Malignant melanoma: another risk reduced by NSAIDs?
Epidemiologists at Ohio State University have reported several analyses demonstrating that regular use of NSAIDs is associated with a reduced risk of certain tumours, notably cancers of the breast, lung and prostate. Using a case-control design, the Ohio investigators have also explored the factors that may contribute to the development of melanoma (Oncol Rep 2001;8:655-7).

They identified 110 middle-aged women with melanoma among patients attending cancer centres in New York and Ohio . They compared sun exposure and use of NSAIDs by each woman to that of six controls without melanoma matched for age, race and place of residence.

As expected, they found that melanoma was associated with increased episodes of sunburn before age 21 (3.2 in cases vs. 1.6 in controls; p<0.01) and current sun exposure (10.6 vs. 6.2 hours/week; p<0.01). Perhaps more surprisingly, regular NSAID use was associated with a 55% lower risk of melanoma: compared with no NSAID use, the odds ratio for melanoma in women who took at least one dose of an NSAID per day for at least 2 years was 0.45 (CI95% 0.22, 0.92). The odds ratios for daily use of OTC ibuprofen (0.42) and aspirin (0.55) were not statistically significantly different but paracetamol was not associated with a reduction in risk (OR 0.95; CI95% 0.45, 1.98).

There was also evidence of a dose-response relationship, with greater NSAID use associated with decreasing risk. Adjustment for sun exposure or age did not alter the risk reductions.

Observational studies such as this do not prove that NSAIDs cause the reduced risk of melanoma. However, the association is strengthened by the dose-response relationship and a plausible hypothesis for the mechanism of action. The enzyme COX-2 is induced by exposure of human skin cancer cells to UV B and is inhibited by NSAIDs such as ibuprofen. The fact that paracetamol, which does not inhibit COX peripherally, had no apparent effect lends further support to a central role for COX-2.

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