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  • Skin cancer is quickly becoming a major public health concern. In the United States alone, melanoma has become the fifth and sixth most common cancer in men and women, respectively.

  • Ultraviolet (UV) radiation plays a significant role in the development of skin cancer; however, many genes have been implicated in familial skin cancer development.

  • In familial melanoma, mutations in the CDKN2A gene are found in the majority of high-density melanoma-prone families.


  • The risk of cutaneous malignant melanoma (CMM) among CDKN2A mutation carriers increases with age. By age 80, these individuals’ risk of developing melanoma is as high as 91% in Australia.

  • Besides CMM, mutations in CDKN2A are associated with an increased risk and development of many nonmelanoma cancers, with pancreatic cancer being the most extensively documented associated malignancy.


  • If there is suspicion for familial malignant melanoma, all nevi should be carefully examined in both the patient and the patient’s first- and second-degree relatives. When evaluating these patients, clinicians should pay careful attention to the age at which CMM (and other cancers) has been diagnosed in family members.


  • In families affected by CDKN2A mutations, the age of onset of CMM is much lower than that of the general population. Therefore, family members should be counseled on the importance of sun avoidance and annual skin examinations, beginning at an early age.


The incidence of skin cancer is increasing, and it is quickly becoming a major public health concern. Because basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma are all associated with ultraviolet (UV) radiation exposure, preventive efforts have traditionally been placed on reducing such exposure. However, basic phenotypic traits that are genetically determined, such as hair color, eye color, tanning ability, tendency to burn, and nevus count, are well correlated to skin cancer risk. Therefore, over the years, much has been learned regarding the significant underlying role that genetics plays in the development of skin cancer, both inherited as germline variants and those acquired within tumor development as somatic changes. This chapter will discuss the important genes associated with both the hereditary and sporadic forms of cutaneous malignant melanoma (CMM), cutaneous squamous cell carcinoma (cSCC), and BCC.


Melanoma is a potentially fatal malignancy of the pigment-producing cells (melanocytes) of the skin. The incidence of melanoma continues to increase throughout the world. As such, in the United States, melanoma has become the fifth and sixth most common cancer in men and women, respectively.1 Although melanoma occurs less frequently than squamous cell or basal cell carcinoma, it is responsible for over 75% of deaths related to skin cancer.2 In Australia and New Zealand, melanoma is the most common cause of cancer-related death in young adults.3 Exposure to UV radiation is a well-known and ...

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