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.