Cutaneous melanoma: family screening and genetic testing

The incidence of cutaneous melanoma (CM) has been steadily increasing in recent decades. Ultraviolet radiation (UVR) exposure, in the form of intermittent heavy exposure and severe sunburns in childhood, is believed to be the most important environmental contribution to CM risk. Genetic determinants also modulate CM risk, probably to a greater extent than environmental exposure. Certain heritable traits such as prominent numbers of common and atypical melanocytic nevi, skin type, dense UVR-induced freckling, and hair color are all known to be associated with increased CM risk. Very rarely, a heritable mutation in a high-risk gene renders the susceptible individual at extreme risk for CM. Families may carry one or more of the other high-risk phenotypic traits leading to uncertainty about how to quantify CM risk and provide management recommendations. Commercial genetic testing for the known high-risk inherited genetic mutations is available but is only relevant for those rare families likely to be carrying identifiable mutations. CM screening and risk intervention programs are being established internationally for families at markedly increased risk. Algorithms based on the level of risk are proposed.