Etiology of melanoma.

Epidemiological and etiological research on the pathogenesis of melanoma remins a controversial issue. The main reason for this appears to rest on the relation between the genetically determined susceptibility of the host and ultraviolet radiation (UVR). Basic to understanding this, however, is the knowledge of the clinical and histopathological, the genotypical and phenotypical heterogeneity of this tumor entity. In terms of the multistage concept of carcinogenesis, melanocytes, atypical or normal, are exposed to a mutagenic event, predominantly UVR, initiating malignant growth in a genetically altered and susceptible genome. The initiation could also occur spontaneously or as the result of other insults such as chemical carcinogens, viral infections, ionizing radiation, etc. Promotion through the stage of melanocytic dysplasia or de novo from unaltered skin follows additional exposure to UVR or cocarcinogens and is likely to be modulated by ethnic, dietary, endocrine, but also protective factors and concomitant disease. In terms of descriptive epidemiology, melanoma may be caused by exposure to intermittent and intense sunlight on unacclimatized skin. The mechanism of this association, such as the wavelength responsible, effects of total dose, intensity of dose rate, latency period between exposure and the clinical incidence of disease, and finally, the stage of carcinogenesis affected by UVR and other initiating factors, as well as the impact of any specific modulation for the pathogenesis and clinical course of the disease remain to be elucidated.