Serum Vitamin D, Genetic Polymorphisms & Ovarian Cancer

血清维生素 D、遗传多态性

• 批准号: 6796066
• 负责人: Alan A. Arslan
• 金额: $ 8.22万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-12 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6796066
• 关键词: 25 hydroxycholecalciferol; Scandinavian country; United States; biomarker; cancer risk; cell differentiation; cell growth regulation; clinical research; female; genetic polymorphism; genetic susceptibility; human genetic material tag; human subject; ovary neoplasms; patient oriented research; serum; vitamin D; vitamin D deficiency; vitamin D receptors; women' s health

DESCRIPTION (provided by applicant): Recent experimental data revealed that in addition to its well-known role in mineral and skeletal metabolism, vitamin D is involved in the regulation of growth, differentiation and function of a wide range of normal and malignant cells. Vitamin D-specific receptors are present in normal mammalian ovaries, in human ovarian tissues and in the ovarian carcinoma cell lines. Administration of active vitamin D compounds had been associated with a considerable prodifferentiation and antiproliferative changes in ovarian cells, induction of apoptosis, modulation of growth factor signaling and inhibition of invasion and metastasis. The current application proposes to test the hypothesis that vitamin D may be essential in supporting the differentiated/antiproliferative phenotype of ovarian cells, whereas hypovitaminosis D (due to low serum levels of active vitamin D compounds and/or due to vitamin D receptor gene polymorphisms) is associated with an increased risk of ovarian cancer. The primary specific aim of this application is to conduct the first analytical study to examine serum levels of 25-hydroxyvitamin-D3, an active form of vitamin D, as biomarker of ovarian cancer risk. The secondary specific aim is to assess the possible role of functional vitamin D receptor gene polymorphisms (Taql, BsmI, ApaI, poly-A microsatellite) in ovarian cancer. The proposed nested case-control study is based on two existing prospective cohorts: the New York University Women's Health Study (NYUWHS) and the Northern Sweden Health and Disease Study (NSHDS). Besides the valuable source of biological specimens, which include serum and DNA samples, NYUWHS and NSHDS provide the established mechanisms of follow-up. At least 136 cases of ovarian cancer are available for the study (80 cases from the NYUWHS and 56 cases from the NSHDS), as well as 272 individually-matched controls. Demonstration of the role of vitamin D as a potential biomarker of ovarian cancer risk would have a direct clinical implications: 1) serum levels of vitamin D and/or vitamin D receptor polymorphisms could be used to identify women at increased risk of ovarian cancer, which is currently characterized by lack of reliable biomarkers for screening and early detection; 2) an intervention with vitamin D analogues with limited calcium mobilizing activity could be a potentially new therapeutic approach for primary chemoprevention of ovarian cancer.

描述（由申请人提供）： 最近的实验数据显示，除了其在矿物质和骨骼代谢中的众所周知的作用外，维生素D还参与调节各种正常和恶性细胞的生长、分化和功能。维生素D特异性受体存在于正常哺乳动物卵巢、人卵巢组织和卵巢癌细胞系中。活性维生素D化合物的给药与卵巢细胞中相当大的促分化和抗增殖变化、诱导凋亡、调节生长因子信号传导以及抑制侵袭和转移相关。 本申请提出测试维生素D可能在支持卵巢细胞的分化/抗增殖表型中是必需的，而维生素D缺乏症（由于活性维生素D化合物的低血清水平和/或由于维生素D受体基因多态性）与卵巢癌风险增加相关的假设。 本申请的主要具体目的是进行第一项分析研究，以检查血清中25-羟基维生素D3（维生素D的活性形式）的水平，作为卵巢癌风险的生物标志物。第二个具体目标是评估功能性维生素D受体基因多态性（Taql，BsmI，ApaI，poly-A微卫星）在卵巢癌中的可能作用。 拟议的巢式病例对照研究是基于两个现有的前瞻性队列：纽约大学妇女健康研究（NYUWHS）和北方瑞典健康与疾病研究（NSHDS）。除了包括血清和DNA样本在内的生物标本的宝贵来源外，纽约大学妇女卫生系统和国家卫生和健康发展系统还提供了既定的后续机制。至少有136例卵巢癌病例可用于研究（80例来自NYUWHS，56例来自NSHDS），以及272例个体匹配的对照。 证明维生素D作为卵巢癌风险的潜在生物标志物的作用将具有直接的临床意义：1）血清维生素D和/或维生素D受体多态性水平可用于识别卵巢癌风险增加的妇女，目前其特征在于缺乏用于筛查和早期检测的可靠生物标志物; 2）钙动员活性有限的维生素D类似物的干预可能是卵巢癌初级化学预防的潜在新治疗方法。