Integrative Modeling of Genetic and Epigenetic Variation in Colorectal Cancer

结直肠癌遗传和表观遗传变异的综合建模

• 批准号: 7891414
• 负责人: Aditi Hazra
• 金额: $ 8.18万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-10 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7891414
• 关键词: Aberrant DNA Methylation; Affect; Alcohols; Architecture; Award; Biological Markers; Blood Cells; CACNA1G gene; CDKN2A gene; Cancer Etiology; Cataloging; Catalogs; Chromatin; Chromatin Structure; Colorectal Cancer; Colorectal Neoplasms; Consumption; CpG Islands; CpG dinucleotide; DNA; DNA Methylation; DNA Methyltransferase; DNA Modification Methylases; DNA Sequence; Data; Development; Diet; Diet Modification; Dietary Factors; Early Diagnosis; Environmental Risk Factor; Epigenetic Process; Event; Folate; Follow-Up Studies; Frequencies; Gene Silencing; Genes; Genetic; Genetic Models; Genetic Transcription; Genetic Variation; Genome; Genomics; Genotype; Goals; Haplotypes; Health; Health Professional; Histones; Hypermethylation; IGF2 gene; IGFBP3 gene; Individual; Intake; Lead; Leukocytes; Long Interspersed Nucleotide Elements; MLH1 gene; Malignant Neoplasms; Measures; Methionine; Methylation; Modeling; Modification; Nurses; Nurses' Health Study; Population Study; Positioning Attribute; Predisposition; Prevention strategy; Promoter Regions; Public Health; Research; Risk; Risk Factors; Sampling; Single Nucleotide Polymorphism; Testing; Tissues; Tumor Tissue; Variant; base; cancer risk; colorectal cancer prevention; cost; dietary constituent; epigenetic variation; epigenomics; genetic variant; genome-wide; indexing; innovation; insight; peripheral blood; promoter; prospective; tumor

DESCRIPTION (provided by applicant): Although preventable through early detection and modification of risk factors, colorectal cancer (CRC) remains a major public health concern. Early epigenetic alterations and consumption of a low-folate diet have been shown to lead to CRC, possibly due to aberrant DNA methylation. However, the propensity for DNA methylation and its association with gene-diet interactions have not been assessed in a study with prospectively collected dietary information. The overall goal of this proposal is to characterize the association between genetic variation and aberrant DNA methylation of genes in 782 CRC cases in the well-annotated prospective Nurses' Health Study and Health Professionals Follow-up Study. The specific aims are well-powered to evaluate the hypothesis that local DNA sequence context may affect local methylation propensity. These data will enhance our understanding of the association of epigenetic events in colorectal cancer etiology.

描述(由申请人提供)： 虽然可以通过早期发现和修改危险因素来预防，但结直肠癌(CRC)仍然是一个主要的公共卫生问题。早期表观遗传学改变和食用低叶酸饮食已被证明导致CRC，可能是由于DNA甲基化异常所致。然而，DNA甲基化的倾向及其与基因-饮食相互作用的关系尚未在一项具有前瞻性收集的饮食信息的研究中进行评估。这项建议的总体目标是在有良好注解的未来护士健康研究和卫生专业人员随访研究中，表征782例结直肠癌病例中基因变异和基因异常DNA甲基化之间的关联。这些特定的目的很好地评估了局部DNA序列背景可能影响局部甲基化倾向的假设。这些数据将加强我们对表观遗传事件与结直肠癌病因学的关系的理解。