Plasma Vitamin D Levels and Prostate Cancer Outcomes

血浆维生素 D 水平和前列腺癌结果

基本信息

批准号：
8106146
负责人：
JANET L STANFORD
金额：
$ 8.54万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-06 至 2012-12-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8106146
关键词：
25-hydroxyvitamin D Admission activity African American Aging Apoptosis Baby Booms Biological Markers Blood specimen Body mass index Cancer Prognosis Cancer Survivor Case-Control Studies Cause of Death Cell Proliferation Cells Cessation of life Clinical Clinical Data Clinical Trials Clinical Trials Design Confidence Intervals Data Data Set Development Diagnosis Diagnostic Diagnostic Neoplasm Staging Disease Disease Outcome Disease Progression Epidemiologic Studies Epidemiology Evaluation Funding Genes Genetic Polymorphism Genetic Variation Genotype Gleason Grade for Prostate Cancer Grant Health Care Costs Histologic Hormones Hospitals Hypercalcemia In Vitro Incidence Incidence Study Kidney Lesion Malignant - descriptor Malignant Neoplasms Malignant neoplasm of prostate Measures Metabolism Modeling Morbidity - disease rate Neoplasm Metastasis Observational Study Outcome Pathway interactions Patients Plasma Play Process Prostate Prostate-Specific Antigen Prostatic Neoplasms Public Health Race Recurrence Regulation Reporting Research Research Design Risk Risk Estimate Role Sampling Serum Skin Societies Source Subgroup Sun Exposure Therapeutic Agents Time Tissues Treatment Efficacy Tumor stage VDR gene Vital Status Vitamin D Vitamin D Analog Vitamin D Deficiency Vitamins advanced disease adverse outcome androgen independent prostate cancer burden of illness calcification cancer recurrence cohort cost effective experience follow-up hazard high risk men improved in vivo innovation men migration mortality novel older men outcome forecast patient population population based public health relevance soft tissue success tumor tumor growth ultraviolet

项目摘要

DESCRIPTION (provided by applicant): A beneficial role for vitamin D in prostate cancer survivors is supported by anticancer effects consistently shown in both in vitro and in vivo studies, and by observational research reporting inverse associations between sunlight exposure and prostate cancer mortality. Vitamin D analogs have also shown therapeutic efficacy in selected patients. However, few epidemiological studies have specifically evaluated circulating vitamin D levels in relation to prostate cancer prognosis. This study will investigate whether plasma concentration of 25-hydroxyvitamin D [25(OH)D] in men diagnosed with prostate cancer is associated with disease outcomes. The study has the following specific aims: 1) To measure plasma concentration of 25(OH)D in a population-based cohort of prostate cancer cases; and, 2) To evaluate the association between plasma 25(OH)D concentrations with risks of prostate-cancer specific death and tumor recurrence or progression. To accomplish these aims we will build upon an existing population-based cohort of 1,477 histologically confirmed prostate cancer cases (with 6-18 years of follow-up) for which extensive epidemiological data, clinical data, post-diagnosis blood samples, and genetic variation in vitamin D metabolism genes (VDR, CYP27B1 and CYP24A1) have already been collected or measured. This unique cohort is under on-going follow-up for ascertainment of disease recurrence/progression, vital status and underlying cause of death (funded by a separate grant). Adjusted Cox proportional hazards regression models will be used to determine hazard ratios and 95% confidence intervals for the outcomes according to vitamin D level. We will also explore if these hazard ratios are modified by body mass index, race, or vitamin D metabolism genotypes. Associations also will be examined within patient subgroups defined by clinical parameters known to influence prostate cancer outcomes (Gleason score, tumor stage, diagnostic PSA level) and by primary treatment. Only one small epidemiological study has previously reported a positive association between serum concentration of 25(OH)D and prostate cancer survival. The proposed study will be the largest study to date to evaluate vitamin D level in prostate cancer survivors, and will include analyses of additional endpoints and evaluation of relevant subgroups. This innovative and cost-effective application to relate plasma vitamin D status with patient prognosis could provide evidence supporting the use of vitamin D level as a biomarker for identifying men at higher risk for adverse outcomes and bolster efforts to develop a vitamin D analog as a therapeutic agent for appropriate patients where vitamin D may have the greatest impact on prognosis. PUBLIC HEALTH RELEVANCE: Project Narrative In 2009 there will be an estimated 27,360 deaths from prostate cancer and a significant additional burden to the U.S. in terms of disease morbidity and health care costs for the 192,280 men diagnosed with prostate cancer. This study will measure vitamin D, a modifiable factor with demonstrated anti-cancer effects, in the plasma of men with prostate cancer and estimate the risks of cancer recurrence/progression and prostate cancer-specific death by vitamin D levels. Results from this study could be used to design clinical trials exploring the potentially beneficial effects of vitamin D in the treatment of certain patient populations with prostate cancer, thereby improving patient prognosis, and to develop vitamin D as a potential biomarker for patients with more aggressive disease.

描述（由申请人提供）：维生素 D 对前列腺癌幸存者的有益作用得到了体外和体内研究一致显示的抗癌作用以及报告阳光照射与前列腺癌死亡率之间负相关的观察性研究的支持。维生素 D 类似物也在选定的患者中显示出治疗效果。然而，很少有流行病学研究专门评估循环维生素 D 水平与前列腺癌预后的关系。本研究将调查诊断患有前列腺癌的男性中 25-羟基维生素 D [25(OH)D] 的血浆浓度是否与疾病结果相关。该研究有以下具体目标：1) 测量前列腺癌病例人群中 25(OH)D 的血浆浓度； 2) 评估血浆 25(OH)D 浓度与前列腺癌特异性死亡和肿瘤复发或进展风险之间的关联。为了实现这些目标，我们将建立一个现有的基于人群的队列，该队列由 1,477 例经组织学确诊的前列腺癌病例组成（随访 6-18 年），其中包含广泛的流行病学数据、临床数据、诊断后血液样本和遗传变异维生素 D 代谢基因（VDR、CYP27B1 和 CYP24A1）中的 CYP24A1 已经被收集或测量。这个独特的队列正在接受持续的随访，以确定疾病复发/进展、生命状态和根本死因（由单独的拨款资助）。调整后的 Cox 比例风险回归模型将用于根据维生素 D 水平确定结果的风险比和 95% 置信区间。我们还将探讨这些风险比是否会因体重指数、种族或维生素 D 代谢基因型而改变。还将在由已知影响前列腺癌结果的临床参数（格里森评分、肿瘤分期、诊断性 PSA 水平）和主要治疗定义的患者亚组中检查关联性。此前只有一项小型流行病学研究报道了 25(OH)D 血清浓度与前列腺癌存活率之间存在正相关。拟议的研究将是迄今为止评估前列腺癌幸存者维生素 D 水平的最大研究，并将包括其他终点的分析和相关亚组的评估。这种创新且经济有效的应用将血浆维生素 D 状态与患者预后联系起来，可以提供支持使用维生素 D 水平作为生物标志物的证据，用于识别不良结果风险较高的男性，并支持开发维生素 D 类似物作为治疗药物的努力适用于维生素 D 对预后影响最大的患者。公共健康相关性：项目叙述 2009 年，估计将有 27,360 人死于前列腺癌，并且在疾病发病率和 192,280 名被诊断患有前列腺癌的男性的医疗保健费用方面给美国带来了巨大的额外负担。这项研究将测量前列腺癌男性血浆中的维生素 D（一种已证实具有抗癌作用的可改变因子），并根据维生素 D 水平估计癌症复发/进展和前列腺癌特异性死亡的风险。这项研究的结果可用于设计临床试验，探索维生素 D 在治疗某些前列腺癌患者群体中的潜在有益作用，从而改善患者预后，并开发维生素 D 作为患有更具侵袭性疾病的患者的潜在生物标志物。