GENETIC DISSECTION OF INSULIN RESISTANCE IN CANCER AND METABOLIC FUNCTION

癌症中胰岛素抵抗和代谢功能的基因剖析

• 批准号: 7956485
• 负责人: Courtney Montgomery
• 金额: $ 0.48万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956485
• 关键词: Adult; Attention; Biological Assay; Biological Markers; Cancer Survivorship; Candidate Disease Gene; Child; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Dissection; Epidemic; Fasting; Functional disorder; Funding; Genetic; Genetic Variation; Genome; Genotype; Glucose; Grant; Human Genetics; IGFBP1 gene; IGFBP3 gene; Individual; Institution; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Malignant Neoplasms; Metabolic; Metabolic Pathway; Modeling; Molecular; Morbidity - disease rate; Obesity; Pathway interactions; Predisposition; Research; Research Personnel; Resources; Risk Factors; SNP genotyping; Source; United States National Institutes of Health; Variant; cohort; genetic analysis; genetic linkage analysis; genetic pedigree; indexing; mortality; tool; trait

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 癌症等复杂疾病的基因研究在过去几年中受到越来越多的关注，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，此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，越来越多的证据收集到导致癌症发生和生存率降低的风险因素。 肥胖和代谢功能障碍一直位居榜首。 事实上，过去 30 年肥胖和代谢功能障碍的流行增加（成人增加一倍，儿童增加三倍）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标之间的关系，包括胰岛素抵抗（空腹和葡萄糖负荷后胰岛素和葡萄糖水平）与胰岛素样生长因子 1 (IGF1) 的候选基因区域。这项研究还评估了潜在的遗传因素变异是癌症共病性状变异的一个来源。 我们已经完成了一大批家系（1400 名个体）的 IGF 水平生物标志物测定。 我们对 IGF1、IGFBP1 和 IGFBP3 基因中的 S​​NP 进行了基因分型。 这些途径的关联分析和建模目前正在进行中。