A Pooled Analysis of 25-hydroxyvitamin D and Colorectal Cancer Survival

25-羟基维生素 D 与结直肠癌生存的汇总分析

• 批准号: 8773987
• 负责人: Veronika Fedirko
• 金额: $ 9.34万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8773987
• 关键词: 25-hydroxyvitamin D; Adopted; Affect; Androgen Receptor; Animals; Asia; Basic Science; Biological; Biological Markers; Blood; Body mass index; Cancer Etiology; Cancer Patient; Cancer Survivor; Cell Cycle; Cessation of life; Characteristics; Chemoprevention; Chemopreventive Agent; Cohort Effect; Cohort Studies; Collection; Colon; Colon Carcinoma; Colonic Neoplasms; Colorectal Cancer; Coupled; Data; Data Protection; Development; Diagnosis; Diagnostic; Diet; Dietary Calcium; Dietary Factors; Disease; Early Diagnosis; Early treatment; Epidemiologic Studies; Estrogen Receptors; Europe; Funding; Future; Genetic Polymorphism; Genetic Variation; Goals; Growth Factor; Habits; Human; Incidence; Inflammation; Investigation; Laboratories; Lead; Life; Life Style; Measures; Meta-Analysis; Neoplasm Metastasis; Outcome; Oxidative Stress; Parents; Pathway interactions; Patients; Persons; Physical activity; Population; Prevention; Prospective Studies; Publishing; Quality of life; Randomized Clinical Trials; Randomized Controlled Trials; Receptor Gene; Rectal Cancer; Recurrence; Reporting; Resources; Risk; Risk Factors; Seasons; Signal Transduction; Site; Smoking; Staging; Subgroup; Supplementation; Survival Analysis; Treatment Effectiveness; Treatment Protocols; Tumor Subtype; Vitamin D; Vitamin D3 Receptor; Vitamins; adverse outcome; angiogenesis; anticancer treatment; base; calcium intake; cancer diagnosis; cancer recurrence; cancer risk; cancer site; cancer therapy; cohort; colorectal cancer screening; cost effective; immune function; improved; insight; lifestyle factors; malignant breast neoplasm; modifiable risk; mortality; parent grant; prevent; prospective; public health relevance; screening; sex; tertiary prevention; time interval; tumor; tumor progression

DESCRIPTION (provided by applicant): Despite advances in prevention, screening, early detection, and treatment, colorectal cancer (CRC) remains the 3rd most commonly diagnosed cancer and the 2nd leading cause of cancer death in the US, with approximately 142,820 new cases and 50,830 deaths expected in 2013. Although advances in CRC early detection and treatment have resulted in relatively longer survival, the impact of modifiable dietary and lifestye factors that may contribute to survival has not been sufficiently explored. Vitamin D is a potentia agent for the chemoprevention of cancer progression, recurrence and death in CRC patients, possibly through mechanisms related to its direct effects on the cell cycle, modulation of growth factor signaling, estrogen and androgen receptor pathways, inflammation, oxidative stress, and immune function, as well as inhibition of invasion, metastasis, and angiogenesis. Higher circulating vitamin D levels are consistently associated with lower risk for CRC, but their association with CRC survival is relatively unexplored. Based on basic science and limited human evidence, we hypothesize that higher levels of prospectively collected, pre-diagnostic circulating vitamin D [25(OH)D, the best indicator of vitamin D status] are associated with lower CRC-specific and overall mortality among CRC cases. We will investigate this in an adjunct study to the ongoing, NCI-funded (R01 CA152071) Vitamin D Pooling Project of Breast and Colorectal Cancer (VDPP), which pools comprehensive primary data from 21 prospective cohort studies from the US, Europe, and Asia to investigate associations between 25(OH)D levels and risk of these cancer sites overall, by tumor subtype, and by population subgroups defined by personal characteristics, lifestyle factors, vitamin D receptor (VDR) polymorphisms, and other biomarkers. We will analyze (using traditional and competing risk survival analyses) the association between pre-diagnostic 25(OH) D levels and risk of CRC-specific and overall mortality in 5,795 CRC cases (among which there were 2,627 deaths) in 16 cohort studies conducted in the US, Europe, and Asia. As part of the parent grant, the 25(OH) D levels have been calibrated to a common standard laboratory to enable categorization of 25(OH)D levels using not only study-specific quintiles, but also consortium-wide quintiles and common absolute cut points. This adjunct study offers a unique, cost-effective and resource-efficient opportunity i the largest pooled study currently available to investigate an association between pre-diagnostic 25(OH)D levels and CRC-specific and overall mortality, with particular emphasis on potential lifestyle (body mass index, physical activity, calcium intake) and genetic (variation in the VDR in a sub-set of cohorts) effect modifiers, and examine the effects of vitamin D on CRC survival by colon sub-site, sex, and tumor characteristics. This study will provide an important step forward in understanding whether vitamin D affects CRC progression and survival, as well as insight into the potential application of this important compound in CRC treatment regimens.

描述（由申请人提供）：尽管在预防、筛查、早期检测和治疗方面取得了进展，但结直肠癌（CRC）仍然是美国第三大最常诊断的癌症和第二大癌症死亡原因，预计2013年约有142，820例新发病例和50，830例死亡。尽管CRC早期发现和治疗的进展导致了相对较长的生存期，但可能有助于生存的可改变的饮食和生活方式因素的影响尚未得到充分探讨。维生素D是化学预防CRC患者癌症进展、复发和死亡的有效药物，可能通过其对细胞周期、生长因子信号传导、雌激素和雄激素受体途径、炎症、氧化应激和免疫功能的调节以及对侵袭、转移和血管生成的抑制的直接作用机制。较高的循环维生素D水平始终与CRC风险较低相关，但其与CRC生存率的相关性相对未被探索。基于基础科学和有限的人类证据，我们假设前瞻性收集的较高水平的诊断前循环维生素D [25（OH）D，维生素D状态的最佳指标]与CRC病例中较低的CRC特异性和总体死亡率相关。我们将在一项正在进行的、由国家癌症研究所资助的（R01 CA152071）乳腺癌和结直肠癌维生素D汇总项目（VDPP），该项目汇总了来自美国、欧洲和亚洲的21项前瞻性队列研究的综合原始数据，以按肿瘤亚型调查25（OH）D水平与这些癌症部位总体风险之间的相关性，以及由个人特征、生活方式因素、维生素D受体（VDR）多态性和其他生物标志物定义的人群亚组。我们将在美国、欧洲和亚洲进行的16项队列研究中分析（使用传统和竞争性风险生存分析）5，795例CRC病例（其中2，627例死亡）的诊断前25（OH）D水平与CRC特异性和总体死亡率风险之间的关系。作为母基金的一部分，25（OH）D水平已被校准到一个共同的标准实验室，以便不仅使用研究特定的五分位数，而且使用全联盟的五分位数和共同的绝对分界点对25（OH）D水平进行分类。这项辅助研究提供了一个独特的，具有成本效益和资源效率的机会，目前最大的汇总研究，以调查诊断前25（OH）D水平与CRC特异性和总体死亡率之间的关系，特别强调潜在的生活方式（体重指数，体力活动，钙摄入量）和遗传（VDR的变化， 一个小组）效应调节剂，并通过结肠亚部位、性别和肿瘤特征检查维生素D对CRC存活的影响。这项研究将为了解维生素D是否影响CRC进展和生存提供重要的一步，以及深入了解这种重要化合物在CRC治疗方案中的潜在应用。