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：
10488638
负责人：
Ji-Yong Julie Kim
金额：
$ 25.23万
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 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10488638
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 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生率每年增加，2017年的新病例超过60,000例。危险因素在成人和儿童中仍然普遍存在，越来越多的女性在内年龄将发展为子宫内膜癌。研究表明，子宫内膜癌的种族差异明显与白人妇女相比，黑人妇女患有更侵略性疾病和更高的死亡率。尽管这样做的原因是多因素的，但生物学病因仍有待研究。在这个项目中，我们将从黑白妇女那里收集子宫内膜肿瘤及其相关的临床信息。外显子将进行测序并与临床数据一起，将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，尚不清楚黑人妇女的肿瘤是否反应孕激素类似于白人妇女。这是一个重要的难题，因为年轻的黑人妇女有疾病严重程度比白人妇女增加。子宫内膜肿瘤球体将用于确定肿瘤的孕激素反应离体和外显子组测序的信息，预测性特征将产生，黑人妇女可能会或可能不会有所不同。最后，替代品的替代品治疗将在体内进行测试，以改善孕激素治疗。这项研究将增加我们的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。当我们获得证据和设计工具以改进的情况下，我们的研究的影响将是重要的黑白妇女的子宫内膜癌中的孕激素治疗以个性化的方式。呢