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Uveal melanoma is the most common primary intraocular malignancy, with an annual incidence of 6 per million. The environmental factors known to increase the risk of cutaneous melanoma appear to be less important in ocular melanoma and it is conceivable that host factors have a greater impact. The coexistence of ocular and cutaneous melanoma in some patients suggests a predisposition to both types and implicates mutations in the CDKN2A gene in a proportion of these cases. An association between ocular melanoma and breast and/or ovarian cancer has also been reported and recent studies of breast cancer families strongly implicate BRCA2 as a predisposition gene. Other more common genes predisposing to ocular melanoma may be of low penetrance. An example of a gene in this class is MC1R, which affects host response to ultraviolet radiation. Identification of genes conferring an increased risk of ocular melanoma should provide insights into the pathogenesis of this tumour. Furthermore, it offers an opportunity to identify individuals at a high risk who may benefit from targeted surveillance. At present the identification of such individuals is restricted to the small number belonging to BRCA2 families and those with the atypical mole syndrome.

Genetic predisposition to ocular melanoma