Ultraviolet Light as a Modulator of Melanoma Development

Abstract

Epidemiological evidence is overwhelming that exposure of the skin to ultraviolet radiation (UVR) can increase one’s risk of developing malignant melanoma. However the situation is complex, as melanoma development is associated with “intermittent” sun exposure, whereas epidermal keratinocyte-based skin cancers like squamous cell carcinoma (SCC) are associated with chronic UVR exposure. Thus it is difficult to talk in terms of a classical UVR carcinogenic mechanism for melanoma in general. Melanoma risk seems intricately associated with pigmentation characteristics. Genome wide association studies identify variants in genes involved in pigmentation as risk factors, generally the strongest signal being for the melanocortin receptor 1 gene (MC1R). One reason postulated to explain the odd relationship between UVR exposure and tumorigenesis is that there may be a unique carcinogenic mechanisms at play involving UVA, that is a weak carcinogen for skin cancer in general. Evidence for UVA causality in melanoma comes from some epidemiological studies, and to some extent from work with animal models. On the other hand, one can argue that there may not be a unique carcinogenic mechanism for melanoma, and that there are several factors that may help explain the apparent difference from typical mechanism of UVR mutagenesis involving classical UVR mutations. Firstly, in terms of normal cellular function, melanocytes principal function is to produce melanin pigment while epidermal keratinocytes are programmed to proliferate and then die as they generate and maintain the epidermis, a barrier for internal tissues and organs. Secondly, there may be genetic differences between individuals developing particular subtypes of melanoma and/or form of sun exposure. Thus particularly relates to susceptibility to naevus development, a critical factor associated melanoma development on the trunk, a site presumably receiving mainly “intermittent” sun exposure.