Plasma Vitamin D Levels and Prostate Cancer Outcomes

血浆维生素 D 水平和前列腺癌结果

• 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
• 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

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在前列腺癌幸存者中的有益作用得到了体外和体内研究中始终显示的抗癌作用，以及通过观察性研究报告阳光暴露与前列腺癌死亡率之间的反相关性。维生素D类似物还显示了选定患者的治疗功效。但是，很少有流行病学研究专门评估了与前列腺癌预后有关的循环维生素D水平。这项研究将研究被诊断出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局有关。该研究具有以下具体目的：1）在基于人群的前列腺癌病例中测量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的风险之间的关联。为了实现这些目标，我们将基于现有的基于人群的队列，该同类群体有1,477个组织学确认的前列腺癌病例（有6 - 18年的随访），为此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在维生素D代谢基因中（VDR，CYP27B1和COLC27B1和CYP224A1）已经cyp24aa Aa。这种独特的队列正在进行的随访中，以确定疾病复发/进展，生命状况和根本死亡原因（由单独的赠款资助）。根据维生素D水平，调整后的COX比例危害回归模型将用于确定结果的危害比和95％的置信区间。我们还将探索这些危险比是否通过体重指数，种族或维生素D代谢基因型来改变。还将在已知会影响前列腺癌结果（Gleason评分，肿瘤阶段，PSA诊断水平）和通过初级治疗的临床参数定义的患者亚组中检查关联。仅一项小型流行病学研究以前报道了25（OH）D的血清浓度与前列腺癌存活之间存在正相关。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，并将包括对其他终点的分析以及对相关亚组的评估。这种创新且具有成本效益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，以识别男性在不良后果的风险中识别出较高的不良风险，并加强对维生素D模拟剂作为适合维生素D的维生素D模拟剂的努力，其中维生素D可能对维生素D产生极大的影响。 公共卫生相关性：2009年的项目叙述将估计有27,360例前列腺癌死亡，并在192,280名被诊断出患有前列腺癌的男性的疾病发病率和医疗保健费用方面给美国带来了重大负担。这项研究将测量维生素D，这是一种可修改的因素，具有证明抗癌作用，在前列腺癌男性的血浆中，并估计维生素复发/进展/进展和维生素D水平的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，以探讨维生素D在治疗某些患有前列腺癌的患者种群中的潜在有益作用，从而改善患者的预后，并发展为患有更具侵略性疾病的患者的潜在生物标志物。