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

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.

Identification of Genetic Risk Factors for Keratinocyte Cancer in Immunosuppressed Solid Organ Transplant Recipients: A Case-Control Study

“…Mutations in the MC1R gene are known to lead to decreased eumelanin production, which impairs UV protection and thus increases susceptibility to skin cancer [ 27 , 28 ]. This association with multiple KCs confirms our previous finding that carriers of specific MC1R variants had a higher number of KCs even in individuals with darker skin types, suggesting a pigmentation-independent effect of MC1R variants [ 5 ].…”

“…Furthermore, genome-wide association studies (GWAS) have identified specific genetic loci associated with KC susceptibility. These loci are connected to genes involved in keratinocyte differentiation, cancer development and progression, DNA damage repair, immune regulation, and pigmentation [ 1 , 3 , 4 , 5 , 6 , 7 , 8 , 77 ].…”

“…Our aim was to understand genetic factors that increase KC risk and thus explain KC development, which was not clarified by our previous studies in this patient cohort [5].…”

“…Skin aging, UV-related skin damage, or cumulative UV exposure could not explain KC development. Only holiday-related high-intensity UV exposure, specific MC1R variants, and the presence of actinic keratosis (AK) increased the risk for KC [ 5 ]. Thus, we think, that additional, probably genetic, factors may predispose to the development of KC in this thoroughly characterized population of SOTR.…”

“…Our aim was to understand genetic factors that increase KC risk and thus explain KC development, which was not clarified by our previous studies in this patient cohort [ 5 ]. To achieve this, we evaluated the contribution of common variants on the one hand and rare variants on the other hand.…”