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发展的侵袭性肿瘤。这项研究的目的是检查血清中维生素D的水平，一种来自阳光照射的“营养素”，是否是眼睛黑色素瘤的预后因素。维生素D的药物活性形式1，25（OH）2D 3（骨化三醇）是众所周知的表达维生素D受体（VDR）的细胞和组织中细胞生长和分化的有效调节剂，并且最近有证据表明其对肿瘤侵袭和转移具有抑制作用。然而，只有有限的数据可从人类研究。该研究将基于在波士顿马萨诸塞州眼耳医院（一家诊断和治疗这些肿瘤的主要转诊中心）治疗了13年（1992-2004）的大量眼黑色素瘤患者。在诊断时收集血液样品，并将血清和血沉棕黄层部分储存在-70 ℃下。在计划的研究中，将通过病历审查和检索社会保障和国家死亡指数，更新所有存活患者的生命状态。在1，493名储存了血清和DNA的患者中，估计将确定272例因肿瘤原因死亡（“病例”）（中位随访时间：8.7年）。对于每例病例，将选择一个匹配的对照，其在临床预后因素和诊断年份方面与病例相似，并且存活且无转移。将检测血清样本的骨化二醇（25（OH）D3）水平，骨化二醇是活性维生素D生物合成的储存库。将使用条件logistic回归进行维生素水平的病例对照比较。还将检查VDR中的特定基因型和单倍型与黑色素瘤结局的关系，并探索与血清维生素D水平的相互作用。据我们所知，这将是第一次基于前瞻性收集的血清和DNA的独特资源以及长期患者随访的此类调查。这项拟议的研究将提供有关维生素D与眼黑色素瘤死亡率关系的新信息。由于维生素D被认为在癌症转移中具有多种抑制作用，因此该数据可能适用于其他癌症部位。如果所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.