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

描述(申请人提供)：结肠癌是美国最常见的癌症之一。预后不良也使它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。在大量食用大豆食品的人群中，大豆食品和大豆活性成分与较低的结肠癌发病率有关。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和机制尚不清楚。由于缺乏关于大豆食品防癌潜力的机制的科学证据，因此没有针对美国人的关于大豆食品消费的营养建议。基于目前对结肠癌的了解和大豆食品有益作用的初步数据，本提案将检验饮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大豆食物在子代大鼠结肠中的表观遗传编程。利用电喷雾电离质谱仪、CpG岛甲基化分析和染色质免疫共沉淀与特定途径微阵列相结合的技术，该建议的具体目标包括：1)调查世代大豆喂养后后代的表观遗传格局；2)确定WNT信号通路上的特定基因，这些基因经过世代大豆饮食的表观遗传修饰；以及3)监测世代大豆饮食对后代大鼠日后患结肠癌的保护作用。本项目的研究结果将在表观遗传水平上提高我们对大豆制品抗癌机制的理解，并为未来大豆食品和结肠癌预防的进一步研究提供实验设计。叙述这一项目的相关发现将在表观遗传水平上提高我们对大豆制品抗癌机制的理解，并为未来大豆食品和结肠癌预防的进一步研究提供实验设计。所获得的数据将有助于未来将表观遗传特征用作早期癌症检测的分子标记的翻译研究。

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.