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Nataraj, AJ; Wolf, P; Cerroni, L; Ananthaswamy, HN.
p53 mutation in squamous cell carcinomas from psoriasis patients treated with psoralen + UVA (PUVA).
J Invest Dermatol. 1997; 109(2):238-243 Doi: 10.1111%2F1523-1747.ep12319764 [OPEN ACCESS]
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Co-authors Med Uni Graz
Cerroni Lorenzo
Wolf Peter
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Abstract:
Individuals suffering from psoriasis are treated with a combination of psoralen and UVA radiation, commonly referred to as "PUVA" therapy. Epidemiologic studies have shown that PUVA therapy is a risk factor for skin cancer in psoriasis patients. Although PUVA treatment induces skin cancer in laboratory animals, it is unknown whether the increased incidence of skin cancer reported in PUVA-treated psoriasis patients is due to the carcinogenic effects of PUVA or due to other factors such as UVB. Because UV and PUVA induce different types of DNA damage resulting in unique types of p53 mutation, we investigated whether skin cancers from PUVA-treated psoriasis patients have PUVA-type or UV-type p53 mutations. Analysis of 17 squamous cell carcinomas (SCCs) from Austrian PUVA-treated patients revealed a total of 25 p53 mutations in 11 SCCs. A majority of p53 mutations occurred at 5'TpG sites. Although previous studies have shown that 5'TpA sites are the primary targets for PUVA mutagenesis, substitutions at 5'TpG sites are also quite common. Interestingly, a sizable portion of p53 mutations detected were C-->T or CC-->TT transitions, characteristic of UV-induced mutations. Because some psoriasis patients had substantial exposure to UVB before PUVA therapy and because the light sources used in PUVA therapy contained small but significant wavelengths in the UVB region, it is possible that the C-->T and CC-->TT transitions detected in SCCs from PUVA-treated patients were induced by UVB. Nonetheless, our results indicate that both PUVA and UVB may play a role in the development of skin cancer in Austrian psoriasis patients who undergo PUVA therapy.
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Carcinoma, Squamous Cell - etiology
Female - etiology
Genes, p53 - genetics
Humans - genetics
Male - genetics
Middle Aged - genetics
Mutation - radiation effects
PUVA Therapy - adverse effects
Polymorphism, Single-Stranded Conformational - adverse effects
Psoriasis - therapy
Skin Neoplasms - etiology

Find related publications in this database (Keywords)
Carcinogenesis
Mutagenesis
Skin Cancer
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