NSAID Exposure Not Linked to Cutaneous Small-Cell Carcinoma Risk

Laurie Barclay, MD

February 19, 2010

February 19, 2010 — Neither self-reported nor pharmacy-dispensed nonsteroidal anti-inflammatory drug (NSAID) exposure was associated with cutaneous small-cell carcinoma (SCC) risk, according to the results of a retrospective case-control study reported online February 15 in the Archives of Dermatology.

"In addition to their anti-inflammatory properties, NSAIDs also inhibit neoplastic proliferation by inducing apoptosis and inhibiting angiogenesis," write Maryam M. Asgari, MD, MPH, from Kaiser Permanente Northern California (KPNC) in Oakland, and colleagues. "Epidemiologic studies and randomized trials have shown protective effects of NSAIDs for several cancers including colorectal, breast, prostate, and lung. Laboratory studies suggest that NSAIDs exert protective effects against cutaneous [SCCs] both in vitro and in animal models. However, few epidemiologic studies have examined the association between NSAID use and SCC risk, and these have yielded conflicting information."

At KPNC, a large, population-based, health maintenance organization, a random sample of 415 KPNC members diagnosed as having a pathologically verified SCC in 2004 were matched by age, sex, and race to 415 control patients with no history of skin cancer. The primary measure of exposure was self-reported NSAID use in the 10-year period preceding baseline, categorized by type (any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs).

To estimate the association of SCC with regular use, dose, and duration of exposure to different types of NSAID, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. In addition, the investigators also reviewed data on pharmacy-dispensed NSAIDs to evaluate the association of this exposure with SCC risk. A fully adjusted model allowed adjustment for all ascertained SCC risk factors, and a parsimonious model allowed adjustment for only those variables associated with both SCC risk and NSAID use.

Regular use of NSAIDs within the previous 10 years was reported by 61% of participants, including 48% who used aspirin, 18% who used ibuprofen, 5% who used naproxen, and 4% who used nabumetone.

In fully adjusted analyses, there was no statistically significant reduction in SCC risk with self-reported regular use of any NSAID (OR, 1.32; 95% CI, 0.92 - 1.89), aspirin (OR, 1.38; 95% CI, 0.96 - 1.97), ibuprofen (OR, 0.74; 95% CI, 0.46 - 1.19), or nonaspirin NSAIDs (OR, 0.84; 95% CI, 0.56 - 1.26). The findings were not significantly different in analyses looking at duration, dose, and variables combining duration and dose of NSAID exposure, nor in an analysis using the parsimonious model. Using the data on pharmacy-dispensed NSAIDs also showed no association of this exposure with SCC risk.

"Neither self-reported nor pharmacy-dispensed NSAID exposure was associated with cutaneous SCC risk," the study authors write. "Although NSAID users whose exposure was of short duration (1 to 3 years) appeared to be at somewhat increased risk for squamous cell carcinoma, we found no consistent effects of duration of use of any NSAID on [SCC] risk."

Potential limitations of this study include possible recall bias affecting self-reported variables, selection bias, and limited generalizability because only KPNC members were studied.

"We did not detect any consistent relationships between SCC risk and overall NSAID, aspirin, ibuprofen, or nonaspirin NSAID use," the study authors conclude. "Dose and duration of NSAID use did not appear to alter risk of SCC. Given the potential toxic effects of NSAIDs, including platelet dysfunction and gastric ulcers, more uniformly efficacious chemopreventive agents with safer adverse effect profiles need to be explored."

Grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases and from the National Cancer Institute supported this study. One of the study authors served on an advisory committee to Roche Laboratories in June 2008, and in the past 3 years has consulted for law firms serving both plaintiffs and Ortho-McNeil-Janssen Pharmaceuticals regarding litigation concerning celecoxib and Ortho-Evra, respectively. These consultancies had no relationship with or influence on the present study.

Arch Dermatol. Published online February 15, 2010.

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