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Genetics of Skin Cancer (PDQ®)

Changes to This Summary (01/27/2015)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Basal Cell Carcinoma

Added text to state that evidence from in vivo models indicates that arsenic, alone or in combination with itraconazole, can inhibit the hedgehog pathway in cells with wild-type or mutated Smoothened (cited Kim et al. and Beauchamp et al. as references 26 and 27, respectively). Also added text to state that the effect of arsenic on skin cancer risk may be modified by certain variants in nucleotide excision repair genes (xeroderma pigmentosum types A and D) (cited Applebaum as reference 28).

Added text about a study that analyzed the rate of PTCH1 mutations in basal cell nevus syndrome–associated keratocystic odontogenic tumors (KCOTs) and found that 11 of 17 individuals carried a germline PTCH1 mutation and an additional 3 individuals had somatic mutations in this gene (cited Guo et al. as reference 114). Also added text to state that individuals with germline PTCH1 mutations had an early age of KCOT presentation.

Squamous Cell Carcinoma (SCC)

Added text to state that there are numerous syndromes that lead to epidermolysis bullosa (EB), which is characterized by cleavage and blistering of the skin. A few EB syndromes are associated with an increased risk of skin cancer, particularly SCC (cited Fine et al. as reference 107).


Added text to state that the American College of Medical Genetics and the National Society of Genetic Counselors recommend that an individual with any of the following characteristics be referred for a cancer genetics consultation: a personal history of three or more primary melanomas; a personal history of melanoma and pancreatic cancer; a personal history of melanoma and astrocytoma; three or more cases of melanoma and/or pancreatic cancer in first-degree relatives (FDRs); and melanoma and astrocytoma in two FDRs (cited Hampel et al. as reference 65).

Added text about a study that reported a melanoma incidence rate of 9.9 per 1,000 person years among 354 FDRs and 2.1 per 1,000 person years among 391 second-degree relatives of probands with a p16-Leiden CDKN2A mutation (cited van der Rhee et al. as reference 89).

Added text about a Spanish study of the FDRs of 66 melanoma patients with known pathogenic CDKN2A mutations that showed an increase in other cancers, including pancreatic, lung, and breast (cited Potrony et al. as reference 93).

Revised text to state that population-based studies in Australia and the United Kingdom consisting of 3,920 cases and 4,036 controls show a twofold increased risk of melanoma in carriers of the E318K variant of MITF. Also added text to state that these data remain controversial; subsequent studies in a Polish population of 4,266 cancer patients and 2,114 controls found no association with melanoma (cited Gromowski et al. as reference 165).

Added text to state that professional organizations have published genetic counseling referral guidelines for individuals with a history of melanoma.

Revised text to state that high-risk individuals, including first- and second-degree family members in melanoma-prone families, should be educated about sun safety and warning signs of melanoma.

This summary is written and maintained by the PDQ Cancer Genetics Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.

  • Updated: January 27, 2015