Role of MC1R variants in childhood and adolescent melanoma

Cutaneous melanoma (CM) is rare in children, representing 1-3% of all paediatric malignancies and occurring at a frequency of 0.3-0.4% before puberty. MC1R is a key gene for skin pigmentation and is highly polymorphic in Caucasians. MC1R gene variants are associated with CM in different populations, and with congenital melanocytic naevi in children. The aim of this study is to evaluate whether the prevalence of MC1R variants differed among sporadic childhood and adolescent CM cases compared to adult patients. Data were gathered through the M-SKIP project, an international pooled-analysis on MC1R variants, skin cancer and phenotypic characteristics. CM cases with information on age at diagnosis were selected from the M-SKIP dataset and divided into three groups: childhood (age <=14 years, N=13), adolescent (age 15 to 18 years, N=52) and adult (age > 18 years, N=7,696). The frequency of carrying specific MC1R variants as well as at least one MC1R variant were compared between childhood/adolescent and adult CM cases with Chi Square test. The prevalence of any MC1R variant was lower in children (<=14 years, 63%) than in adolescents (15-18 years, 71%) or adults (>18 years, 75%), although overall the difference was not statistically significant. A higher prevalence of the MC1R V92M variant was found in childhood and adolescent compared to adult CM cases (23% vs 5%, p=0.06). In contrast, the MC1R R151C variant was found less frequently in childhood and adolescent than in adult cases (9% vs 18%, p=0.06). Looking at rare variants in 5,983 cases with MC1R sequenced, 3 (9%) carriers of MC1R ins86A were found among 32 childhood and adolescent patients, while only 44 (1%) carriers of the same variant were found among 5,951 adult cases (p<0.0001). MC1R variants ins86A and V92M, but not R151C, may be specifically associated with childhood and adolescent melanoma. Further studies using a larger sample size is needed to validate the present findings.