Ultraviolet Radiation and Cutaneous Carcinogenesis

Abstract

Nonmelanoma skin cancer (NMSC) is the most common type of human cancer. Solar ultraviolet radiation (UVR) is the main causative factor in the development of NMSC. UVR plays a variety of roles in the induction of skin cancers. It can serve as a complete carcinogen or as a promoter of carcinogenesis. The typical UV-induced DNA damage is the generation of dimeric photoproducts between adjacent pyrimidine bases. Tumor suppressor gene p53 is a common target of UVR-induced mutations. There is a proliferative advantage of p53 mutant keratinocytes over normal keratinocytes that eventuates in neoplastic transformation. While UVB causes considerable DNA damage in the skin, UVA has only recently been shown to induce pyrimidine dimers and oxygen and nitrogen reactive species which damage DNA, proteins and lipids. The immunosuppressive effect of UVR contributes to its carcinogenic activity. Finally, any one of these effects of UVR may contribute to the induction of skin cancers by other agents such as X-rays, viruses, or chemical carcinogens. The mechanism by which UVR leads to cutaneous malignant melanoma is less clear and it may be a cofactor rather than an initiator of this tumor. Primary prevention of UVR exposure is the most effective means of reducing UVR carcinogenesis. Systemic retinoids may influence the appearance of new tumors in patient populations at increased risk of developing NMSC such as xeroderma pigmentosum and organ transplant recipients, but their efficacy is hindered by their side effects.