Malignant melanoma of the skin is the leading cause of death from
skin cancer and ranks fifth in
cancer incidence among all
cancers in the United States. While
melanoma mortality has remained steady for the past several decades,
melanoma incidence has been increasing, particularly among fair-skinned individuals. According to the American Cancer Society, nearly 10,000 people in the United States will die from
melanoma this year. Individuals with dark skin complexion are protected damage generated by UV-light due to the high content of UV-blocking
melanin pigment in their epidermis as well as better capacity for melanocytes to cope with UV damage. There is now ample evidence that suggests that the
melanocortin 1 receptor (MC1R) is a major
melanoma risk factor. Inherited loss-of-function mutations in MC1R are common in
melanoma-prone persons, correlating with a less melanized skin complexion and poorer recovery from mutagenic photodamage. We and others are interested in the MC1R signaling pathway in melanocytes, its mechanisms of enhancing
genomic stability and pharmacologic opportunities to reduce
melanoma risk based on those insights. In this chapter, we review
melanoma risk factors, the MC1R signaling pathway, and the relationship between MC1R signaling and DNA repair.