Plasma Vitamin D Levels and Prostate Cancer Outcomes

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的支持，并通过观察性研究报告了阳光照射与前列腺癌死亡率之间的负相关。维生素D类似物在某些患者中也显示出治疗效果。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。本研究将探讨前列腺癌患者血浆25-羟基维生素D [25(OH)D]浓度是否与疾病预后相关。本研究有以下具体目的：1)在以人群为基础的前列腺癌患者队列中测量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风险之间的关系。为了实现这些目标，我们将建立一个现有的以人群为基础的队列，其中有1477例组织学证实的前列腺癌病例（随访6-18年），已经收集或测量了广泛的流行病学数据、临床数据、诊断后血液样本和维生素D代谢基因（VDR、CYP27B1和CYP24A1）的遗传变异。正在对这一独特队列进行持续随访，以确定疾病复发/进展、生命状况和潜在死亡原因（由单独赠款资助）。采用调整后的Cox比例风险回归模型，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受到体重指数、种族或维生素D代谢基因型的影响。根据已知影响前列腺癌预后的临床参数（Gleason评分、肿瘤分期、诊断性PSA水平）和初级治疗确定的患者亚组内的关联也将进行检查。以前只有一项小型流行病学研究报告了血清25(OH)D浓度与前列腺癌生存率之间的正相关。拟议中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和相关亚组的评估。这一将血浆维生素D水平与患者预后联系起来的创新且具有成本效益的应用，可以为使用维生素D水平作为识别不良结局高风险男性的生物标志物提供证据，并支持开发维生素D类似物作为治疗药物，用于维生素D可能对预后影响最大的适当患者。

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.