Journal of Carcinogenesis & Mutagenesis

Abstract

Epidermal Pigmentation, Nucleotide Excision Repair and Risk of Skin Cancer

Perry Christian, Jillian Vanover, Timothy Scott, Greg Tullo and John A. D’Orazio

As a group, malignancies of the skin are the most commonly diagnosed cancers, with over a million cases each year identified in the United States alone. While the keratinocyte malignancies – basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – represent the majority of clinical cases of skin cancer, malignant melanoma is the most deadly form of skin cancer. Each of these skin malignancies is clearly linked to UV radiation, with chronic cumulative UV exposure being most relevant for keratinocyte malignancies and intense, blistering sunburns most relevant for melanoma. In this review, we describe the epidemiology of skin cancer, the link with UV radiation, and the innate defenses used to resist UV damage with particular attention to the nucleotide excision DNA repair pathway. We also focus on the role of skin pigmentation and the molecular events that control melanization of the skin, since these signaling pathways appear to be major determinants of skin cancer risk. We are particularly interested in the melanocortin 1 receptor (MC1R) signaling pathway which influences basal skin pigmentation, the ability to tan and the efficiency by which UV-induced photolesions are repaired in melanocytes after UV exposure.