May 29, 2012 — Use of nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the risk for developing squamous cell carcinoma (SCC) or malignant melanoma (MM), according to a new population-based, case-control study published online May 29 in Cancer.
Use of NSAIDs overall (>2 prescriptions) was associated with a decreased risk for SCC (incidence rate ratio [IRR], 0.85; 95% confidence interval [CI], 0.76 - 0.94) and MM (IRR, 0.87; 95% CI, 0.80 - 0.95) compared with nonuse (≤2 prescriptions). This was especially true for long-term use (≥7 years) and high-intensity use (>25% prescription coverage during the total duration of use). Although NSAID use was not associated with a reduced risk for basal cell carcinoma (BCC) overall (IRR, 0.97; 95% CI, 0.93 - 1.01), a reduced risk for BCC at sites other than the head was noted with long-term use (IRR, 0.85; 95% CI, 0.76 - 0.95) and high-intensity use (IRR, 0.79; 95% CI, 0.69 - 0.91).
"The effect [of NSAIDs] increased with greater duration and intensity of use, which may reflect a cumulative biologic effect (ie, a dose-response effect) exerted in the initiation of carcinogenesis," write Sigrun Alba Johannesdottir, BSc, from the Department of Clinical Epidemiology, Aarhus University Hospital, Denmark, and colleagues.
The researchers note that the NSAIDs associated with reduced risk were primarily nonselective NSAIDs and older cyclooxygenase (COX)-2 inhibitors (diclofenac, etodolac, and meloxicam). Unlike other studies, "[o]ur results do not support an association between newer COX-2 inhibitors and skin cancer or NSAIDs overall and BCC. However, our findings are in accordance with studies conducted in the general population. Thus, the effects of NSAIDs may depend on the baseline risk of skin cancer," the authors write.
Using the Danish Cancer Registry (DCR), the authors identified all cases of SCC, MM, and BCC diagnosed in individuals 20 years of age or older in northern Denmark from 1991 through 2009. The researchers identified 1974 diagnoses of SCC, 13,316 diagnoses of BCC, and 3242 diagnoses MM.
Information on the site of the cancer was collected, and patients with a history of disorders known to increase the risk for skin cancer (HIV, a previous cancer diagnosis, or history of solid organ transplantation) were excluded.
The investigators used the Danish Civil Registry System to match 10 population control individuals to each case patient based on age, sex, and country of residence. They also used the system to collect information regarding NSAID use. Patients with a history of rheumatoid arthritis, migraines, or cardiovascular disease were identified and these diseases used as proxy measures for chronic NSAID use.
The median age of patients at the time of diagnosis was 77 years, 67 years, and 57 years for SCC, BCC, and MM, respectively. Patients diagnosed with SCC were predominately men (63%), with tumors frequently located on the head and neck (56%). Men accounted for 50% of patients diagnosed with BCC and 45% of patients diagnosed with MM.
The authors acknowledge that analysis of newer COX-2 inhibitors was curtailed by the fact that they were only available during part of the study period and, in some instances, were withdrawn from the market. Results may also have been biased because only 60% of SCC and BCC cases are recorded in the DCR. In addition, the study relied on dispensed prescriptions, which may not accurately reflect actual drug use both among prescription and over-the-counter NSAID users. The authors note, however, that repeated refills for the same medications likely implies adherence to a prescribed treatment regime.
"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," the authors note.
"We observed that NSAIDs overall, including aspirin, other nonselective NSAIDs, and older COX-2 inhibitors, were associated with a decreased risk of skin cancer, particularly SCC and MM," they conclude.
Funding for this study was provided by the Clinical Epidemiological Research Foundation. The authors have disclosed no relevant financial relationships.
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