Incorporating intermediate biomarkers of folate with colorectal cancer

将叶酸中间生物标志物与结直肠癌结合起来

• 批准号: 8107721
• 负责人: David V Conti
• 金额: $ 24.29万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-07 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8107721
• 关键词: Biological Markers; Boxing; Candidate Disease Gene; Carbon; Colon; Colorectal; Colorectal Cancer; Complex; Creatinine; DNA Methylation; Data; Disease; Disease Association; Disease Pathway; Environment; Folate; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Homocysteine; Homocystine; Individual; Interdisciplinary Study; Joints; Link; Lymphocyte; MTHFR gene; Measurement; Measures; Metabolism; Methionine; Methylmalonic Acid; Modeling; Molecular Epidemiology; Parents; Pathway interactions; Peripheral Blood Lymphocyte; Plasma; Population; Process; Research Infrastructure; Riboflavin; Role; Sampling; Scanning; Siblings; Single Nucleotide Polymorphism; Statistical Methods; Statistical Models; System; Testing; Variant; Work; base; carcinogenesis; case control; colon cancer family registry; design; epidemiology study; folic acid metabolism; gene interaction; genetic association; genetic epidemiology; genome wide association study; genome-wide; innovation; insight; malonic acid; methionine methyl ester; novel

DESCRIPTION (provided by applicant): "Incorporating intermediate biomarkers of folate with colorectal cancer" The goal of this proposal is to measure intermediate biomarkers and to evaluate these with statistical methods designed to elucidate the underlying etiologic mechanism of colorectal cancer. The proposal leverages existing genetic data from studies conducted within the Colon Cancer Family Registry (Colon CFR), an NCI-supported consortium initiated in 1997 and dedicated to the establishment of a comprehensive collaborative infrastructure for interdisciplinary studies in the genetics and genetic epidemiology of colorectal cancer. The subjects include 1,531 controls genotyped in a candidate gene study of FOCM pathway genes (RO1CA112237), and 999 controls genotyped in a genome wide association study of colon CFR cases (U01CA122839). In these subjects, we will evaluate plasma measures within one carbon metabolism (plasma folate, vitamins B2, B6, B12, methionine, methyl malonic acid, creatinine, plasma total Hcy (tHcy), and DNA methylation in circulating lymphocytes (PBL)). In addition, we build upon our previous work in developing statistical methods for modeling genetic associations in putative disease pathways. These models integrate various levels of data, e.g. genotypes, gene expression, biomarkers, and exogenous exposures, with prior information to build more comprehensive statistical models for better prioritization, estimation, and characterization of genetic effects. PUBLIC HEALTH RELEVANCE: The overall goal of this proposal is to gain further insight into the underlying etiologic mechanism of colorectal cancer. We will accomplish this by first measuring intermediate biomarkers relevant to folate associated one- carbon metabolism in subjects with existing genotype data from a related candidate gene pathway-based and genome-wide association studies (GWAS). Then using novel statistical methods, we will investigate SNP- biomarker, SNP-disease, and pathway-disease associations to provide more insight into the complex effects of folate on the colorectal carcinogenic process.

描述（由申请人提供）：“将叶酸的中间生物标志物与结直肠癌结合在一起”，该提案的目的是测量中间生物标志物，并使用旨在阐明结直肠癌的潜在病因机制的统计方法来评估它们。该提案利用了在1997年启动的NCI支持的财团（COLON CFR）中进行的研究（COLON CFR）进行的现有遗传数据，该联盟致力于在遗传学和遗传学的色素科学中建立全面的协作基础设施，以建立跨学科研究的全面协作基础架构。这些受试者包括1,531个对照基因在focm途径基因研究（RO1CA112237）的基因研究中，以及999对照在结肠CFR病例的基因组广泛关联研究（U01CA1CA122839）中对基因分型的。在这些受试者中，我们将评估一种碳代谢（血浆叶酸，维生素B2，B6，B12，蛋氨酸，甲基丙二酸，肌酐，血浆总HCY（THCY）和DNA甲基化（循环淋巴细胞（PBL）））的血浆测量。此外，我们基于以前在开发统计方法来建模推定疾病途径中的遗传关联的工作。这些模型集成了各种级别的数据，例如基因型，基因表达，生物标志物和外源性暴露，并具有先验信息，以建立更全面的统计模型，以更好地确定遗传效应的优先次序，估计和表征。 公共卫生相关性：该提案的总体目标是进一步了解结直肠癌的潜在病因机制。我们将通过首先测量与叶酸相关的单碳代谢相关的中间生物标志物与来自相关候选基因途径和全基因组全基因组关联研究（GWAS）的现有基因型数据相关的中间生物标志物。然后，我们将使用新颖的统计方法研究SNP生物标志物，SNP-疾病和途径 - 疾病酶关联，以更深入地了解叶酸对结直肠癌过程的复杂作用。