Serum Vitamin D and Mortality from Eye Melanoma

描述(申请人提供)：葡萄膜(眼)黑色素瘤是一种侵袭性肿瘤，发生在内眼的脉络膜组织中。这项研究的目的是检验血清维生素D水平是否是眼睛黑色素瘤的预后因素。维生素D是一种来自阳光照射的‘营养’。维生素D的激素活性形式1，25(OH)2D3(骨化三醇)是众所周知的强大的细胞生长和分化调节因子，表达维生素D受体(VDR)的细胞和组织中，最近有证据表明它对肿瘤的侵袭和转移具有抑制作用。然而，从人体研究中获得的数据有限。这项拟议的调查将基于波士顿马萨诸塞州眼耳医院13年来(1992-2004年)治疗的一大批眼睛黑色素瘤患者。马萨诸塞州眼耳医院是诊断和治疗这些肿瘤的领先转诊中心。在诊断时采集血液样本，并将血清和棕黄色涂层组分保存在-70℃。在这项计划中的研究中，将通过查看图表以及搜索社会保障和国家死亡指数来更新所有幸存患者的生命状态。在存储了血清和DNA的1,493名患者中，估计有272名死于肿瘤原因的患者(‘病例’)将被确定(中位数随访：8.7年)。对于每个病例，将选择一个匹配的对照，在临床预后因素和诊断年份方面与病例相似，且存活且无转移。将对血清样本进行钙二醇(25(OH)D3)水平测试，这是活性维生素D生物合成的仓库。维生素水平的病例对照比较将使用条件Logistic回归进行。还将检查VDR中的特定基因类型和单倍型与黑色素瘤预后的关系，并探讨与血清维生素D水平的相互作用。据我们所知，这将是这类研究的第一次，基于预期收集的血清和DNA的独特来源，以及对患者的长期随访。这项拟议的研究将提供有关维生素D与眼部黑色素瘤死亡率之间关系的新信息。由于维生素D被认为在癌症转移中具有多种抑制作用，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.