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p53 mutation in nonmelanoma skin cancers occurring in psoralen ultraviolet a-treated patients: evidence for heterogeneity and field cancerization.

Abstract
A combination of psoralens and ultraviolet A radiation is widely used to treat psoriasis. Long-term, high-dose exposure to psoralen + ultraviolet A is associated with an increased risk of nonmelanoma skin cancer, particularly squamous cell carcinoma. In this study, we used p53 mutations as a molecular marker to determine the separate contributions of psoralen + ultraviolet A and other ultraviolet exposures, such as ultraviolet B for skin cancer development in psoralen + ultraviolet A-treated psoriasis patients. The results indicated that of 69 tumors analyzed, 37 (54%) tumors had one or more p53 mutations. Of 37 tumors with mutations, 17 (46%) tumors had only ultraviolet-type mutations, two (5%) tumors had only psoralen + ultraviolet A-type mutations, and 18 (49%) tumors had both types of mutations. Interestingly, psoralen + ultraviolet A-type p53 mutations were more frequent than ultraviolet type in tumors arising in patients with high-dose exposure to psoralen + ultraviolet A. Field cancerization and tumor heterogeneity appeared to occur frequently in the same patient and even in the same tumor. This study's data suggest that psoralen + ultraviolet A-induced p53 mutations may play an important part in the development of nonmelanoma skin cancer in psoralen + ultraviolet A-treated patients, but these mutations are likely to act in concert with the effects of other carcinogenic exposures, particularly ultraviolet B, in the development of skin cancer.
AuthorsRobert S Stern, Svetlana Bolshakov, Arun J Nataraj, Honnavara N Ananthaswamy
JournalThe Journal of investigative dermatology (J Invest Dermatol) Vol. 119 Issue 2 Pg. 522-6 (Aug 2002) ISSN: 0022-202X [Print] United States
PMID12190879 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Topics
  • Adult
  • Aged
  • Female
  • Genes, p53
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • PUVA Therapy (adverse effects)
  • Skin Neoplasms (etiology, genetics)

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