Non-melanoma Skin Cancer Prevention: Impact of Non-Steroidal Anti-Inflammatory Drugs, Retinoid Dose Response and Measurement Reliability

Abstract

Non-melanoma skin cancers (NMSC) are the most common malignant neoplasms in the White population, afflicting about 20% at some point in life (1, 2). The incidence of NMSC is increasing by two to three percent per year (2). Strategies for NMSC prevention are important because, although NMSC does not result in substantial mortality, it does have the ability to cause substantial morbidity, including disfigurement and loss of function, and treatment is costly (3).The goals of the dissertation were to explore the reliability, clinical, epidemiological, pharmacoepidemiological and statistical issues that potentially affect studies of NMSC prevention. This dissertation utilized three studies designed to examine ways to prevent NMSC recurrence or identify early markers in the development of NMSC (SKICAP-AK trial, n=2,297, SKICAP-SCC/BCC trial, n=525, and Biomarkers 1 Study, n=91). The goals of this research were to examine the impact of non-steroidal anti-inflammatory drugs (NSAIDs) on NMSC recurrence, determine if there was a dose response for treatment with the drugs isotretinoin and retinol on the recurrence of NMSC, and examine factors related to reliability of NMSC risk assessment questionnaires often used in epidemiological and clinical studies.Overall, the findings of this research indicated that NSAIDs likely play a role in reducing the risk of developing an SCC in those at high risk, and that the use of oral isotretinoin and retinol play little role in reducing the risk of redevelopment of NMSC in those who have had a previous NMSC. In addition, there was evidence of substantial reproducibility for factors related to assignment into skin cancer risk group and self-reported history of skin lesions, with self-reported sun sensitivity questions being somewhat less reliable. More research should be done to address the role of NSAIDs in chemoprevention at both the basic science level and epidemiological level. Additional secondary analyses of large data sets that contain information on NMSC and NSAIDs use should be conducted in order to further strengthen the argument that NSAIDs play a role in reducing NMSC occurrence. Future work should focus on determining the specific populations that could benefit from NSAIDs use for the reduction of NMSC.