Epigenomic Markers of HNSCC Survival Across Ethnic Groups

各族裔 HNSCC 存活的表观基因组标记

基本信息

批准号：
8534458
负责人：
Rafael Guerrero-Preston
金额：
$ 13.61万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-22 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8534458
关键词：
Address African American Bioinformatics Biological Biological Markers Blood Cells Case Series Case-Control Studies Cataloging Catalogs Chromosomal Duplication Chromosome Deletion Clinical Clinical Management Cohort Studies Communities DNA DNA Methylation Data Data Set Databases Diagnosis Disease-Free Survival Early Diagnosis Eastern Cooperative Oncology Group Epigenetic Process Ethnic group Funding Opportunities Genes Genetic Genomics Goals HOXA9 gene Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Healthcare Systems High Prevalence Hypermethylation Latino Loss of Heterozygosity Malignant Neoplasms Malignant neoplasm of cervix uteri Mentored Research Scientist Development Award Mentorship Methylation Mission Mutation National Cancer Institute Ontology Operative Surgical Procedures Oral Oral cavity Oral mucous membrane structure Otolaryngology Outcome Pathogenesis Pathway interactions Patients Pharyngeal structure Postoperative Period Prevalence Primary carcinoma of the liver cells Puerto Rican Puerto Rico Race Radiation Therapy Oncology Group Recurrence Relative (related person)Research Design Research Personnel Risk Saliva Salivary Sampling Smoking Solid Specimen Staging Surgical margins Survival Rate TP53 gene Testing Time Tissue Sample Tissues Training Tumor Tissue United States anticancer research base cancer health disparity cohort epigenomics follow-up genome-wide improved instructor male malignant mouth neoplasm malignant oropharynx neoplasm medical schools men mortality novel outcome forecast promoter repository research facility response tumor

项目摘要

Project Summary This is a K01 application submitted by Dr. Rafael Guerrero-Preston in response to the funding opportunity announcement "NCI Mentored Research Scientist Development Award to Promote Diversity (K01)" - PAR-09- 052. Rafael, born and raised in Puerto Rico, is currently appointed as an Instructor at the Head and Neck Cancer Research Division of the Department of Otolaryngology at Johns Hopkins School of Medicine. Rafael's short term goals are to examine global, genome-wide and gene-specific epigenomic alterations in tumors that disproportionally burden African American and Latino communities: hepatocellular carcinoma, cervical cancer and head and neck cancers. Dr Guerrero-Preston's long-term goals are: to develop epigenomic biomarkers to improve Head and Neck Cancer (HNSCC) early detection and clinical management; and to contribute to the reduction of survival disparities in oral and oropharyngeal cancer. The proposed K01 project addresses two objectives relevant to the National Cancer Institute mission: to train culturally diverse cancer researchers; and to eliminate cancer health disparities. The overall HNSCC survival rates for African American patients in the United States has remained close to 20% higher than Whites for more than 30 years, but the biological basis for this disparity is poorly understood. A two-stage epigenomic study design is proposed to test the hypothesis that epigenetic alterations contribute to ethnic disparities in HNSCC survival by examining the following aims: Specific Aim 1: a) To assess differences of global DNA methylation across ethnic groups in tumor-surgical margins pairs of HNSCC patients (n=500); b) To quantify NID2 and HOXA9 differential methylation across ethnic groups in tumor-surgical margins pairs of HNSCC patients (n=500); c) To evaluate the association between differential methylation in tumor-surgical margin pairs, TP53 mutation status, and clinical outcome, including local recurrence and survival across ethnic groups. Specific Aim 2: a) To assess differences of global DNA methylation across ethnic groups in tumor tissue from HNSCC cases (n=300) and normal oral mucosa controls (n=300); b) To quantify NID2 and HOXA9 differential methylation across ethnic groups in tumor tissue from HNSCC cases (n=300) and normal oral mucosa controls (n=300); c) To evaluate the association between differential methylation in tissue and clinical outcome, including local recurrence and survival across ethnic groups. This K01 project strengths are multiple: mentorship by two world leaders in HNSCC genomics, David Sidransky and Wayne Koch; solid institutional support; use of world class research facilities in Johns Hopkins School of Medicine; and access to well characterized sample repositories - the ECOG E4393/RTOG 9614 study, a large multi-institutional head and neck cancer tumor-surgical margin study cohort with abundant outcome data; and a retrospective case-control study from samples stored by the Johns Hopkins Head and Neck Cancer SPORE

项目摘要这是Rafael Guerrero Preston博士提交的K01申请，以回应资金机会公告“ NCI指导了促进多样性的研究科学家发展奖（K01）” - PAR-09-- 052。拉斐尔（Rafael）在波多黎各出生和长大，目前被任命为头颈部的讲师约翰·霍普金斯医学院耳鼻喉科科癌症研究部。拉斐尔的短期目标是检查全球，全基因组和基因特异性表观基因组学的改变，不成比例的非裔美国人和拉丁裔社区：肝细胞癌，宫颈癌以及头部和颈部癌症。 Guerrero-Preston博士的长期目标是：开发表观基因组生物标志物改善头颈癌（HNSCC）早期检测和临床管理；并为口腔和口咽癌中生存差异的降低。拟议的K01项目解决了两个与国家癌症研究所任务相关的目标：培训文化多样的癌症研究人员；和消除癌症健康差异。非裔美国人患者的HNSCC总体生存率在30多年来，美国一直比白人高20％，但生物学基础因为这种差距很熟悉。提出了两级表观基因组研究设计来检验假设这种表观遗传变化通过检查以下目的而导致HNSCC生存的种族差异：特定目的1：a）评估肿瘤外科手术中种族之间全球DNA甲基化的差异 HNSCC患者的边缘对（n = 500）； b）量化NID2和HOXA9差异甲基化 HNSCC患者的肿瘤手术边缘对中的种族群体（n = 500）； c）评估关联在肿瘤手术边缘对中的差异甲基化，TP53突变状态和临床结果之间包括跨种族的当地复发和生存。特定目的2：a）评估肿瘤组织中各个种族群体中全球DNA甲基化的差异 HNSCC病例（n = 300）和正常的口服粘膜对照（n = 300）; b）量化NID2和HOXA9差异 HNSCC病例（n = 300）和正常口服粘膜对照的肿瘤组织中跨种族的甲基化（n = 300）; c）评估组织中差异甲基化与临床结果之间的关联，包括跨种族的当地复发和生存。这个K01项目优势是多重的：HNSCC基因组学中两个世界领导人的指导，大卫 Sidransky和Wayne Koch；可靠的机构支持；约翰·霍普金斯（Johns Hopkins）的世界一流研究设施的使用医学院；并访问良好的样品存储库-ECOG E4393/RTOG 9614 研究，大型多机构的头部和颈癌肿瘤手术边缘研究队列与丰富结果数据；以及来自约翰·霍普金斯（Johns Hopkins Head）和颈部癌孢子