Cyclooxygenase-2 (COX-2) inhibitor has been associated with lower risk of several cancers, but epidemiological studies on skin cancer risk have been limited and inconclusive. COX-2 inhibitor use and risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma were evaluated in three prospective cohorts - the Nurses’ Health Study (NHS, 2000-2012), NHS II (2001-2011), and the Health Professionals Follow-up Study (HPFS, 2002-2012). COX-2 inhibitor use and skin cancer incidence were assessed using biennial questionnaires, with cSCC and melanoma cases verified by pathological records. A total of 16,098 BCC, 1,973 cSCC, and 625 melanoma cases were documented in these three cohorts. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. After pooling the three cohorts, we found that for ever versus never users, COX-2 inhibitor use was associated with increased BCC risk with multivariable HR 1.10 (95% CI 1.06—1.15). No significant association was found for cSCC or melanoma, although the HRs were similar to that of BCC, with multivariable HR 1.12 (95% CI 0.99—1.26) for cSCC and 1.10 (95% CI 0.89—1.38) for melanoma. COX-2 inhibitor use was associated with modest increased risk of BCC in these cohorts of Caucasian health professionals. Limitations include a homogenous population with restricted generalizability, self-reported use of medications, and relatively short follow-up duration. Further long-term investigation in other populations are needed to replicate these results.

Cyclooxygenase-2 Inhibitor Use and Risk of Skin Cancer: Three Prospective Cohort Studies