NSAIDS and Skin Cancer: Reduced Risk?

Jeannette Y. Wick, RPh, MBA, FASCP
Published Online: Monday, January 21, 2013
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A pair of studies that aimed to determine whether nonsteroidal anti-inflammatory drugs can reduce the risk of skin cancer have produced conflicting results.

Numerous studies have been conducted to determine whether nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a decreased risk of cancer. The proposed mechanisms include cyclooxygenase inhibitions leading to decreased apoptosis, immunosuppression, or changes in angiogenesis and the ability to invade normal tissue.
 
Most research has focused on colorectal cancer, but squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM) are also of interest. SCC is closely associated with actinic keratosis, whereas BCC and MM are more closely linked to sun exposure and skin damage.
 
In an attempt to establish a link between NSAID use and a reduced risk of skin cancer, Danish researchers gathered prescription data covering 2 years for approximately 1.8 million people. The NSAID categories they included were aspirin, nonselective non-aspirin NSAIDs, and COX-2 inhibitors.
 
The results, published in the October 1, 2012, edition of Cancer, indicated that NSAID use was associated with a decreased risk of skin cancer, particularly SCC and MM. Patients were more likely to have a decreased risk after greater duration and intensity of use. Older COX-2 inhibitors (including diclofenac) were more likely to reduce risk of SCC than BCC and MM.
 
The difference in risk levels may be due to dissimilarities in COX enzyme expression in different skin types. The authors note that elevated COX-2 levels are more likely to occur in SCC and its precursor lesions (eg, actinic keratosis and Bowen disease). This is not the case with BCC and MM. They also suggest that some NSAIDs have phototoxic effects that increase the likelihood of sunburn and subsequently increase the risk of developing MM and BC. This increased chance of sunburn may negate any protective effect the NSAIDs may confer.
 
Prescribed acetaminophen was used as a comparison product since acetaminophen is used for comparable indications to NSAIDs, but works through a different molecular mechanism. Surprisingly, they found that acetaminophen decreased the risk of BCC and MM, but not SCC.
 
The study had several limitations, including a reliance on data indicating that medications were dispensed (with no verification that they were taken as prescribed) and the possibility that patients in the control group may have taken OTC NSAIDs. The study also did not take into account lifestyle factors, most importantly sun exposure.
 
The Nurses’ Health Study has tracked aspirin use prospectively since 1980 and other NSAID use since 1990. It also collects data on hair color and sunburns. Researchers working on the study recently analyzed data from 92,125 participants to determine whether aspirin or non-aspirin NSAIDs help protect against melanoma or non-melanoma skin cancers.
 
Their results, published in the September 2012 edition of Cancer Causes & Control, indicated that neither aspirin nor non-aspirin NSAID use was associated with a significantly lower risk of SCC, BCC, or MM, even among women with high quantity, frequency, or duration of use. In aspirin users, the risk of melanoma was elevated, and the risk of SCC was mildly decreased. Risk of SCC appeared to be reduced in acetaminophen users.
 
Several randomized studies designed to further assess the role of NSAIDs in chemoprevention of cancer are currently underway.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.

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