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，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 年将有约 142,820 例新病例和 50,830 例死亡。尽管结直肠癌早期检测和治疗方面的进步导致相对较长的生存期，但可改变的饮食和生活方式因素的影响可能会影响结直肠癌。 生存的问题尚未得到充分探讨。维生素 D 是一种化学预防 CRC 患者癌症进展、复发和死亡的强效剂，其机制可能与其直接影响细胞周期、调节生长因子信号、雌激素和雄激素受体途径、炎症、氧化应激和免疫功能以及抑制侵袭、转移和血管生成有关。较高的循环维生素 D 水平始终与较低的 CRC 风险相关，但其与 CRC 存活率的关系相对尚未被探索。基于基础科学和有限的人类证据，我们假设前瞻性收集的诊断前循环维生素 D [25(OH)D，维生素 D 状态的最佳指标] 水平较高与 CRC 病例中较低的 CRC 特异性死亡率和总体死亡率相关。我们将在一项由 NCI 资助的 (R01 CA152071) 乳腺癌和结直肠癌维生素 D 汇集项目 (VDPP) 的辅助研究中对此进行调查，该项目汇集了来自美国、欧洲和亚洲的 21 项前瞻性队列研究的综合主要数据，以调查 25(OH)D 水平与这些癌症部位整体风险之间的关联，按肿瘤亚型以及由个人特征定义的人群亚组， 生活方式因素、维生素 D 受体 (VDR) 多态性和其他生物标志物。我们将在美国、欧洲和亚洲进行的 16 项队列研究中，对 5,795 例 CRC 病例（其中 2,627 例死亡）分析（使用传统和竞争风险生存分析）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联。作为家长资助的一部分，25(OH)D 水平已根据通用标准实验室进行校准，以便不仅使用特定于研究的五分位数，还使用联盟范围的五分位数和通用绝对切点对 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，是目前可用于调查诊断前 25(OH)D 水平与 CRC 特异性和总体死亡率之间关系的最大的汇总研究，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） 队列的子集）效应调节剂，并通过结肠亚位点、性别和肿瘤特征检查维生素 D 对 CRC 存活的影响。这项研究将在了解维生素 D 是否影响 CRC 进展和生存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方面迈出重要一步。