Uveal ('eye') melanomas are aggressive neoplasms that evolve in the choroidal tissues of the inner eye. The goal of this research is to examine whether serum levels of vitamin D, a 'nutrient' derived from sun exposure, is a prognostic factor in melanoma of the eye. The hormonally active form of vitamin D, 1,25(OH)2D3 (calcitriol), is a well-known potent regulator of cell growth and differentiation in cells and tissues expressing the vitamin D receptor (VDR), and there is recent evidence of an inhibiting effect on tumor invasion and metastasis. However, only limited data are available from human studies. The proposed investigation will be based on a large series of eye melanoma patients treated over a 13 year period (1992-2004) at the Massachusetts Eye and Ear Infirmary, in Boston, a leading referral center for diagnosis and treatment of these tumors. Blood samples were collected at the time of diagnosis and serum and buffy coat fractions were stored at -70C. In the planned study, vital status of the patients will be updated on all surviving patients by chart review and a search of the Social Security, and National Death Indexes. Of 1,493 patients with stored sera and DNA, an estimated 272 deaths from tumor causes (the 'cases') will be identified (median follow up: 8.7 years). For each case, one matched control will be selected, similar to the case on clinical prognostic factors and year of diagnosis, and alive and free of metastasis. Serum samples will be tested for levels of calcidiol (25(OH)D3), the depot for biosynthesis of active vitamin D. Case-control comparisons for vitamin levels will be performed using conditional logistic regression. Specific genotypes and haplotypes in the VDR will also be examined for relationships to melanoma outcome, and interactions with serum vitamin D levels will be explored. To our knowledge, this will be the first investigation of its kind, based on a unique resource of prospectively collected serum and DNA, and long-term patient follow up. The proposed study will provide new information on the relationship of vitamin D to mortality from eye melanoma. Because vitamin D is believed to have multiple inhibitory actions in cancer metastasis, the data may be applicable to other cancer sites. If the proposed hypotheses are supported, findings may offer novel insights, and point to new strategies for cancer control. ? ? ?
