Cancer Causes & Control

, Volume 23, Issue 9, pp 1451–1461 | Cite as

Non-steroidal anti-inflammatory drugs, acetaminophen, and risk of skin cancer in the Nurses’ Health Study

  • J. M. Jeter
  • J. Han
  • M. E. Martinez
  • D. S. Alberts
  • A. A. Qureshi
  • D. Feskanich
Original paper



Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with lower risk of certain cancers, but data on the effect on skin cancer risk have been limited and contradictory. We prospectively examined whether use of NSAIDS or acetaminophen was associated with a lower risk of skin cancer in women.


The 92,125 Caucasian women in the Nurses’ Health Study provided information on aspirin use in 1980. Other NSAIDs and acetaminophen were added in 1990. Medication use, frequency, and quantity were reassessed on biennial questionnaires. Through 2008, we confirmed 658 melanoma cases, 1,337 squamous cell carcinoma (SCC) cases, and had 15,079 self-reports of basal cell carcinoma (BCC). We used COX proportional hazards models to compute relative risks (RR) adjusted for known skin cancer risk factors.


Neither aspirin nor non-aspirin NSAID use was associated with a lower risk of melanoma, SCC, or BCC, even for women with high quantity, frequency, or duration of use. Instead, we observed an increased risk of melanoma among current aspirin users (RR = 1.32, 95 % CI 1.03–1.70), though an increase of similar magnitude among past users and lack of a dose–response effect did not support a pharmacologic mechanism. We observed a mild reduction in SCC risk in current acetaminophen users (RR = 0.88, 95 % CI 0.75–1.02), with a linear decrease in risk with greater frequency of use (p = 0.04).


Aspirin and other NSAIDs were not associated with a lower risk of melanoma, SCC, or BCC in women. Our large, prospective study does not support a chemoprotective effect of NSAIDs against skin cancers.


Skin cancer Melanoma Basal cell carcinoma (Cutaneous) Squamous cell carcinoma Aspirin Acetaminophen Non-steroidal anti-inflammatory medications (NSAIDs) 



We are indebted to the participants in the NHS for their dedication to this study. We thank the following state cancer registries for their help: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Virginia, Washington, and Wyoming. This research was supported by R03CA125821, P30CA023074, and P01CA87969 from the National Institutes of Health and a Career Development Award from the American Society for Clinical Oncology.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Lotze MT, Dallal RM, Kirkwood JM, Flickinger JC (2001) Cutaneous melanoma. In: Devita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 6th edn. Lippincott Williams & Wilkins, Philadelphia, PA, pp 2012–2013Google Scholar
  2. 2.
    Demierre M-F, Nathanson L (2003) Chemoprevention of melanoma: an unexplored strategy. J Clin Oncol 21:158–165PubMedCrossRefGoogle Scholar
  3. 3.
    Gruber S, Roush G, Barnhill R (1993) Sensitivity and specificity of self-examination for cutaneous malignant melanoma risk factors. Am J Prevent Med 9:50–53Google Scholar
  4. 4.
    Huang C et al (1997) Inhibition of ultraviolet B-induced activator protein-1 (AP-1) activity by aspirin in AP-1 luciferase transgenic mice. J Biol Chem 272:26325–26331PubMedCrossRefGoogle Scholar
  5. 5.
    Denkert C et al (2001) Expression of cyclooxygenase 2 in human malignant melanoma. Cancer Res 61:303–308PubMedGoogle Scholar
  6. 6.
    Zhang J, Bowden G (2008) UVB irradiation regulates Cox-2 mRNA stability through AMPK and HuR in human keratinocytes. Mol Carcinog 47(12):974–983PubMedCrossRefGoogle Scholar
  7. 7.
    Vogel U et al (2007) Polymorphisms in COX-2, NSAID use and risk of basal cell carcinoma in a prospective study of Danes. Mutat Res 617(1–2):138–146PubMedGoogle Scholar
  8. 8.
    Jeter J, Bonner JD, Johnson TH, Gruber SB (2011) Nonsteroidal anti-inflammatory drugs and risk of melanoma. J Skin Cancer 598571. Epub 2011 May 26Google Scholar
  9. 9.
    Colditz G, Martin P, Stampfer MJ, Willett WC, Sampson L, Rosner B, Hennekens CH, Speizer FE (1986) Validation of questionnaire information on risk factors and disease outcomes in a prospective cohort study of women. Am J Epidemiol 123(5):894–900PubMedGoogle Scholar
  10. 10.
    Hunter D, Colditz GA, Stampfer MJ, Willett WC, Speizer FE (1990) Risk factors for basal cell carcinoma in a prospective cohort of women. Ann Epidemiol 1:13–23PubMedCrossRefGoogle Scholar
  11. 11.
    Holmes M, Chen WY, Li L, Hertzmark E, Spiegelman D, Hankinson SE (2010) Aspirin intake and survival after breast cancer. J Clin Oncol 28(9):1467–1472PubMedCrossRefGoogle Scholar
  12. 12.
    Viswanathan A, Feskanich D, Schernhammer ES, Hankinson SE (2008) Aspirin, NSAID, and acetaminophen use and the risk of endometrial cancer. Cancer Res 68(7):2507–2513PubMedCrossRefGoogle Scholar
  13. 13.
    Fairfield K, Hunter DJ, Fuchs CS, Colditz GA, Hankinson SE (2002) Aspirin, other NSAIDs, and ovarian cancer risk (United States). Cancer Causes Control 13(6):535–542PubMedCrossRefGoogle Scholar
  14. 14.
    Schernhammer E, Kang JH, Chan AT, Michaus DS, Skinner HG, Giovannucci E, Colditz GA, Fuchs CS (2004) A prospective study of aspirin use and the risk of pancreatic cancer in women. J Nat Cancer Inst 96(1):22–28PubMedCrossRefGoogle Scholar
  15. 15.
    Chan A, Manson JE, Feskanich D, Stampfer MJ, Colditz GA, Fuchs CS (2007) Long-term aspirin use and mortality in women. Arch Intern Med 167(6):562–572PubMedCrossRefGoogle Scholar
  16. 16.
    Chan A, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan GC, Fuchs CS (2005) Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colon cancer. JAMA 294(8):914–923PubMedCrossRefGoogle Scholar
  17. 17.
  18. 18.
    Scotto J, Fears TR, Fraumeni JF Jr (1996) In: Schottenfeld D, Fraumeni JF Jr (eds) Cancer epidemiology and prevention, 2nd edn. Oxford University Press, New York, pp 355–372Google Scholar
  19. 19.
    Scotto J, Cotton G, Urbach F, Berger D, Fears T (1988) Biologically effective ultraviolet radiation: surface measurements in the United States, 1974 to 1985. Science 239(4841 pt 1):762–764PubMedCrossRefGoogle Scholar
  20. 20.
    Wolf A, Hunter DJ, Colditz GA, Manson JE, Stampfer MJ, Corsano KA, Rosner B, Kriska A, Willett WC (1994) Reproducibility and validity of a self-administered activity questionnaire. Int J Epidemiol 23:991–999PubMedCrossRefGoogle Scholar
  21. 21.
    Willett W, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J, Hennekens CH, Speizer FE (1985) Reproducibility and validity of a semiquantitative food frequence questionnaire. Am J Epidemiol 122(1):51–65PubMedGoogle Scholar
  22. 22.
    Rimm E, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB, Willett WC (1992) Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am J Epidemiol 135(10):1114–1126PubMedGoogle Scholar
  23. 23.
    Feskanich D, Hunter DJ, Willett WC, Colditz GA (2003) Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women. Br J Cancer 88:1381–1387PubMedCrossRefGoogle Scholar
  24. 24.
    Cho E, Rosner BA, Feskanich D, Colditz GA (2005) Risk factors and individual probabilities of melanoma for whites. J Clin Oncol 23:2669–2675PubMedCrossRefGoogle Scholar
  25. 25.
    Subongkot S et al (2003) Selective cyclooxygenase-2 inhibition: a target in cancer prevention and treatment. Pharmacotherapy 23(1):9–28PubMedCrossRefGoogle Scholar
  26. 26.
    Harris R, Beebe-Zonk J, Namboodiri K (2001) Inverse association of non-steroidal anti-inflammatory drugs and malignant melanoma among women. Oncol Rep 8(3):655–657PubMedGoogle Scholar
  27. 27.
    Joosse A et al (2009) Non-steroidal anti-inflammatory drugs and melanoma risk: large Dutch population-based case–control study. J Invest Dermatol 129(11):2620–2627PubMedCrossRefGoogle Scholar
  28. 28.
    Curiel-Lewandrowski C, Nijsten T, Gomez ML, Hollestein LM, Atkins MB, Stern RS (2011) Long-term use of nonsteroidal anti-inflammatory drugs decreases the risk of cutaneous melanoma: results of a United States case–control study. J Invest Dermatol 131(7):1460–1468. doi: 10.1038/jid.2011.58 PubMedCrossRefGoogle Scholar
  29. 29.
    Asgari M, Maruti S, White E (2008) A large cohort study of nonsteroidal anti-inflammatory drug use and melanoma incidence. J Nat Cancer Inst 100:967–971PubMedCrossRefGoogle Scholar
  30. 30.
    Ramirez C et al (2005) Use of cyclooxygenase inhibitors and risk of melanoma in high-risk patients. Dermatol Surg 31:748–753PubMedCrossRefGoogle Scholar
  31. 31.
    Butler G et al (2005) Nonsteroidal anti-inflammatory drugs and the risk of actinic keratoses and squamous cell cancers of the skin. J Am Acad Dermatol 53(6):966–972PubMedCrossRefGoogle Scholar
  32. 32.
    Asgari M, Chren M–M, Warton EM, Friedman GD, White E (2010) Association between nonsteroidal anti-inflammatory drug use and cutaneous squamous cell carcinoma. Arch Dermatol 146(4):388–395PubMedCrossRefGoogle Scholar
  33. 33.
    Clouser M et al (2009) Effect of non-steroidal anti-inflammatory drugs on non-melanoma skin cancer incidence in the SKICAP-AK trial. Pharmacoepidemiol Drug Saf 18(4):276–283PubMedCrossRefGoogle Scholar
  34. 34.
    Glau M et al (2006) Effect of NSAIDs on the recurrence of nonmelanoma skin cancer. Int J Cancer 119(3):682–686CrossRefGoogle Scholar
  35. 35.
    Tang J et al (2010) Basal cell carcinoma chemoprevention with nonsteroidal anti-inflammatory drugs in genetically predisposed PTCH1 ± humans and mice. Cancer Prev Res 3(1):25–34CrossRefGoogle Scholar
  36. 36.
    Elmets C, Viner JL, Pentland AP, Cantrell W, Lin H-Y, Bailey H, Kang S, Linden KG, Heffernan M, Duvic M, Richmond E, Elewski BE, Umar A, Bell W, Gordon GB (2010) Chemoprevention of nonmelanoma skin cancer with celecoxib: a randomized, double-blind, placebo-controlled trial. J Nat Cancer Inst 102:1–10CrossRefGoogle Scholar
  37. 37.
    Vad N et al (2009) Efficacy of acetaminophen in skin B16–F0 melanoma tumor-bearing C57BL/6 mice. Int J Oncol 35(1):193–204PubMedGoogle Scholar
  38. 38.
    Vad N et al (2009) Biochemical mechanism of acetaminophen (APAP) induced toxicity in melanoma cell lines. J Pharm Sci 98(4):1409–1425PubMedCrossRefGoogle Scholar
  39. 39.
    Scherer D, Kumar R (2010) Genetics of pigmentation in skin cancer—a review. Mutat Res 705(2):141–153PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • J. M. Jeter
    • 1
    • 2
  • J. Han
    • 3
    • 4
    • 5
  • M. E. Martinez
    • 6
  • D. S. Alberts
    • 1
    • 2
  • A. A. Qureshi
    • 3
    • 4
  • D. Feskanich
    • 3
  1. 1.Department of MedicineUniversity of Arizona College of MedicineTucsonUSA
  2. 2.Arizona Cancer CenterTucsonUSA
  3. 3.Channing Laboratory, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  4. 4.Clinical Research Program, Department of Dermatology, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  5. 5.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  6. 6.Moores UCSD Cancer CenterUniversity of CaliforniaSan Diego, La JollaUSA

Personalised recommendations