Uveal Melanoma: Beyond a Baptism

Ophthalmologists focus on a very specialized region of the body; however, our years of general medical training are useful for patients, especially those with uveal melanoma. While hereditary uveal melanoma (UM) is very rare (<1% of uveal melanomas) [1], patients with a high frequency of personal and/or family history of cancer are found inabout 12% of unselected patients with UM [2]. The increased cancer predisposition is not limited to UM and isa diverse cancer phenotype. It is interesting that concurrent second primary cancers have been reported in 8-13% of patients with UM [3-6]. Furthermore, some studies have detected a small increased risk of additional primary malignancies in UM patients [3,7]. In the Collaborative Ocular Melanoma Study, the 10 year cumulative rate of second primary cancer was 14.9% (95% CI 12.9-17.1%), while the estimated 10-year rate for similar patients was only 9% [6]. Interestingly, the COMS excluded patients who had prior malignancy; thus,the increased rate of second primary cancer is striking since the exclusion criteria likely created a bias against patients with elevated cancer predisposition. These studies suggest that a subset of patients with UM is at an increased risk of cancer. Why do some UM patients have the propensity to develop multiple cancers? Is this the effect of inheritance of one dominant gene or a combination of multiple genes? Is there any genetic/environmental interaction? The answers to these questions are unknown at this time.