Cumulative UV Exposure or a Modified SCINEXA™-Skin Aging Score Do Not Play a Substantial Role in Predicting the Risk of Developing Keratinocyte Cancers after Solid Organ Transplantation—A Case Control Study

SIMPLE SUMMARY: Due to life-long immunosuppression, organ transplant recipients are prone to skin cancer development. We evaluated the association of cumulative UV burden with skin aging and skin cancer in two groups of transplant patients with and without skin cancer, who were matched for gender, age, type of organ transplanted, post-transplantation period, and immunosuppressive therapy. Individuals with actinic keratoses had a 7.5-fold risk for skin cancer development, and those with green or blue eyes a 4.1- or 3.6-fold risk, respectively; carriers of particular MC1R genotypes associated with a diminished function had a 1.9-fold increased risk. The extent of skin aging was only connected with a higher number of tumors, but not with the development of skin cancer per se. ABSTRACT: The risk of keratinocyte cancer is determined by intrinsic and extrinsic factors, which also influence skin aging. Few studies have linked skin aging and UV exposure with the incidence of non-melanoma skin cancer (NMSC). We evaluated signs of actinic skin damage and aging, individual UV burden, and melanocortin-1 receptor (MC1R) variants. A total of 194 organ transplant recipients (OTR) who suffered from NMSC were compared to 194 tumor-free controls matched for gender, age, type of transplanted organ, post-transplantation (TX) period, and immunosuppressive therapy. Compared with the cases, the controls scored higher in all skin aging scores and there were no differences in UV burden except for intentional whole-body UV exposure for specific UV scenarios and periods of life in favor of cases. The number of NMSCs correlated with all types of skin aging scores, the extent of intentional sun exposure, older age, longer post-TX period, shorter interval from TX to first NMSC, and specific MC1R risk groups. Multivariable models revealed a 7.5-fold risk of developing NMSC in individuals with actinic keratosis; 4.1- or 3.6-fold in those with green or blue eyes, respectively; and a 1.9-fold increased risk in the MC1R medium- + high-risk group. In the absence of skin aging contributing to NMSC development, certain MC1R risk types may identify OTR at risk for high tumor burden.