Insulin Resistance Syndrome Pathway Factors & Colon Poly

模型系统和流行病学研究越来越多的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世界范围内以流行病的速度上升，这使得探索胰岛素抵抗-结肠肿瘤假说成为一个紧迫的优先课题。我们假设胰岛素-生长激素-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（脂联素和过氧化物酶体增殖激活受体- γ）和饮食因素中的候选基因和相关生物标志物可能共同推动胰岛素抵抗综合征的发展，并随后推动结肠的发展

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.