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Background/methods: The treatment of psoriasis with high-dose exposure to oral psoralen and ultraviolet-A light (i.e., PUVA) substantially increases the risk of cutaneous squamous cell cancer, but not of basal cell cancer, within a decade of beginning treatment. To assess the persistence of cancer risk among individuals treated with PUVA, including those who discontinued therapy long ago and those without substantial exposure to other carcinogens, we prospectively studied a cohort of 1380 patients with psoriasis who were first treated during the period from January 1, 1975, through October 1, 1976, and evaluated risk factors associated with the development of cutaneous squamous cell cancers and basal cell cancers after 1985.Results: From 1975 through 1996, 237 patients developed 1422 cutaneous squamous cell cancers. From 1986 through 1996, 135 (12.5%) of 1081 patients without a prior squamous cell cancer developed 593 such tumors. From 1975 through 1997, 247 patients developed 1042 basal cell cancers; these patients included 151 individuals with a first basal cell cancer after 1985. Among those without a squamous cell or a basal cell cancer in the first decade of the prospective study, a strong dose-related increase in the risk of squamous cell cancer was observed in the subsequent decade (adjusted relative risk [> or =337 treatments versus <100 treatments] = 8.6; 95% confidence interval = 4.9-15.2). Risk of basal cell cancer was substantially increased only in those patients exposed to very high levels of PUVA (> or =337 treatments).Conclusions: High-dose exposure to PUVA is associated with a persistent, dose-related increase in the risk of squamous cell cancer, even among patients lacking substantial exposure to other carcinogens and among patients without substantial recent exposure to PUVA. Exposure to PUVA has far less effect on the risk of basal cell cancer. The use of PUVA for psoriasis should be weighed against the increased cancer risk. [ABSTRACT FROM AUTHOR]