UV or not UV: metals are the answer.

Advances in our understanding of the etiology of cutaneous melanoma over the past decade have implicated constitutive heredity alterations in a small percentage of cases (5-8%). Using the power of competitive genomic hybridization, melanomas located in intermittently sun exposed areas have been associated with BRAF abnormalities whereas those located in chronic sun-exposed areas have not shown such an association (1). A large number of abnormalities in many signaling pathways have been described by us and others in melanoma (2, 3) although the genetic basis per se for most of these alterations is unknown. Squamous cell cutaneous cancer is strongly associated with lifetime cumulative sunlight exposure, and classic UV light mutations are consistently detectable nearby and within the malignancy (4). In contrast, the epidemiology of cutaneous melanoma is complex at best but strongly suggests that blistering sunburns during childhood and adolescence are particularly important in establishing a risk for subsequent carcinogenesis (5, 6), particularly in high-risk individuals; for example, in individuals with red hair color (RHC), melanocortin-1 receptor (MC1R) genotypes (7) or individuals with a large number of nevi, particularly those that are dysplastic (8). Epidemiology studies also support the notion that adults who experience intense intermittent sunlight exposure (e.g., indoor workers, sunlamps) are at increased risk for melanoma compared with those who receive their sun exposure chronically (6). In both the childhood and adult situations, there seems to be a long latent period before the end point of melanoma becomes manifest.