Cancer Causes & Control

, Volume 26, Issue 7, pp 973–981 | Cite as

Use of nonsteroidal anti-inflammatory drugs and risk of endometrial cancer: a nationwide case–control study

  • Nanna Brøns
  • Louise Baandrup
  • Christian Dehlendorff
  • Susanne K. Kjaer
Original paper



We examined the association between use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and endometrial cancer risk in a nationwide case–control study.


Cases were all women in Denmark diagnosed with endometrial cancer during 2000–2009. Age-matched female controls were randomly selected by risk-set sampling. Information on NSAID use was collected from the Prescription Registry and classified according to duration and intensity. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs), adjusting for potential confounders. Analyses were stratified by endometrial cancer type, and potential effect modification by parity, obesity, and hormone replacement therapy (HRT) use was investigated.


We identified 5,382 endometrial cancer cases and 72,127 controls. Endometrial cancer was not associated with use of low-dose aspirin (OR 0.97, 95 % CI 0.89–1.05) or non-aspirin NSAIDs (OR 0.96, 95 % CI 0.91–1.02) compared with nonuse. The ORs did not vary with increasing duration or intensity of NSAID use or with type of endometrial cancer. Interaction analyses showed reduced endometrial cancer risk associated with low-dose aspirin use among nulliparous women (OR 0.82, 95 % CI 0.70–0.95) and with non-aspirin NSAID use among women having used HRT (OR 0.90, 95 % CI 0.82–0.99).


We found no association between use of NSAIDs and endometrial cancer risk overall, although there were some indications of risk reductions associated with low-dose aspirin use among nulliparous women and with non-aspirin NSAID use among women having used HRT.


Endometrial cancer Nonsteroidal anti-inflammatory drugs Aspirin Chemoprevention Case–control study 



NB was funded by a scholarship from the Lundbeck Foundation. The funding source had no role in the design, analysis, and interpretation of the results.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10552_2015_578_MOESM1_ESM.doc (32 kb)
Supplementary material 1 (doc 32 kb)


  1. 1.
    Sorosky JI (2012) Endometrial cancer. Obstet Gynecol 120:383–397PubMedCrossRefGoogle Scholar
  2. 2.
    Akhmedkhanov A, Zeleniuch-Jacquotte A, Toniolo P (2001) Role of exogenous and endogenous hormones in endometrial cancer: review of the evidence and research perspectives. Ann N Y Acad Sci 943:296–315PubMedCrossRefGoogle Scholar
  3. 3.
    Siiteri PK (1978) Steroid hormones and endometrial cancer. Cancer Res 38:4360–4366PubMedGoogle Scholar
  4. 4.
    Modugno F, Ness RB, Chen C, Weiss NS (2005) Inflammation and endometrial cancer: a hypothesis. Cancer Epidemiol Biomarkers Prev 14:2840–2847PubMedCrossRefGoogle Scholar
  5. 5.
    Wallace AE, Gibson DA, Saunders PT, Jabbour HN (2010) Inflammatory events in endometrial adenocarcinoma. J Endocrinol 206:141–157PubMedCrossRefGoogle Scholar
  6. 6.
    Neill AS, Nagle CM, Protani MM, Obermair A, Spurdle AB, Webb PM (2013) Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: a case-control study, systematic review and meta-analysis. Int J Cancer 132:1146–1155PubMedCrossRefGoogle Scholar
  7. 7.
    Ulrich CM, Bigler J, Potter JD (2006) Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer 6:130–140PubMedCrossRefGoogle Scholar
  8. 8.
    Thun MJ, Jacobs EJ, Patrono C (2012) The role of aspirin in cancer prevention. Nat Rev Clin Oncol 9:259–267PubMedCrossRefGoogle Scholar
  9. 9.
    Ohno S, Ohno Y, Suzuki N et al (2005) Multiple roles of cyclooxygenase-2 in endometrial cancer. Anticancer Res 25:3679–3687PubMedGoogle Scholar
  10. 10.
    Kilic G, Gurates B, Garon J et al (2005) Expression of cyclooxygenase-2 in endometrial adenocarcinoma. Eur J Gynaecol Oncol 26:271–274PubMedGoogle Scholar
  11. 11.
    Gao J, Niwa K, Sun W et al (2004) Non-steroidal anti-inflammatory drugs inhibit cellular proliferation and upregulate cyclooxygenase-2 protein expression in endometrial cancer cells. Cancer Sci 95:901–907PubMedCrossRefGoogle Scholar
  12. 12.
    Ozalp SS, Eren CY, Bostancioglu RB, Koparal AT (2012) Induction of apoptosis and inhibition of cell proliferation by the cyclooxgenase enzyme blocker nimesulide in the Ishikawa endometrial cancer cell line. Eur J Obstet Gynecol Reprod Biol 164:79–84PubMedCrossRefGoogle Scholar
  13. 13.
    Friis S, Sorensen 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 88:684–688PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Sorensen HT, Friis S, Norgard B et al (2003) Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study. Br J Cancer 88:1687–1692PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Danforth KN, Gierach GL, Brinton LA et al (2009) Nonsteroidal anti-inflammatory drug use and endometrial cancer risk in the NIH-AARP Diet and Health Study. Cancer Prev Res 2:466–472CrossRefGoogle Scholar
  16. 16.
    Prizment AE, Folsom AR, Anderson KE (2010) Nonsteroidal anti-inflammatory drugs and risk for ovarian and endometrial cancers in the Iowa Women’s Health Study. Cancer Epidemiol Biomarkers Prev 19:435–442PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Schreinemachers DM, Everson RB (1994) Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology 5:138–146PubMedCrossRefGoogle Scholar
  18. 18.
    Brasky TM, Moysich KB, Cohn DE, White E (2013) Non-steroidal anti-inflammatory drugs and endometrial cancer risk in the VITamins And Lifestyle (VITAL) cohort. Gynecol Oncol 128:113–119PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Phipps AI, Anderson GL, Cochrane BB et al (2012) Migraine history, nonsteroidal anti-inflammatory drug use, and risk of postmenopausal endometrial cancer. Horm Cancer 3:240–248PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Setiawan VW, Matsuno RK, Lurie G et al (2012) Use of nonsteroidal anti-inflammatory drugs and risk of ovarian and endometrial cancer: the Multiethnic Cohort. Cancer Epidemiol Biomarkers Prev 21:1441–1449PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Blenstrup LT, Knudsen LB (2011) Danish registers on aspects of reproduction. Scand J Public Health 39:79–82PubMedCrossRefGoogle Scholar
  22. 22.
    Gjerstorff ML (2011) The Danish Cancer Registry. Scand J Public Health 39:42–45PubMedCrossRefGoogle Scholar
  23. 23.
    Jensen VM, Rasmussen AW (2011) Danish education registers. Scand J Public Health 39:91–94PubMedCrossRefGoogle Scholar
  24. 24.
    Kildemoes HW, Sorensen HT, Hallas J (2011) The Danish National Prescription Registry. Scand J Public Health 39:38–41PubMedCrossRefGoogle Scholar
  25. 25.
    Lynge E, Sandegaard JL, Rebolj M (2011) The Danish National Patient Register. Scand J Public Health 39:30–33PubMedCrossRefGoogle Scholar
  26. 26.
    Pedersen CB (2011) The Danish Civil Registration System. Scand J Public Health 39:22–25PubMedCrossRefGoogle Scholar
  27. 27.
    Rothman K, Greenland S, Lash TL, Rothman K, Greenland S, Lash TL (2008) Case-control studies. Modern epidemiology, 3rd edn. Lippincott Williams & Wilkins, Philadelphia, pp 111–127Google Scholar
  28. 28.
    Schmidt M, Hallas J, Friis S (2014) Potential of prescription registries to capture individual-level use of aspirin and other nonsteroidal anti-inflammatory drugs in Denmark: trends in utilization 1999–2012. Clin Epidemiol 6:155–168PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    ATC Classification Index with DDDs. World Health Organization Collaborating Centre for Drug Statistics Methodology. Accessed 16 Oct 2014
  30. 30.
    Ray WA (2003) Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 158:915–920PubMedCrossRefGoogle Scholar
  31. 31.
    R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. Accessed 2 Nov 2014
  32. 32.
    Brasky TM, Liu J, White E et al (2014) Non-steroidal anti-inflammatory drugs and cancer risk in women: results from the Women’s Health Initiative. Int J Cancer 135:1869–1883PubMedCrossRefGoogle Scholar
  33. 33.
    Fortuny J, Sima C, Bayuga S et al (2009) Risk of endometrial cancer in relation to medical conditions and medication use. Cancer Epidemiol Biomarkers Prev 18:1448–1456PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Bodelon C, Doherty JA, Chen C, Rossing MA, Weiss NS (2009) Use of nonsteroidal antiinflammatory drugs and risk of endometrial cancer. Am J Epidemiol 170:1512–1517PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Viswanathan AN, Feskanich D, Schernhammer ES, Hankinson SE (2008) Aspirin, NSAID, and acetaminophen use and the risk of endometrial cancer. Cancer Res 68:2507–2513PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Moysich KB, Baker JA, Rodabaugh KJ, Villella JA (2005) Regular analgesic use and risk of endometrial cancer. Cancer Epidemiol Biomarkers Prev 14:2923–2928PubMedCrossRefGoogle Scholar
  37. 37.
    Bosetti C, Bravi F, Talamini R, Montella M, Negri E, La VC (2010) Aspirin and risk of endometrial cancer: a case-control study from Italy. Eur J Cancer Prev 19:401–403PubMedCrossRefGoogle Scholar
  38. 38.
    Cook NR, Lee IM, Zhang SM (2013) Alternate-day, low-dose aspirin and cancer risk: long-term observational follow-up of a randomized trial. Ann Intern Med 159:77–85PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    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 294:47–55PubMedCrossRefGoogle Scholar
  40. 40.
    Cuzick J, Thorat MA, Bosetti C et al (2014) Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol. doi: 10.1093/annonc/mdu225 PubMedCentralGoogle Scholar
  41. 41.
    Rothwell PM, Price JF, Fowkes FG (2012) Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet 379:1602–1612PubMedCrossRefGoogle Scholar
  42. 42.
    Purdie DM, Green AC (2001) Epidemiology of endometrial cancer. Best Pract Res Clin Obstet Gynaecol 15:341–354PubMedCrossRefGoogle Scholar
  43. 43.
    Harvey AE, Lashinger LM, Hursting SD (2011) The growing challenge of obesity and cancer: an inflammatory issue. Ann N Y Acad Sci 1229:45–52PubMedCrossRefGoogle Scholar
  44. 44.
    Yood MU, Campbell UB, Rothman KJ et al (2007) Using prescription claims data for drugs available over-the-counter (OTC). Pharmacoepidemiol Drug Saf 16:961–968PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Nanna Brøns
    • 1
  • Louise Baandrup
    • 1
  • Christian Dehlendorff
    • 2
  • Susanne K. Kjaer
    • 1
    • 3
  1. 1.Unit of Virus, Lifestyle and GenesDanish Cancer Society Research CenterCopenhagenDenmark
  2. 2.Unit of Statistics, Bioinformatics and RegistryDanish Cancer Society Research CenterCopenhagenDenmark
  3. 3.The Gynecologic Clinic, Juliane Marie Center, RigshospitaletUniversity of CopenhagenCopenhagenDenmark

Personalised recommendations