NSAIDs Protect Against Skin Cancer

Compared with never-users, ever-users had reduced risk for SCCs, malignant melanomas, and certain BCCs.

Experimental models have shown procarcinogenic effects of cyclooxygenase (COX) enzymes, which promote inflammation, facilitate invasion through the basement membrane zone, suppress host antitumor defense mechanisms, inhibit tumor cell apoptosis, and stimulate angiogenesis. Nonsteroidal anti-inflammatory drugs (NSAIDs) block COX activity. These authors examined the association between NSAID use and risk for squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM) in patients with histologically verified cases recorded in the Danish cancer registry between 1991 and 2008. Patients with human immunodeficiency virus infection, organ transplants, or previous cancer diagnoses were excluded.

Overall, NSAID users had a reduction in SCC and MM, but not BCC, compared with those who had never taken NSAIDs. Reduction in risk was associated with duration of NSAID use and dose size. Among long-term, high-dose NSAID users, the risk reduction was 46% for MM, 35% for SCC, and 17% for BCC. The reduced risk for SCC and melanoma was irrespective of anatomic site, but only BCCs sited elsewhere than the head and neck were influenced by NSAID use. Both aspirin and nonselective NSAIDs effectively protected against SCC and MM; newer COX-2 inhibitors were associated with reductions in SCC but not MM. High-dose, long-term use of acetaminophen was associated with a reduced risk for MM and for BCCs other than on the head and neck.

Comment

This evidence confirms the findings of epidemiologic studies showing that nonsteroidal anti-inflammatory drugs protect against skin cancer and two interventional studies showing such an effect with COX-2 inhibitors. The costs and morbidity associated with surgical treatment of nonmelanoma skin cancer (NMSC) and melanoma pose a serious problem. These cancers are among the few with a rising incidence. The use of NSAIDs, many of which are inexpensive and available over-the-counter, for prevention of NMSC and melanoma is attractive, and could have major public health implications, but it is best to wait for more studies before we recommend them. Which NSAIDs are most effective and free of adverse effects and at what dosages is unknown.

Reviewing Author

Craig A. Elmets, MD

Disclosures

Consultant / Advisory board Astellas Pharmaceuticals

EquityVaxin

Grant / Research support NIH; NIH/NCI; Veteran’s Administration; Ferndale Laboratories; Kyowa Hakko Kirin Pharma, Inc.

Editorial boards Cancer Prevention Research; Photodermatology, Photoimmunology, & Photomedicine; UpToDate; eMedicine; Journal of Dermatological Sciences; JAMA Dermatology

Leadership positions in professional societies American Academy of Dermatology (Vice Chair, Committee on Science and Research); Photomedicine Society (Board of Directors)