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Effects of Generational Exposure of Soy Diets on Epigenetic Landscape in Colon Ca

大豆饮食的世代暴露对结肠癌表观遗传景观的影响

基本信息

批准号：
7640717
负责人：
Hong Chen
金额：
$ 7.42万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7640717
关键词：
Aberrant crypt foci Acetylation Adult Affect Age American Asians Azoxymethane Cancerous Cells Colon Colon Carcinoma Colonic Neoplasms Colorectal Cancer Colorectal Neoplasms Complex Country Coupled CpG Islands CpG dinucleotide Custom Cytidine DNA DNA Methylation DNA Microarray Chip Data Deoxycytidine Deoxyguanosine Development Diet Diet Monitoring Dietary Component Dietary Factors Dietary intake Dose Early Diagnosis Elderly Electrospray Ionization Environmental Risk Factor Epidemiology Epigenetic Process Epithelium Experimental Designs Exposure to Funding Mechanisms Future Gene Targeting Generations Genes Genistein Health Histone H3 Human Hypermethylation Incidence Intake Investigation Knowledge Length Link Liquid Chromatography Malignant Neoplasms Malignant neoplasm of prostate Maternal Exposure Methylation Modeling Modification Monitor Mus Nutritional Pathway interactions Phytoestrogens Play Population Predisposition Process Promoter Regions Publishing Rattus Recommendation Research Role Screening for cancer Soy Foods Spectrometry, Mass, Electrospray Ionization Surveys Techniques Testing Time Translational Research United States WNT Signaling Pathway Work base cancer diagnosis cancer prevention chromatin immunoprecipitation demethylation design feeding food consumption genome-wide histone modification improved malignant breast neoplasm molecular marker offspring outcome forecast programs promoter protective effect research study soy tandem mass spectrometry trend tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Colon cancer is one of the most frequently diagnosed cancers in the United States. Poor prognosis also makes it one of the deadliest cancers. Dietary factors are closely associated with tumorigenesis and development of colon cancer. Soy foods and soy bioactive components have been linked to lower colon cancer incidence in populations consuming large quantity of soy foods. However there are controversies and mechanisms by which soy products and soy bioactive components exert anticancer effects remain unknown. Because of lack of scientific evidence on the mechanisms of soy foods' cancer prevention potentials, there are no nutritional recommendations regarding soy food consumption made to Americans. Based on current knowledge of colon cancer and preliminary data on beneficial actions of soy foods, the present proposal will test the hypothesis that dietary soy modulates colon cancer development through epigenetic mechanisms. A multi-generational exposure model will be used for epigenetic programming by soy foods in colon of offspring rats. Using techniques including electrospray ionization mass spectrometry, methylation analysis of CpG islands and chromatin immunoprecipitation coupled to a pathway-specific microarray, specific aims in this proposal include: 1) to survey epigenetic landscape of offspring after generations of soy feeding; 2) to identify specific genes along the WNT signaling pathway that are modified epigenetically by generational soy diets; and 3) to monitor protection from getting colon cancer in later life of offspring rats after generational exposure to soy foods. Findings from this project will improve our understandings on anticancer mechanisms of soy products at epigenetic level and facilitate future experimental design for further research on soy foods and colon cancer prevention. Narrative of Relevance Findings from this project will improve our understandings on anticancer mechanisms of soy products at epigenetic level and aid future experimental design for further research on soy foods and colon cancer prevention. Data obtained will facilitate translational research in the future for using epigenetic signatures as molecular markers for early cancer detection.

描述（由申请人提供）：结肠癌是美国最常诊断的癌症之一。预后不良也使其成为最致命的癌症之一。饮食因素与结肠癌的发生、发展密切相关。大豆食品和大豆生物活性成分与食用大量大豆食品的人群降低结肠癌发病率有关。然而，存在争议，豆制品和大豆生物活性成分发挥抗癌作用的机制仍不清楚。由于缺乏关于大豆食品预防癌症潜力机制的科学证据，因此没有向美国人提出有关大豆食品消费的营养建议。根据目前对结肠癌的了解和大豆食品有益作用的初步数据，本提案将检验膳食大豆通过表观遗传机制调节结肠癌发展的假设。多代暴露模型将用于子代大鼠结肠中大豆食品的表观遗传编程。该提案的具体目标包括：1）利用电喷雾电离质谱、CpG 岛甲基化分析和染色质免疫沉淀与通路特异性微阵列相结合等技术，调查几代大豆喂养后后代的表观遗传景观； 2) 识别 WNT 信号通路上的特定基因，这些基因被世代大豆饮食进行表观遗传修饰； 3) 监测代代接触大豆食品后的后代大鼠在晚年生活中预防结肠癌的情况。该项目的研究结果将提高我们对大豆制品在表观遗传水平上的抗癌机制的理解，并为未来大豆食品和结肠癌预防的进一步研究的实验设计提供便利。相关性叙述该项目的研究结果将提高我们对表观遗传水平上大豆产品抗癌机制的理解，并有助于未来大豆食品和结肠癌预防进一步研究的实验设计。获得的数据将有助于未来利用表观遗传特征作为早期癌症检测的分子标记的转化研究。