GENETIC DISSECTION OF INSULIN RESISTANCE IN CANCER AND METABOLIC FUNCTION

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 在过去的几年里，像癌症这样的复杂疾病的遗传学研究越来越受到关注，并且随着我们发现几种常见特征的可能共同代谢途径而变得越来越重要。 到目前为止，这种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性/保护性基因型的基因座的能力最多限于5-10厘摩（cM）的区域。 在开发更复杂的分子工具来研究基因组的同时，越来越多的证据已经收集到导致癌症发展和生存率下降的风险因素。 肥胖和代谢功能障碍一直在这个列表的顶部。 事实上，过去30年来肥胖症和代谢功能障碍的普遍增加（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。本研究评估了与癌症有关的代谢途径指标之间的关系，包括胰岛素抵抗（空腹和葡萄糖负荷后的胰岛素和葡萄糖水平）和胰岛素样生长因子1（IGF 1）的候选基因区域。本研究还评估了潜在的遗传变异作为与癌症共病的性状变异的来源。 我们已经完成了一个大型家系（1400人）中IGF水平的生物标志物测定。 我们对IGF 1、IGFBP 1和IGFBP 3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.