseph K. McLaughlin
    • 6
    • 7
  • William J. Blot
    • 6
    • 7
  • Jørgen H. Olsen
    • 1
  1. 1.Institute of Cancer EpidemiologyDanish Cancer SocietyCopenhagenDenmark
  2. 2.Department of Clinical EpidemiologyAarhus University HospitalAarhusDenmark
  3. 3.Department of Cardiology and Department of Clinical EpidemiologyAarhus University HospitalAalborgDenmark
  4. 4.National Food InstituteTechnical University of Denmark SøborgDenmark
  5. 5.Institute for Science, Systems and ModelsUniversity of RoskildeRoskildeDenmark
  6. 6.International Epidemiology InstituteRockvilleUSA
  7. 7.Department of MedicineVanderbilt University Medical Center, Vanderbilt-Ingram Cancer CenterNashvilleUSA

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