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

• 批准号: 7545805
• 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
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7545805
• 关键词: Aberrant crypt foci; Acetylation; Adult; Affect; Age; American; Asians; Azoxymethane; Biological Markers; 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; DNA Microarray format; Data; Deoxycytidine; Deoxyguanosine; Development; Diet; Diet Monitoring; Dietary Component; Dietary Factors; Dietary intake; Dose; Early Diagnosis; Elderly; Electrospray Ionization; Environmental Risk Factor; Epigenetic Process; Epithelium; Experimental Designs; Exposure to; Funding Mechanisms; Future; Gene Targeting; Generations; Genes; Genistein; Genome; Genus Cola; Health; Histone H3; Histones; 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; Title; Translational Research; United States; WNT Signaling Pathway; Week; Work; base; cancer diagnosis; cancer prevention; chromatin immunoprecipitation; demethylation; design; feeding; food consumption; improved; malignant breast neoplasm; outcome forecast; programs; promoter; protective effect; research study; soy; tandem mass spectrometry; trend; tumorigenesis

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）：结肠癌是美国最常见的癌症之一。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和发展密切相关。大豆食品和大豆生物活性成分与大量食用大豆食品的人群中结肠癌发病率较低有关。然而，大豆制品和大豆生物活性成分发挥抗癌作用的机制仍存在争议。由于缺乏关于大豆食品预防癌症潜力机制的科学证据，因此没有针对美国人食用大豆食品的营养建议。基于目前对结肠癌的认识和大豆食品有益作用的初步数据，本研究将验证膳食大豆通过表观遗传机制调节结肠癌发展的假设。一个多代暴露模型将用于大豆食品在后代大鼠结肠中的表观遗传编程。利用电喷雾电离质谱、CpG岛甲基化分析和染色质免疫沉淀等技术，结合途径特异性微阵列，本研究的具体目的包括：1)研究大豆喂养后代后的表观遗传景观；2)鉴定WNT信号通路上的特定基因，这些基因通过代大豆饮食进行表观遗传修饰；3)监测暴露于大豆食品的后代在以后的生活中患结肠癌的保护。本课题的研究结果将进一步加深我们对大豆制品在表观遗传学水平上的抗癌机制的认识，并为进一步研究大豆食品和结肠癌预防提供实验设计依据。本课题的研究结果将在表观遗传水平上提高我们对豆制品抗癌机制的认识，并为豆制品与结肠癌预防的进一步研究提供实验设计依据。获得的数据将促进未来将表观遗传特征作为早期癌症检测的分子标记的转化研究。