Skip to Main Content


  1. Nonmelanoma skin cancer is the most common malignancy in many Caucasian populations. Approximately 80 percent of the tumors are basal cell carcinomas (BCCs), the majority of the remaining 20 percent being squamous cell carcinomas (SCCs). Putative precursor lesions, such as actinic keratoses, are even more common. Basal cell carcinomas and squamous cell carcinomas are readily diagnosed on the basis of clinical and histopathologic appearance. Basal cell carcinomas rarely metastasize, and although squamous cell carcinomas have a low rate of metastasis, overall case fatality is low. Surgical therapy or radiotherapy is highly effective.

  2. The main environmental cause is ultraviolet radiation, and the major genetic influence is through the major physiologic adaptation to ultraviolet radiation, namely, pigmentation. Studies of coat color in the mouse suggest that over 100 loci are involved in determining pigmentation, and to date, the loci important in accounting for differences in pigmentary characteristics between different human populations are largely unknown. Recently, mutations in the melanocortin 1 receptor (MC1R), a receptor for melanocyte-stimulating hormone, have been shown to be strongly associated with red hair and fair skin.

  3. Familial disorders characterized by a simple Mendelian inheritance pattern probably account for fewer than 1 percent of all cases of skin cancer. The most common disorder is the nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome), an autosomal dominant disorder with an estimated minimum prevalence of 1 in 56,000 in a U.K. population. Nevoid basal cell carcinoma syndrome is characterized by multiple BCCS, a high incidence of other neoplasms including medulloblastomas, ocular abnormalities, and a variety of developmental abnormalities including odontogenic keratocysts. The gene for nevoid basal cell carcinoma syndrome was mapped by several groups to 9q22-31 and has been identified as the human homologue (PTC) of the Drosophila gene patched (ptc). Mutations of PTC have been found in NBCCS probands and in sporadic BCC as well as in a range of central nervous system (CNS) tumors including medulloblastomas, which are a feature of the NBCCS syndrome. Loss of heterozygosity data is compatible with its role as a tumor suppressor, and some developmental anomalies, such as the odontogenic keratocysts, also may fit the two-hit model. The other developmental anomalies suggest a dosage effect. The pattern of expression in the mouse is compatible with its putative role in developmental abnormalities in the human. PTC acts in the Hedgehog signaling pathway so as to inhibit the action of smoothened (SMO); mutations of patched therefore may exert similar effects to activating mutations of smoothened, a model supported by the recent identification of activating mutations of SMO in sporadic BCCs.

  4. There is no inherited syndrome principally characterized by an elevated risk of squamous cell carcinoma (increased rates of SCC and BCC are seen in xeroderma pigmentosum). The Ferguson Smith syndrome (self-healing epitheliomata of Ferguson Smith) is characterized by lesions that clinically and pathologically resemble squamous cell carcinomas but are distinct because they involute spontaneously. On a worldwide basis, the syndrome is extremely rare. The Ferguson Smith syndrome maps to the same locus as the nevoid basal cell carcinoma syndrome. It is not known at present whether the two conditions are allelic or caused by separate genes.

  5. p53 mutations are common in both BCC and SCC. Nonmelanoma skin cancers, however, are not a feature of the Li-Fraumeni syndrome. The mutational spectrum in nonmelanoma skin cancer with frequent C→T and CC→TT transitions strongly supports ultraviolet radiation as the relevant mutagen.

  6. Although BCCs and SCCs show frequent p53 mutations and ras mutations have been described in both tumor types, loss of heterozygosity studies show clear differences between the two tumor types. In BCCs, which usually are diploid, allelic loss is uncommon and is almost entirely confined to the Gorlin locus on 9q. By contrast, in SCC, the fractional allelic loss is 25 to 30 percent, with loss of heterozygosity being common on chromosomes 3, 9, 13, and 17. Loss of heterozygosity studies clearly distinguish SCC from BCC, keratoacanthoma (a regressing form of nonmelanoma skin cancer), and other rarer tumor types, including appendageal tumors.

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.