Insulin Resistance Syndrome Pathway Factors and Colon Polyps

胰岛素抵抗综合征途径因素和结肠息肉

基本信息

批准号：
7901121
负责人：
Li Li
金额：
$ 36.62万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7901121
关键词：
Address Affect Biological Biological Markers Biological Models Blood specimen Candidate Disease Gene Case-Control Studies Colon Colon Carcinoma Colonic Adenoma Colonic Neoplasms Colonic Polyps Colonoscopy Data Development Diet Dietary Factors Dietary Practices Epidemic Epidemiologic Studies Equation Etiology Food Frequencies Genes Genetic Genetic Polymorphism Genetic Variation Genotype Glycemic Index Goals Haplotypes Hormones Human Incidence Individual Insulin Insulin Resistance Insulin-Like Growth Factor I Insulin-Like Growth-Factor Binding Protein 1 Intervention Joints Life Style Link Malignant Neoplasms Mediating Metabolic Metabolism Modeling Non-Insulin-Dependent Diabetes Mellitus Nutrient Obesity PPAR gamma Pathway interactions Peroxisome Proliferator-Activated Receptors Play Predisposition Preventive Intervention Process Public Health Questionnaires Recruitment Activity Research Risk Risk Factors Role Screening procedure Serum Markers Societies Somatomedins Somatotropin Staging Statistical Methods Statistical Models Syndrome Time Work adiponectin base colon carcinogenesis disorder risk insulin receptor substrate 1 protein lipid biosynthesis novel

项目摘要

Increasing evidence from both model systems and epidemiologic studies support that insulin resistance resulting from long-term energy imbalance plays an important role in colon carcinogenesis. The fact that the incidences of obesity, insulin resistance syndrome, and type 2 diabetes are escalating at epidemic pace worldwide makes the exploration of the insulin resistance-colon neoplasia hypothesis a subject of pressing priority. We hypothesize that candidate genes and associated biomarkers in the insulin-growth hormone-insulin-like growth factor (IGF)-insulin receptor substrate 1 (IRS-1) axis, adipogenesis pathway (adiponectin, and peroxisome proliferator-activated receptor-gamma), and dietary factors may work jointly to drive the development of insulin resistance syndrome, and subsequently, the development of colon adenomatous polyps, established precursors of colon cancer. We propose a screening colonoscopy-based incident case-control study to address the insulin resistance syndrome-colon polyp hypothesis by prospectively recruiting 750 incident colon polyp cases and 750 frequency-matched controls. We will determine the candidate gene variants and haplotypes, associated biomarkers, and insulin resistance syndrome related serum markers using blood samples, and collect dietary and lifestyle risk factor information using questionnaires. We will analyze the resulting information using novel statistical models to gain comprehensive understanding of the link between insulin resistance syndrome and colon polyps. Specifically, we will 1) to investigate the impact of insulin resistance syndrome as an integral entity on colon polyps; 2) to examine the impact of candidate genes and associated biomarkers in the insulin-GH-IGF-IRS axis and adipogenesis pathway on colon polyps; 3) to evaluate the association of dietary patterns, glycemic index and glycemic load with colon polyps; and 4) to synthesize the information on candidate genes, biomarkers, and diet by looking at their joint effects on colon polyps, and to comprehensively evaluate these factors' potential direct as well as indirect (mediated by insulin resistance syndrome) impact on colon polyps. Our study will contribute to our understanding of how insulin resistance syndrome pathway-related candidate genes and dietary factors might work in concert in the etiology of colon adenomatous polyps. Our study may have profound implication for public health prevention/intervention strategies targeting at the early stages of the colon adenoma-cancer continuum.

越来越多的证据来自模型系统和流行病学研究支持，即长期能量失衡引起的胰岛素抵抗在结肠癌发生中起重要作用。肥胖，胰岛素抵抗综合征和2型糖尿病的发生率在全球流行速度上升级，这使得探索了胰岛素抵抗 - 抗性神经肿瘤假设，这是压迫优先级的主题。我们假设候选基因和相关的生物标志物在胰岛素增长激素 - 胰岛素样生长因子（IGF） - 胰岛素受体底物1（IRS-1）轴，脂肪生成途径（脂联蛋白和过氧化物酶体增殖量增殖的受体含量和饮食因子的综合综合综合综合综合综合综合既有的综合因素，结肠的发展腺瘤息肉，已建立的结肠癌前体。我们提出了一项基于结肠镜检查的事件病例对照研究，该研究通过前瞻性募集750个事件的结肠息肉病例和750个频率匹配的对照来解决胰岛素抵抗综合症息肉假设。我们将使用血液样本确定候选基因变体和单倍型，相关的生物标志物和胰岛素抵抗综合征相关的血清标记物，并使用问卷收集饮食和生活方式风险因素信息。我们将使用新颖的统计模型分析所得信息，以获得对胰岛素抵抗综合征与结肠息肉之间联系的全面理解。具体而言，我们将1）研究胰岛素抵抗综合征作为整体实体对结肠息肉的影响； 2）检查候选基因和相关的生物标志物在胰岛素-GH-IGF-IRS轴上的影响以及脂肪形成途径对结肠息肉的影响； 3）到评估饮食模式，血糖指数和血糖负荷与结肠息肉的关联； 4）通过查看其对结肠息肉的关节影响，并全面评估这些因素的潜在直接和间接（由胰岛素抵抗综合征介导）对结肠息肉的影响，以综合候选基因，生物标志物和饮食的信息。我们的研究将有助于我们了解与胰岛素抗性综合征途径相关的候选基因和饮食因素如何在结肠腺瘤息肉的病因中起作用。我们的研究可能对针对结肠腺瘤癌症早期的靶向公共卫生预防/干预策略具有深远的影响连续。