Insulin Resistance Syndrome Pathway Factors & Colon Poly

越来越多的模型系统和流行病学研究证据支持长期能量失衡导致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型糖尿病的发病率在全球范围内以流行病的速度上升，这一事实使得胰岛素抵抗-结肠肿瘤假说的探索成为一个紧迫的优先事项。我们假设，胰岛素-生长因子-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（脂联素和过氧化物酶体增殖物激活受体-γ）和饮食因素中的候选基因和相关生物标志物可能共同驱动胰岛素抵抗综合征的发展，并随后导致结肠癌的发展。 腺瘤性息肉，结肠癌的前兆。我们提出了一项基于筛查的结肠镜检查事件病例对照研究，通过前瞻性招募750例结肠息肉事件病例和750例频率匹配的对照，来解决胰岛素抵抗综合征-结肠息肉假设。我们将使用血液样本确定候选基因变异和单倍型、相关生物标志物和胰岛素抵抗综合征相关血清标志物，并使用问卷调查收集饮食和生活方式风险因素信息。我们将使用新的统计模型分析所得信息，以全面了解胰岛素抵抗综合征和结肠息肉之间的联系。具体而言，我们将1）研究胰岛素抵抗综合征作为结肠息肉的一个整体的影响; 2）研究胰岛素-GH-IGF-IRS轴和脂肪生成途径中的候选基因和相关生物标志物对结肠息肉的影响; 3）研究胰岛素抵抗综合征对结肠息肉的影响。 评估饮食模式、血糖指数和血糖负荷与结肠息肉的关联; 4）通过观察候选基因、生物标志物和饮食对结肠息肉的联合作用来综合它们的信息，并综合评估这些因素对结肠息肉的潜在直接和间接（由胰岛素抵抗综合征介导）影响。 我们的研究将有助于我们了解胰岛素抵抗综合征途径相关的候选基因和饮食因素如何在结肠腺瘤性息肉的病因学中协同作用。我们的研究可能对针对结肠腺瘤-癌症早期阶段的公共卫生预防/干预策略具有深远的意义 连续体

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.