Clinical Trial of Vitamin D3 to Reduce Cancer Risk in Postmenopausal Women

维生素 D3 降低绝经后妇女癌症风险的临床试验

• 批准号: 7810241
• 负责人: JOAN LAPPE
• 金额: $ 62.32万
• 依托单位: CREIGHTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2011-09-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7810241
• 关键词: 25-hydroxyvitamin D; Accounting; Address; American; Area; Bioinformatics; Blood; Calcium; Candidate Disease Gene; Cholecalciferol; Clinical Trials; Cytochrome P450; Data; Data Analyses; Disease; Dose; Elderly; Environmental Risk Factor; Epidemiology; Female; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Haplotypes; Health; Individual; Intake; Intervention; Intervention Trial; Knowledge; Malignant Neoplasms; Measurement; Metabolism; Mission; Mixed Function Oxygenases; Molecular; Molecular Biology; Not Hispanic or Latino; Outcome; Parents; Participant; Patients; Persons; Phenotype; Physicians; Population; Postmenopause; RXR; Reporting; Research; Research Design; Research Proposals; SNP genotyping; Sampling; Schedule; Serum; Signal Pathway; Supplementation; Testing; Time; Variant; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamin D3 Receptor; Woman; Work; base; cancer prevention; cancer risk; cohort; gene interaction; genetic epidemiology; genetic variant; group intervention; high risk; improved; innovation; multidisciplinary; population based; prevent; receptor; research study; response

DESCRIPTION (provided by applicant): Serum 25(OH)D is prevalently low in older people and more than 60% North American female populations are below the optimal level. Low serum 25(OH)D is a serious problem since optimal serum 25(OH)D concentration is essential for preventing cancer and other disorders. Currently, vitamin D supplementation is the best approach in achieving adequate serum 25(OH)D levels. However, the change in serum 25(OH)D in response to a given dose of vitamin D supplementation varies widely from person to person and the factors underlying the variability are unknown. The unknown factors are likely genetic because both baseline serum 25(OH)D and the response to vitamin D intake are highly genetically determined. Currently, few genetic studies are available in this area. The specific genes underlying the response variability in serum 25(OH)D in different individual are unknown. By taking advantage of the large-size, homogeneous, unique, longitudinal, population-based, and high-dose vitamin D intervention trial sample from the parent study (R01CA129488), the primary objective of the revision is to identify genetic variants responsible for the variability in serum 25(OH)D levels. The central hypothesis is that genes functionally important for vitamin D metabolism and signaling pathways are involved in the variation of serum 25(OH)D levels in postmenopausal women. To test this hypothesis, eight prominent candidate genes have been selected. The specific aims are to: 1) identify the genetic variants responsible for the baseline serum 25(OH)D variation; 2) identify the genetic variants responsible for the response variability in serum 25(OH)D levels. For specific aim 1, the sample will be the entire cohort (n=2300) of non-Hispanic, white postmenopausal women. The targeted phenotype is baseline serum 25(OH)D variation. For specific aim 2, only subjects in the calcium (1200 mg/d) and vitamin D (2000 IU/d) intervention group (n=1150) will be used. The phenotype (endpoint) is the change of 12-month serum 25(OH)D in response to vitamin D supplementation. This revision proposal is highly innovative. It will yield additional critical information and will add value to the parent study. It is the first attempt to identify genetic factors responsible for variability in serum 25(OH)D in response to vitamin D supplementation. In addition, for the first time, it will address whether genes responsible for baseline serum 25(OH)D variation also account for the response variability in serum 25(OH)D. The genetic factors identified from this revision are important for understanding the mechanisms accounting for population variation in prevalent vitamin D status, and for individualizing dosing with vitamin D supplementation.

描述（由申请人提供）：老年人的血清25（OH）D普遍低，而北美女性的60％以上的人口低于最佳水平。低血清25（OH）D是一个严重的问题，因为最佳血清25（OH）D浓度对于预防癌症和其他疾病至关重要。目前，补充维生素D是达到足够的血清25（OH）D水平的最佳方法。然而，响应于给定剂量的维生素D补充剂的血清25（OH）D的变化因人而异，而变异性的因素却未知。未知因素可能是遗传因素，因为基线血清25（OH）D和对维生素D摄入的反应在高度遗传上确定。目前，该领域很少有遗传研究。在不同个体中血清25（OH）D中反应变异性的基因是未知的。通过利用父母研究中的大型，同质，独特的，纵向的，基于人群和高剂量维生素D干预试验样本（R01CA129488），修订的主要目的是确定遗传变异型负责血清25（OH）D水平的变异性。中心假设是，基因对维生素D代谢和信号传导途径在功能上很重要，与绝经后女性血清25（OH）D水平的变化有关。为了检验该假设，已经选择了八个著名的候选基因。具体目的是：1）确定负责基线血清25（OH）D变化的遗传变异； 2）确定负责血清25（OH）D水平反应变异性的遗传变异。对于特定的目标1，样本将是非西班牙裔，绝经后妇女的整个队列（n = 2300）。靶向表型是基线血清25（OH）D变化。对于特定目标2，仅使用钙（1200 mg/d）和维生素D（2000 IU/d）干预组（n = 1150）中的受试者。表型（终点）是响应维生素D补充的12个月血清25（OH）D的变化。该修订建议具有很高的创新性。它将产生其他关键信息，并为父母的研究增加价值。这是鉴定导致血清25（OH）d变异性的遗传因素的首次尝​​试，以响应维生素D补充。此外，它首次将解决负责基线血清25（OH）d变化的基因是否也解释了血清25（OH）d的响应变异性。从本修订中鉴定出的遗传因素对于理解构成普遍维生素D状态种群变化的机制以及补充维生素D的个性化给药很重要。