Serum Vitamin D and Mortality from Eye Melanoma

描述（由申请人提供）：葡萄膜（“眼睛”）黑色素瘤是在内眼脉络膜组织中进化的侵袭性肿瘤。这项研究的目的是检验血清中维生素D（一种来自阳光照射的“营养素”）的水平是否是眼部黑色素瘤的预后因素。维生素D的激素活性形式，1,25(OH)2D3（骨化三醇），在表达维生素D受体（VDR）的细胞和组织中是一种众所周知的有效的细胞生长和分化调节剂，最近有证据表明它对肿瘤的侵袭和转移有抑制作用。然而，只有有限的数据可从人体研究。这项拟议的研究将基于在波士顿的马萨诸塞眼耳医院（Massachusetts eye and Ear Infirmary）治疗了13年（1992-2004）的大量眼部黑色素瘤患者，该医院是诊断和治疗这些肿瘤的主要转诊中心。诊断时采集血样，血清和灰褐色皮毛部分保存在-70℃。在计划的研究中，将通过图表审查和对社会保障和国家死亡指数的搜索来更新所有幸存患者的重要状态。在保存了血清和DNA的1493名患者中，估计将确定272例肿瘤死亡（“病例”）（中位随访时间：8.7年）。对于每个病例，将选择一个匹配的对照，临床预后因素和诊断年份与病例相似，存活且无转移。将检测血清样本的钙二醇（25(OH)D3）水平，钙二醇是活性维生素d的生物合成库。维生素水平的病例对照比较将使用条件逻辑回归进行。VDR中的特定基因型和单倍型也将被检查与黑色素瘤结果的关系，并将探索与血清维生素D水平的相互作用。据我们所知，这将是此类调查的第一次，基于前瞻性收集的独特血清和DNA资源，以及长期的患者随访。这项拟议的研究将为维生素D与眼部黑色素瘤死亡率之间的关系提供新的信息。由于维生素D被认为在癌症转移中具有多重抑制作用，因此该数据可能适用于其他癌症部位。如果提出的假设得到支持，研究结果可能会提供新的见解，并指出癌症控制的新策略。

DESCRIPTION (provided by applicant): 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.