GENETIC DISSECTION OF INSULIN RESISTANCE IN CANCER AND METABOLIC FUNCTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在过去的几年里，对癌症等复杂疾病的遗传学研究得到了越来越多的关注，随着我们发现几个共同特征可能的共同代谢途径，这一研究变得越来越重要。到目前为止，这类研究的主要遗传工具是连锁分析。然而，连锁分析定位可能分离易感/保护性基因型的基因座的能力最多仅限于5-10厘米器官(Cm)的区域。在开发更复杂的分子工具来研究基因组的同时，收集了越来越多关于导致癌症发展和存活率下降的风险因素的证据。肥胖和代谢障碍一直位居榜首。事实上，在过去30年里，肥胖和代谢功能障碍的流行增加(成人增加一倍，儿童增加两倍)预示着癌症发病率和死亡率的大幅增加。这项研究评估了与癌症有关的代谢途径指数，包括胰岛素抵抗(空腹和糖负荷后胰岛素和葡萄糖水平)与胰岛素样生长因子1(IGF1)候选基因区域之间的关系。该研究还评估了潜在的遗传变异作为与癌症共存的特征变异的来源。我们已经完成了对一大群家系(1400人)中IGF水平的生物标志物分析。我们对IGF1、IGFBP1和IGFBP3基因的SNPs进行了基因分型。目前正在对这些途径进行关联分析和建模。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The genetic study of complex diseases like cancer has gained increased attention over the past several years and has become more and more important as we discover likely common metabolic pathways for several common traits. The primary genetic tool for such studies, to this point, has been linkage analysis. However, the ability of linkage analysis to localize a locus potentially segregating for susceptibility/protective genotypes is limited to, at best, a region of 5-10 centimorgans (cM). In parallel with the development of more sophisticated molecular tools to investigate the genome, increasing evidence has been collected on risk factors leading to the development and decreased survivorship of cancer. Obesity and metabolic dysfunction have been at the top of this list. In fact, the epidemic increase in obesity and metabolic dysfunction over the last 30 years (doubling in adults and tripling in children) portend a substantial increase in cancer morbidity and mortality. This study assesses the relationship between indices of metabolic pathways implicated in cancer, including insulin resistance (fasting and post glucose load insulin and glucose levels) and the candidate gene region for insulin-like growth factor 1 (IGF1).This study also assesses potential genetic variation as a source of variation in traits comorbid with cancer. We have completed biomarker assays for IGF levels in a large cohort of pedigrees (1400 individuals). We have genotyped SNPs in IGF1, IGFBP1 and IGFBP3 gene. Association analysis and modeling of these pathways is currently underway.