Genetic epidemiology of malignant melanoma susceptibility

Germline CDKN2A mutations were the first to be associated with familial melanoma. MC1R polymorphisms are associated, in conformity with epidemiological observations, with fair skin phenotype and a moderately increased risk for melanoma. The wider implementation of genome-wide association studies along with improved whole exome sequencing techniques made possible the identification of novel high-penetrant mutations (TERT, MITF, POT1, BAP1) beyond the established pathways of pigmentation and nevus count suggesting an additional role for pathways involved in cell cycle control and DNA repair. A multitude of common polymorphisms in the general population have been associated through candidate gene studies with a low risk for melanoma, supporting the hypothesis of a complex disease.