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Pain Meds Linked to Lower Risk for Skin Cancer


By Charles Bankhead, Staff Writer, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

  • People who used common nonsteroidal anti-inflammatory drugs (NSAIDs) had a significantly lower risk of melanoma and squamous-cell skin cancer (SCC), and the benefit increased with duration and drug dose.
  • Point out that NSAID use was not associated with a reduced risk of basal-cell skin cancer (BCC) overall, but was associated with a reduced risk of BCC at sites other than the head and neck.

People who used common nonsteroidal anti-inflammatory drugs (NSAIDs) had a significantly lower risk of melanoma and squamous-cell skin cancer (SCC), and the benefit increased with duration and drug dose, according to a large Danish cohort study.

Any NSAID use was associated with a 15% reduction in the relative risk of SCC and a 13% lower risk of melanoma. NSAID use had no overall effect on basal-cell skin cancer (BCC), but was associated with a statistically reduced risk of BCC at sites other than the head and neck.

The findings were based on a review of prescriptions and did not include over-the-counter NSAIDs.

“All estimates of reduced risk were driven primarily by the use of nonselective NSAIDs and older COX-2 inhibitors [such as] diclofenac, etodolac, and meloxicam,” Sigrun Alba Johannesdottir, BSc, of Aarhus University Hospital in Denmark, and co-authors wrote in Cancer online.

“Given the high skin cancer incidence and the widespread and frequent use of NSAIDs, a preventive effect of these agents may have important public health implications,” they added.

Multiple studies have suggested that NSAIDs have chemopreventive effects related to inhibition of cyclooxygenase (COX) enzymes, which are anti-apoptotic and immunosuppressive, as well as stimulators of angiogenesis and invasiveness. The chemopreventive benefits have been demonstrated most conclusively for colorectal cancer but may well extend to other types of cancer, the authors wrote.

Results of several studies have implied a protective effect of NSAIDs against keratinocyte carcinomas, including SCC, BCC, and melanoma. Additionally, a single randomized, controlled study showed that users of the COX-2 inhibitor celecoxib (Celebrex) had a reduced risk of keratinocyte carcinomas.

Comparison and extrapolation of previous studies’ results are confounded by variations in outcomes, study design, study populations, and the types and measures of NSAID use, the authors noted.

Using information from a validated database, Johannesdottir and colleagues performed a case-control study from prescription-drug registries encompassing almost 2 million people living in northern Denmark. They identified all residents who had at least a 2-year prescription history spanning the time from 1989 to 2008.

NSAID users were defined as residents who filled more than two prescriptions for NSAIDs or aspirin during the study period. Users were further defined as recent users (more than two prescriptions within 1- or 2-year period prior to skin cancer diagnosis) or former users (more than two prescriptions but not within the specified time period).

Short-term NSAID use was defined as less than 7 years and long-term use as 7 years or longer. The investigators defined intensity of NSAID use as the number of days of prescription coverage divided by the total number of days of use. Low-intensity use was defined as less than 25% and high intensity as 25% or higher.

Anyone who filled two or fewer prescriptions was identified as a nonuser.

Investigators also identified concurrent use of medications that might increase a person’s risk of skin cancer — such as glucocorticoids and immunosuppressants — and comorbid conditions that predispose individuals to an increased cancer risk — such as autoimmune disorders, which also are associated with increased NSAID use. These factors were taken into account during statistical analysis.

Cases of skin cancer were ascertained by data from the Danish national cancer registry.

The authors identified 1,974 patients who developed SCC, 13,316 who developed BCC, and 3,242 who had a history of melanoma. Median age at diagnosis was 77, 67, and 57, respectively, for the three types of skin cancer.

Each cancer case was matched with 10 controls from the same population, resulting in a control group of 178,655 individuals. The control group included 67,338 patients (38%) who met the definition of ever-users of NSAIDs.

The overall analysis showed small, but statistically significant associations between NSAID use and a reduced risk of SCC and melanoma. The magnitude of the associations varied by the duration and intensity of NSAID use.

The risk of SCC was reduced across all durations and intensities of use, including various combinations — such as long-term, high-intensity use. Both long duration and high-intensity use further reduced the risk of melanoma (0.84 and 0.70, respectively).

The combination of high-intensity use for a long duration reduced melanoma risk by 46%. High-intensity use for a long duration reduced SCC risk by 35% and BCC risk by 17%, which achieved statistical significance.

With respect to the type of NSAID use, the authors found that aspirin, nonselective NSAIDs, and COX-2 inhibitors (older and newer) had a similar effect on SCC risk. Similar associations were seen with melanoma, with the exception of no association with newer COX-2 inhibitors.

Stratified analysis showed that the inverse association between NSAIDs and BCC was limited to cancers arising on areas of the body exposed to less ultraviolet radiation. The effects on SCC and melanoma were independent of anatomic site.

A separate analysis of acetaminophen use yielded an unexpected 32% reduction in the risk of BCC at sites other than the head and neck. With respect to melanoma, acetaminophen had no overall effect, but long-duration or high-intensity use was associated with a 20% to 30% risk reduction. Acetaminophen use had no association with SCC.

The main limitation of the study was that skin cancer cases were obtained through a database that only captures an estimate estimated 60% of SCC and BCC cases.

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