Project 01: Understanding Racial Disparity in Endometrial Cancer through Tumor Genomics

项目01：通过肿瘤基因组学了解子宫内膜癌的种族差异

基本信息

批准号：
10265427
负责人：
Ji-Yong Julie Kim
金额：
$ 21.97万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-17 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10265427
关键词：
Adult Affect Age Bioinformatics Biological Carcinoma Child Clinical Clinical Data Custom Data Death Rate Diagnosis Disease Endometrial Carcinoma Endometrial Neoplasms Etiology Exhibits Gamma synuclein Genomics Histologic Hormones Incidence Investigation Knowledge Malignant Female Reproductive System Neoplasm Malignant Neoplasms Modeling Molecular Operative Surgical Procedures Outcome Pathway interactions Patients Phenotype Pregnancy Prevention strategy Primary Neoplasm Process Progestin Therapy Progestins Prognosis Proto-Oncogene Proteins c-akt Research Resistance Risk Factors Seminal Serous Severities Severity of illness TP53 gene Testing Tumor Tissue Tumor stage Universities Uterus Variant Woman Work advanced disease bioinformatics tool black women cancer genomics design exome sequencing fertility preservation health equity improved individualized medicine inhibitor/antagonist innovation mortality next generation sequencing novel novel marker personalized medicine predictive signature prospective racial difference racial disparity responders and non-responders response survival prediction tool transcriptome sequencing treatment response treatment strategy tumor young woman

项目摘要

Abstract The incidence of endometrial cancer is on the rise each year reaching over 60,000 new cases for 2017. As risk factors remain prevalent in both adults and children, more and more women including those of younger age will develop endometrial cancer. Studies demonstrate an obvious race disparity in endometrial cancer where black women present with more aggressive disease and a higher death rate compared to white women. While reasons for this are multifactorial, the biological etiology remains to be studied. In this project, we will collect endometrial tumors and its associated clinical information from black and white women. Exome sequencing will be performed and along with clinical data, bioinformatics analysis will be done to determine the racial differences in tumor genomics. In addition, it is unknown whether the tumors in black women respond to progestin similarly to white women. This is an important piece of the puzzle as young black women have increased severity of disease than white women. Endometrial tumor spheroids will be used to determine progestin response of the tumors ex vivo and with information from exome sequencing, a predictive signature will be generated, which may or may not be different in black women. Finally, an alternative to progestin therapy will be tested ex vivo as an improvement to progestin therapy. This research will increase our understanding of racial differences in endometrial cancer and their response to existing progestin treatments. The impact of our studies will be significant, as we obtain evidence and design tools to improve progestin therapy in endometrial cancer in both black and white women in a personalized manner. !

抽象的子宫内膜癌的发病率逐年上升，2017 年新增病例超过 60,000 例。危险因素在成人和儿童中仍然普遍存在，越来越多的女性，包括年轻女性年龄增长会患子宫内膜癌。研究表明子宫内膜癌存在明显的种族差异与白人女性相比，黑人女性患有更严重的疾病和更高的死亡率。虽然其原因是多因素的，但其生物学病因仍有待研究。在这个项目中，我们将从黑人和白人妇女那里收集子宫内膜肿瘤及其相关临床信息。外显子组将进行测序，并结合临床数据进行生物信息学分析以确定肿瘤基因组学的种族差异。此外，尚不清楚黑人女性的肿瘤是否对孕激素与白人女性相似。这是年轻黑人女性面临的一个重要难题疾病的严重程度比白人女性更高。子宫内膜肿瘤球体将用于确定肿瘤离体孕激素反应以及外显子组测序信息（预测特征）将会产生，这在黑人女性中可能有所不同，也可能没有不同。最后，孕激素的替代品该疗法将作为孕激素疗法的改进进行离体测试。这项研究将增加我们了解子宫内膜癌的种族差异及其对现有孕激素的反应治疗。我们的研究的影响将是巨大的，因为我们获得证据并设计工具来改进以个性化方式对黑人和白人女性子宫内膜癌进行孕激素治疗。！