No N-ras mutations in human uveal melanoma: the role of ultraviolet light revisited

Abstract

cases (Van't Veer et al., 1989). The primary tumours of these 7 patients were exclusively located on continuously sunexposed body sites. These mutations were all near dipyrimidine sites, suggesting an active role for ultraviolet (UV) radiation in the induction of the mutations. Shukla et al. (1989) found in one out of 22 tested primary cutaneous melanomas N-ras mutation in codon 61, but no details of sun exposure were available. Melanoma of the uvea (iris, ciliary body and choroid) is the most common primary intraocular malignancy in adults (Cutler & Young, 1975). The incidence of uveal melanoma in whites is eight times the incidence in blacks and threefold greater than in certain Asian groups (Hakulinen et al., 1987). In the Caucasian population individuals with light irides have three times the risk of developing uveal melanoma compared to persons with brown eyes (Gallagher et al., 1985). Early life exposures to sunlight have been found to be especially important in the development of intra-ocular melanoma. (Tucker et al., 1985). Recent epidemiological studies have reported an elevated risk for Northern European ancestry, light skin colour, the presence of 10 or more cutaneous naevi, use of sunlamps a-nd intense sun exposure (Seddon et al., 1990). Holly et al. (1990) found an increased risk of developing uveal melanoma for the apparent effects of UV exposure (severe eye burn, snow blindness), and for host factors, like light eye colour and a propensity to burn rather than tan. These findings implicate sunlight as an environmental risk factor for this disease. The colour of the iris is determined by the degree of pigmentation; limited pigmentation leads to a blue or grey iris and high concentrations of melanin are present in brown irides. Melanin can absorb UV as well as visible light. To investigate possible UV mediated activation of N-ras