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: 7723450
• 负责人: Courtney Montgomery
• 金额: $ 0.45万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723450
• 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; IGFBP1 gene; IGFBP3 gene; Individual; Institution; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Insulin-Like Growth-Factor Binding Protein 1; Localized; Malignant Neoplasms; Metabolic; Metabolic Pathway; Modeling; Molecular; Morbidity - disease rate; Obesity; Pathway interactions; Predisposition; Research; Research Personnel; Resources; Risk Factors; SNP genotyping; Somatomedins; Source; United States National Institutes of Health; Variant; cohort; 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 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在过去的几年中，对癌症等复杂疾病的遗传研究引起了人们的关注，并且随着我们发现几种常见特征的常见代谢途径越来越重要。 至此，此类研究的主要工具是链接分析。 然而，连锁分析本地位置可能隔离易感性/保护性基因型的基因座的能力最多仅限于5-10厘米（CM）的区域。 与研究基因组的更复杂的分子工具的开发同时，已经收集了越来越多的证据，这些证据是导致癌症发展和降低生存的危险因素。 肥胖和代谢功能障碍一直处于此列表的顶部。 实际上，在过去30年中，肥胖和代谢功能障碍的流行病（成人增加了一倍，儿童三倍）预示了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（禁食和葡萄糖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（IGF1）。这也评估了潜在的遗传变异作为与癌症的特征变异的潜在遗传变异。 我们已经在大量的血统（1400个个体）中完成了IGF水平的生物标志物测定。 我们在IGF1，IGFBP1和IGFBP3基因中具有基因分型SNP。 这些途径的关联分析和建模目前正在进行中。