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.