Colorectal Cancer

结直肠癌

基本信息

批准号：
7786694
负责人：
EDWARD GIOVANNUCCI
金额：
$ 46.3万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
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：
2010-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7786694
关键词：
25-hydroxyvitamin D Affect Archives Aspirin Biological Biological Assay Blood C-Peptide C-reactive protein Cancer Etiology Cancer Patient Cause of Death Cessation of life Characteristics Chemoprevention Colon Carcinoma Colorectal Colorectal Cancer Colorectal Neoplasms Complementary DNA DNA Data Analyses Databases Disease Etiology Excision Excretory function Exhibits Fatty-acid synthase GC gene Genes Genetic Genetic Predisposition to Disease Genetic Variation Genotype Hormonal Risk Factor Hydroxyprostaglandin Dehydrogenases Hyperinsulinism IGF1 gene IGFBP3 gene Incidence Individual Inflammation Inflammatory Insulin Interleukin-6 Investigation Joints KRAS2 gene Leadership Life Style Ligation Link Maintenance Malignant Neoplasms Measures Mediating Melatonin Mixed Function Oxygenases Molecular Weight Mutate Mutation Non-Steroidal Anti-Inflammatory Agents Nuclear Nurses&apos Health Study Nutritional Obesity PIK3CA gene PPARG gene Pathology Pathway interactions Patients Plasma Prevention strategy Preventive Questionnaires RXR Recurrence Research Infrastructure Risk Risk Reduction Role Sampling Supplementation Tumor Necrosis Factor-alpha Tumor Necrosis Factors Urine Variant Vitamin D Vitamin D3 Receptor Weight Woman Work adenoma adiponectin base cancer diagnosis cancer risk carcinogenesis cohort cyclooxygenase 2 disease diagnosis energy balance follow-up improved indexing inflammatory marker mRNA Expression mortality overexpression receptor response tumor urinary

项目摘要

In this Project, we propose to continue the investigation of potentially modifiable nutritional and hormonal risk factors for colorectal cancer, including those that affect survival after the diagnosis of this cancer. This work will use the stored blood and urine samples, archived DNA, repeated questionnaires, and long follow-up in the Nurses' Health Study (1976-2012 with approximately 2,220 incident colorectal cancers), and tumor characteristics using pathology blocks from approximately 1,554 colorectal cancers. We propose to examine 4 inter-related pathways for colorectal cancer: vitamin D, energy balance, inflammation, and melatonin. For aim 1, we propose to examine vitamin D status in relation to hypothesized tumor characteristics, and if preventive actions can be taken through vitamin D supplementation, particularly for women with elevated levels of plasma inflammatory factors. For aim 2, we will examine a comprehensive dietary measure of insulin response (dietary insulin index), clarify the joint and independent effects of adiponectin, and hyperinsulinemia, and identify genes involved in obesity-mediated colon cancer. For aim 3, we propose to better define aspirin chemoprevention of colorectal neoplasia based on COX-2 expression in the incident adenoma, to extend our work to inflammatory markers, and identify genes involved in aspirin-mediated chemoprevention. We will additionally examine the independent effect of these factors on survival following a resection of colorectal cancer. To accomplish this, we propose to link genetic alterations, modifiable factors, and hypothesized pathogenic mechanisms. This Project shares common biological and mechanistic themes with Projects 2, and 3, including the role of vitamin D, and energy balance in relation to cancer incidence and survival, and interacts closely with Project 4 for methodological issues. It also shares with the other Projects a strong scientific and administrative infrastructure provided by Cores A (cohort follow-up and data base maintenance), B (confirmation of cancer and cause of death), C (management of the biospecimens) and D (leadership and data analysis). The findings should enhance understanding of the etiology of colorectal cancer and aid in efforts to reduce incidence and death from this disease.

在这个项目中，我们建议继续研究结直肠癌的潜在可改变的营养和激素危险因素，包括那些在诊断出这种癌症后影响生存的因素。这项工作将使用护士健康研究中存储的血液和尿液样本、存档的 DNA、重复问卷和长期随访（1976 年至 2012 年，大约有 2,220 例结直肠癌病例），并使用来自大约 1,554 例结直肠癌的病理块来了解肿瘤特征癌症。我们建议检查结直肠癌的 4 种相互关联的途径：维生素 D、能量平衡、炎症和褪黑激素。为了目标 1，我们建议检查与假设的肿瘤特征相关的维生素 D 状态，以及是否可以通过补充维生素 D 采取预防措施，特别是对于血浆炎症因子水平升高的女性。对于目标 2，我们将检查胰岛素反应的综合饮食测量（膳食胰岛素指数），阐明脂联素和高胰岛素血症的联合和独立影响，并确定与肥胖介导的结肠癌有关的基因。对于目标 3，我们建议根据腺瘤中 COX-2 的表达，更好地定义阿司匹林对结直肠肿瘤的化学预防，将我们的工作扩展到炎症标志物，并鉴定参与阿司匹林介导的化学预防的基因。我们还将检查这些因素对结直肠癌切除术后生存的独立影响。为了实现这一目标，我们建议将遗传改变、可改变因素和假设的致病机制联系起来。该项目与项目 2 和 3 具有共同的生物学和机制主题，包括维生素 D 的作用以及与癌症发病率和癌症相关的能量平衡。生存，并在方法论问题上与项目 4 密切互动。它还与其他项目共享由核心 A（队列随访和数据库维护）、B（癌症和死因确认）、C（生物样本管理）和 D（领导力）提供的强大科学和行政基础设施和数据分析）。这些发现应该增强对结直肠癌病因的了解，并有助于减少这种疾病的发病率和死亡。