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

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中结肠癌发病率降低有关。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不清楚，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，美国人没有关于大豆食品消费的营养建议。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，本提案将测试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后代大鼠结肠中大豆食物的表观遗传编程。利用电喷雾质谱、CpG岛甲基化分析和染色质免疫沉淀结合途径特异性微阵列等技术，本研究的具体目标包括：1）调查几代大豆喂养后后代的表观遗传景观; 2）鉴定WNT信号通路中沿着被几代大豆饲料表观遗传修饰的特定基因;和3）监测后代大鼠在世代暴露于大豆食品后在以后的生活中免受结肠癌的保护。本研究的发现将有助于我们在表观遗传学水平上对大豆制品的抗癌机制的理解，并为大豆食品和结肠癌预防的进一步研究提供实验设计。相关性研究结果的叙述将提高我们对大豆制品在表观遗传学水平上的抗癌机制的理解，并为大豆食品和结肠癌预防的进一步研究提供未来的实验设计。所获得的数据将促进未来使用表观遗传标记作为早期癌症检测的分子标记的转化研究。

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.