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  • Genetic syndromes that increase the risk for the development of nonmelanoma skin cancer include xeroderma pigmentosum, oculocutaneous albinism, Muir-Torre syndrome, epidermodysplasia verruciformis, Gorlin syndrome, Bazex-Dupré-Christol syndrome, Rombo syndrome, and recessive dystrophic epidermolysis bullosa.

  • Genes that are implicated in increasing the risk for melanoma include CDKN2A, CDK4, MITF, Shelterin complex genes, and TERT.

  • Other genes and genetic syndromes that may contribute to an increased risk of melanoma include BAP1, BRCA1/2, Li-Fraumeni syndrome, Cowden syndrome, and retinoblastoma.


  • Although normally slow-growing, nonmelanoma skin cancers affecting individuals with a hereditary predisposition can significantly increase mortality.

  • CDKN2A and CDK4 are the only two genes recommended for genetic screening of a melanoma syndrome.


  • Consider a genetic syndrome in individuals who are young or in those with unusually high numbers of skin cancers.

  • In areas of moderate to severe incidence of melanoma, genetic testing should be performed in individuals with three or more primary melanomas or in families with at least one invasive melanoma and two or more other diagnoses of melanoma or pancreatic cancer.

  • In areas with a low incidence of melanoma, two melanoma diagnoses in a family can warrant genetic testing.


  • Patients should make an appointment with a genetic counselor to ensure that they receive appropriate follow-up for other extracutaneous manifestations and to identify at-risk family members.

  • It is crucial that patients be educated on strict sun protection, including but not limited to: daily sunscreen use, wearing protective clothing such as wide-brimmed hats and ultraviolet protective factor (UPF)-labeled long-sleeved shirts, seeking shade during peak sunlight hours, and avoiding the use of medications that increase photosensitivity.


Worldwide, between 2 to 3 million nonmelanoma skin cancers (NMSCs) and 132,000 melanomas are diagnosed each year.1 Skin cancers result from complex interactions between environmental factors and genetic makeup. It is a common notion that skin cancer can result from prolonged sun exposure and ultraviolet radiation. Additional risk factors for skin cancer include immunosuppression, viral infections, and radiotherapy.2

However, there is a population, albeit small, whose genetics directly predispose them to the development of skin cancer. In this chapter, we will first review the genodermatoses that are associated with the development of NMSC. Next, we will review genes that play a role in hereditary melanoma.


NMSC represents the most common cancer worldwide.3 Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) tend to be slow-growing and rarely metastasize. However, the development of NMSCs in individuals affected by the genodermatoses discussed in this chapter can significantly increase mortality. Table 33-1 summarizes the genodermatoses associated with NMSC.

TABLE 33-1Genodermatoses Associated with Nonmelanoma Skin Cancers

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