Here we review recent insights in the genetics of skin cancer susceptibility as gleaned from studies of three hereditary syndromes: basal cell nevus syndrome, familial melanoma/dysplastic nevus syndrome, and xeroderma pigmentosum. We provide a brief synopsis of the recent findings related to these syndromes in an attempt to illustrate several emerging themes in the genetics of skin cancer. These themes include 1) the recent identification of multiple cancer susceptibility genes that occur in a myriad of cellular regulatory pathways; 2) the relative specificity of certain regulatory pathways to the development of specific types of cancer; and 3) the important role of DNA damage caused by ultraviolet radiation and defective DNA repair mechanisms in the development of skin cancer. We also review the implications of this knowledge to clinical practice relative to risk assessment, primary prevention, and therapy.
