Risk of Squamous Cell Carcinoma and Methoxsalen (Psoralen) and UV-A Radiation (PUVA)

Stern, Robert S.; Lunder, Elissa J.

doi:10.1001/archderm.134.12.1582

Cited by 203 publications

(137 citation statements)

References 20 publications

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“…Regarding long-term safety, PUVA has been shown to be a carcinogen and treatment is dose dependently associated with the risk of squamous cell carcinomas. This has been convincingly demonstrated in a large cohort of patients with psoriasis (43). Although similar studies are not available for MF, the pertinent literature indicates that there is also a similar risk in these patients for the development of nonmelanoma skin cancer (60).…”

Section: Puvamentioning

confidence: 85%

Phototherapy of mycosis fungoides

Trautinger

2011

Photoderm Photoimm Photomed

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SummaryBackground/purpose: Among the primary cutaneous T-cell lymphomas, mycosis fungoides (MF) is the most common disease entity. Recently, an improved understanding of the pathology, clinical presentation, and prognosis of MF has lead to the development of new and practically useful classification and staging systems. In most patients, MF presents with patches and plaques and remains confined to the skin for years and decades, making it an ideal target for phototherapy. However, treatment schedules vary widely and this review describes the current knowledge about phototherapy of MF focusing mainly on narrow-and broadband UVB and 8-methoxypsoralen plus UVA, its indications, practical aspects, and clinical outcome. Methods: Review and summary of the pertinent literature. Results and conclusions: Since 1976, when the first report on phototherapy for MF was published, sufficient evidence has accumulated to make narrowband UVB and PUVA safe and effective treatment options for early stages of the disease. In refractory cases or more advanced stages, combination of phototherapy with systemic treatments including mainly interferons and retinoids might be valuable. Additional research is required to further define the optimal treatment schedules and the role of maintenance.

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Section: Puvamentioning

confidence: 85%

Phototherapy of mycosis fungoides

Trautinger

2011

Photoderm Photoimm Photomed

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“…78,87,102,103 An increased risk of SCC has been convincingly demonstrated for psoriasis patients treated with psoralen and ultraviolet A (PUVA). 80,[103][104][105] Treatment with either coal-tar or cyclosporine also increases the risk of SCC development. 80,106,107 Although numerous studies fail to demonstrate an increased risk of melanoma among PUVA-treated psoriasis patients, 80,83,87,91 one group found an increased risk of melanoma among psoriasis patients treated with aggressive PUVA after fifteen years of follow-up.…”

Section: Malignanciesmentioning

confidence: 99%

National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening

Kimball

Gladman

Gelfand

et al. 2008

Journal of the American Academy of Dermatology

381

321

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“…The major products of the first photoreaction step are furan-side monoadducts; these can undergo a second photoreaction at the pyrone side to generate interstrand cross-links. Psoralen plus ultraviolet A (PUVA) therapy is used to treat the skin disorders psoriasis and vitiligo; although effective, this treatment has been found to induce nonmelanoma skin cancers in a dose-dependent manner (12).…”

mentioning

confidence: 99%

Recombinational and Mutagenic Repair of Psoralen Interstrand Cross-links in Saccharomyces cerevisiae

Greenberg

Alberti

Hearst

et al. 2001

Journal of Biological Chemistry

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Psoralen photoreacts with DNA to form interstrand cross-links, which can be repaired by both nonmutagenic nucleotide excision repair and recombinational repair pathways and by mutagenic pathways. In the yeast Saccharomyces cerevisiae, psoralen cross-links are processed by nucleotide excision repair to form double-strand breaks (DSBs). In yeast, DSBs are repaired primarily by homologous recombination, predicting that cross-link and DSB repair should induce similar recombination end points. We compared psoralen cross-link, psoralen monoadduct, and DSB repair using plasmid substrates with site-specific lesions and measured the patterns of gene conversion, crossing over, and targeted mutation. Psoralen cross-links induced both recombination and mutations, whereas DSBs induced only recombination, and monoadducts were neither recombinogenic nor mutagenic. Although the cross-link-and DSB-induced patterns of plasmid integration and gene conversion were similar in most respects, they showed opposite asymmetries in their unidirectional conversion tracts: primarily upstream from the damage site for cross-links but downstream for DSBs. Cross-links induced targeted mutations in 5% of the repaired plasmids; all were base substitutions, primarily T 3 C transitions. The major pathway of psoralen cross-link repair in yeast is error-free and involves the formation of DSB intermediates followed by homologous recombination. A fraction of the cross-links enter an error-prone pathway, resulting in mutations at the damage site.DNA interstrand cross-linkers are used widely in cancer chemotherapy because of their high cytotoxicity in replicating cells (1). These lesions are complex, and their repair involves several different DNA repair pathways. As with other forms of chemical damage, excision repair systems incise the damaged DNA strands; however, there is no undamaged strand to act as a template, and full repair requires the participation of additional pathways. Recombinational repair pathways are involved in restoring the intact duplex structure after excision (2-7). Additionally, cross-links efficiently induce mutations, implicating error-prone pathways in their repair (8,9).Psoralens are photoreactive DNA cross-linking agents that react with pyrimidine bases on opposite DNA strands in the presence of near ultraviolet light; 5Ј-TpA-3Ј sequences are preferred cross-linking sites (10, 11). There are two photoreactive positions in the psoralen molecule, the 4Ј,5Ј furan and the 3,4 pyrone double bonds, which can undergo sequential photoreactions to form cross-links. The major products of the first photoreaction step are furan-side monoadducts; these can undergo a second photoreaction at the pyrone side to generate interstrand cross-links. Psoralen plus ultraviolet A (PUVA) therapy is used to treat the skin disorders psoriasis and vitiligo; although effective, this treatment has been found to induce nonmelanoma skin cancers in a dose-dependent manner (12).Both nucleotide excision repair (NER) 1 and recombinational repair pathways partic...

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Risk of Squamous Cell Carcinoma and Methoxsalen (Psoralen) and UV-A Radiation (PUVA)

Cited by 203 publications

References 20 publications

Phototherapy of mycosis fungoides

Phototherapy of mycosis fungoides

National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening

Recombinational and Mutagenic Repair of Psoralen Interstrand Cross-links in Saccharomyces cerevisiae

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