Cancer Causes & Control

, Volume 23, Issue 3, pp 431–444 | Cite as

Non-steroidal anti-inflammatory drugs and cancer incidence by sex in the VITamins And Lifestyle (VITAL) cohort

  • Theodore M. BraskyEmail author
  • John D. Potter
  • Alan R. Kristal
  • Ruth E. Patterson
  • Ulrike Peters
  • Maryam M. Asgari
  • Mark D. Thornquist
  • Emily White
Original paper



Use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of several cancers. A recent meta-analysis of randomized trials of aspirin reported a reduction in cancer mortality; however, few studies have investigated whether aspirin or other NSAIDs reduce overall cancer risk.


64,847 residents of western Washington State, aged 50–76, completed a baseline questionnaire in 2000–2002 and reported on their use of individual NSAIDs over the past 10 years. Behavior was categorized as non-use, low (<4 days/week or <4 years), and high (≥4 days/week and ≥4 years). Over 7 years of follow-up, 5,946 incident invasive cancer cases were identified. Multivariable proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).


Relative to non-use, high 10-year use of regular-strength NSAIDs was inversely associated with total cancer risk in men (HR 0.88, 95% CI: 0.79–0.97) and not associated with risk in women (HR 1.10, 95% CI: 0.96–1.25; p interaction <0.01). Use of regular-strength NSAIDs was strongly and inversely associated with colorectal cancer risk in men and women, but differentially associated with sex-specific risk of shared cancer sites other than colorectal cancer (men: HR 0.83, 95% CI: 0.71–0.97; women: HR 1.18, 95% CI: 0.97–1.44; p interaction < 0.01).


Long-term use of NSAIDs was associated with a reduced risk of total cancer among men and colorectal cancer among both sexes. Our findings do not support NSAID use for overall cancer prevention among women. Additional high-quality studies with long-term follow-up for cancer among women are needed before a public health recommendation can be made.


Aspirin Ibuprofen Non-steroidal anti-inflammatory drugs Total cancer 



This work is supported by National Institutes of Health and National Cancer Institute grants R25-CA094880 and K05-CA154337.

Supplementary material

10552_2011_9891_MOESM1_ESM.docx (49 kb)
Supplementary material 1 (DOCX 49 kb)


  1. 1.
    Harris RE, Beebe-Donk J, Doss H, Burr Doss D (2005) Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (review). Oncol Rep 13:559–583PubMedGoogle Scholar
  2. 2.
    Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW (2011) Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 377:31–41PubMedCrossRefGoogle Scholar
  3. 3.
    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
  4. 4.
    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 99:608–615PubMedCrossRefGoogle Scholar
  5. 5.
    Bardia A, Ebbert JO, Vierkant RA et al (2007) Association of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs with cancer incidence and mortality. J Natl Cancer Inst 99:881–889PubMedCrossRefGoogle Scholar
  6. 6.
    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 88:1687–1692PubMedCrossRefGoogle Scholar
  7. 7.
    Schreinemachers DM, Everson RB (1994) Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology 5:138–146PubMedCrossRefGoogle Scholar
  8. 8.
    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 88:684–688PubMedCrossRefGoogle Scholar
  9. 9.
    White E, Patterson RE, Kristal AR et al (2004) VITamins And Lifestyle cohort study: study design and characteristics of supplement users. Am J Epidemiol 159:83–93PubMedCrossRefGoogle Scholar
  10. 10.
    Kim MA, Kim CJ, Seo JB et al (2011) The effect of aspirin on C-reactive protein in hypertensive patients. Clin Exp Hypertens 33:47–52PubMedCrossRefGoogle Scholar
  11. 11.
    Menzies D, Nair A, Meldrum KT, Hopkinson P, Lipworth BJ (2008) Effect of aspirin on airway inflammation and pulmonary function in patients with persistent asthma. J Allergy Clin Immunol 121:1184–1189Google Scholar
  12. 12.
    Littman AJ, Kristal AR, White E (2006) Recreational physical activity and prostate cancer risk (United States). Cancer Causes Control 17:831–841PubMedCrossRefGoogle Scholar
  13. 13.
    WCRF/AICR (2007) Food, nutrition and the prevention of cancer: a global perspective. AICR, WashingtonGoogle Scholar
  14. 14.
    Danesh J, Wheeler JG, Hirschfield GM et al (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. New Engl J Med 350:1387–1397PubMedCrossRefGoogle Scholar
  15. 15.
    Pierce BL, Neuhouser ML, Wener MH et al (2009) Correlates of circulating C-reactive protein and serum amyloid A concentrations in breast cancer survivors. Breast Cancer Res Treat 114:155–167PubMedCrossRefGoogle Scholar
  16. 16.
    Koenig W, Sund M, Frohlich M, Lowel H, Hutchinson WL, Pepys MB (2003) Refinement of the association of serum C-reactive protein concentration and coronary heart disease risk by correction for within-subject variation over time: the MONICA Augsburg studies, 1984 and 1987. Am J Epidemiol 158:357–364PubMedCrossRefGoogle Scholar
  17. 17.
    Bielecka-Dabrowa A, Goch JH, Mikhailidis DP, Rysz J, Maciejewski M, Banach M (2009) The influence of atorvastatin on parameters of inflammation and function of the left ventricle in patients with dilated cardiomyopathy. Med Sci Monit 15:MS12–MS23Google Scholar
  18. 18.
    Harris NL, Jaffe ES, Diebold J et al (1999) The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. Ann Oncol 10:1419–1432Google Scholar
  19. 19.
    Harris NL, Jaffe ES, Diebold J et al (1999) World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 17:3835–3849PubMedGoogle Scholar
  20. 20.
    Rothwell PM, Wilson M, Elwin CE et al (2010) Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 376:1741–1750PubMedCrossRefGoogle Scholar
  21. 21.
    Cole BF, Logan RF, Halabi S et al (2009) Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst 101:256–266PubMedCrossRefGoogle Scholar
  22. 22.
    Ready A, Velicer CM, McTiernan A, White E (2008) NSAID use and breast cancer risk in the VITAL cohort. Breast Cancer Res Treat 109:533–543PubMedCrossRefGoogle Scholar
  23. 23.
    Brasky TM, Velicer CM, Kristal AR, Peters U, Potter JD, White E (2010) Nonsteroidal anti-inflammatory drugs and prostate cancer risk in the VITamins And Lifestyle (VITAL) cohort. Cancer Epidemiol Biomarkers Prev 19:3185–3188PubMedCrossRefGoogle Scholar
  24. 24.
    Slatore CG, Au DH, Littman AJ, Satia JA, White E (2009) Association of nonsteroidal anti-inflammatory drugs with lung cancer: results from a large cohort study. Cancer Epidemiol Biomarkers Prev 18:1203–1207PubMedCrossRefGoogle Scholar
  25. 25.
    Asgari MM, Maruti SS, White E (2008) A large cohort study of nonsteroidal anti-inflammatory drug use and melanoma incidence. J Natl Cancer Inst 100:967–971PubMedCrossRefGoogle Scholar
  26. 26.
    Walter RB, Milano F, Brasky TM, White E (2011, in press) Long-term use of acetaminophen, aspirin, and other non-steroidal anti-inflammatory drugs and risk of hematologic malignancies: results from the prospective VITamins And Lifestyle (VITAL) study. J Clin Oncol 29(17):2424–2431Google Scholar
  27. 27.
    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 294:914–923PubMedCrossRefGoogle Scholar
  28. 28.
    Takkouche B, Regueira-Mendez C, Etminan M (2008) Breast cancer and use of nonsteroidal anti-inflammatory drugs: a meta-analysis. J Natl Cancer Inst 100:1420–1423Google Scholar
  29. 29.
    Bonovas S, Filioussi K, Sitaras NM (2005) Do nonsteroidal anti-inflammatory drugs affect the risk of developing ovarian cancer? A meta-analysis. Br J Clin Pharmacol 60:194–203PubMedCrossRefGoogle Scholar
  30. 30.
    Khuder SA, Herial NA, Mutgi AB, Federman DJ (2005) Nonsteroidal antiinflammatory drug use and lung cancer: a metaanalysis. Chest 127:748–754PubMedCrossRefGoogle Scholar
  31. 31.
    Gonzalez-Perez A, Garcia Rodriguez LA, Lopez-Ridaura R (2003) Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis. BMC Cancer 3:28Google Scholar
  32. 32.
    Cerhan JR, Anderson KE, Janney CA, Vachon CM, Witzig TE, Habermann TM (2003) Association of aspirin and other non-steroidal anti-inflammatory drug use with incidence of non-Hodgkin lymphoma. Int J Cancer 106:784–788PubMedCrossRefGoogle Scholar
  33. 33.
    Baker JA, Weiss JR, Czuczman MS, Menezes RJ, Ambrosone CB, Moysich KB (2005) Regular use of aspirin or acetaminophen and risk of non-Hodgkin lymphoma. Cancer Causes Control 16:301–308PubMedCrossRefGoogle Scholar
  34. 34.
    Baigent C, Blackwell L, Collins R et al (2009) Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 373:1849–1860PubMedCrossRefGoogle Scholar
  35. 35.
    Adelman EE, Lisabeth L, Brown DL (2011) Gender differences in the primary prevention of stroke with aspirin. Women’s Health (London, England) 7:341–352; quiz 52–3Google Scholar
  36. 36.
    Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL (2006) Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 295:306–313PubMedCrossRefGoogle Scholar
  37. 37.
    Navarro SL, Saracino MR, Makar KW et al (2011) Determinants of aspirin metabolism in healthy men and women: effects of dietary inducers of UDP-glucuronosyltransferases. J Nutrigenet Nutrigenomics 4:110–118PubMedCrossRefGoogle Scholar
  38. 38.
    Waxman DJ, Holloway MG (2009) Sex differences in the expression of hepatic drug metabolizing enzymes. Mol Pharmacol 76:215–228PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Theodore M. Brasky
    • 1
    • 2
    Email author
  • John D. Potter
    • 1
    • 2
  • Alan R. Kristal
    • 1
    • 2
  • Ruth E. Patterson
    • 3
  • Ulrike Peters
    • 1
    • 2
  • Maryam M. Asgari
    • 4
  • Mark D. Thornquist
    • 1
    • 2
  • Emily White
    • 1
    • 2
  1. 1.The Fred Hutchinson Cancer Research Center, Cancer Prevention UnitSeattleUSA
  2. 2.Department of EpidemiologyUniversity of WashingtonSeattleUSA
  3. 3.Department of Family and Preventive MedicineUniversity of California—San DiegoSan DiegoUSA
  4. 4.Kaiser Permanente Division of ResearchOaklandUSA

Personalised recommendations