Epigenomic Markers of HNSCC Survival Across Ethnic Groups

各族裔 HNSCC 存活的表观基因组标记

• 批准号: 8922403
• 负责人: Rafael Guerrero-Preston
• 金额: $ 12.16万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 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/8922403
• 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

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

项目概要 这是 Rafael Guerrero-Preston 博士针对资助机会提交的 K01 申请 公告“NCI 指导研究科学家促进多样性发展奖 (K01)”- PAR-09- 052.拉斐尔，在波多黎各出生和长大，目前被任命为头颈教练 约翰霍普金斯大学医学院耳鼻喉科癌症研究部。拉斐尔的 短期目标是检查肿瘤中的全局、全基因组和基因特异性表观基因组改变， 给非裔美国人和拉丁裔社区带来不成比例的负担：肝细胞癌、宫颈癌 以及头颈癌。 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) 的早期检测和临床管理；并为 减少口腔癌和口咽癌的生存差异。拟议的 K01 项目解决了两个问题 与国家癌症研究所使命相关的目标：培训文化多元化的癌症研究人员；和 消除癌症健康差异。非洲裔美国患者 HNSCC 的总体生存率 美国30多年来一直比白人高出近20%，但生物学基础 因为人们对这种差异知之甚少。提出了两阶段表观基因组研究设计来检验该假设 通过检查以下目标，表观遗传改变会导致 HNSCC 生存的种族差异： 具体目标 1：a) 评估肿瘤手术中不同种族群体的总体 DNA 甲基化差异 HNSCC 患者的边缘对 (n=500)； b) 量化 NID2 和 HOXA9 差异甲基化 HNSCC 患者肿瘤-手术切缘对中的种族群体 (n=500)； c) 评估关联 肿瘤-手术切缘对的差异甲基化、TP53突变状态和临床结果之间， 包括跨种族的局部复发和生存。 具体目标 2：a) 评估来自不同种族群体的肿瘤组织中总体 DNA 甲基化的差异 HNSCC 病例 (n=300) 和正常口腔粘膜对照 (n=300)； b) 量化 NID2 和 HOXA9 差异 HNSCC 病例 (n=300) 和正常口腔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， 包括跨种族的局部复发和生存。 这个 K01 项目的优势是多方面的：由 HNSCC 基因组学领域的两位世界领袖 David 提供指导 西德兰斯基和韦恩·科赫；坚实的制度支持；使用约翰·霍普金斯大学世界一流的研究设施 医学院；并访问特征明确的样本存储库 - ECOG E4393/RTOG 9614 研究，一个大型多机构头颈癌肿瘤手术切缘研究队列，具有丰富的 结果数据；以及对约翰·霍普金斯大学校长储存的样本进行的回顾性病例对照研究 颈部癌孢子

项目成果

Prenatal exposure to tobacco smoke leads to increased mitochondrial DNA content in umbilical cord serum associated to reduced gestational age.

• DOI: 10.1080/09603123.2016.1268677
• 发表时间: 2017-03
• 期刊: International journal of environmental health research
• 影响因子: 3.2
• 作者: Pirini F;Goldman LR;Soudry E;Halden RU;Witter F;Sidransky D;Guerrero-Preston R
• 通讯作者: Guerrero-Preston R

Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy.

• DOI: 10.1038/bjc.2011.386
• 发表时间: 2011-10-25
• 期刊: BRITISH JOURNAL OF CANCER
• 影响因子: 8.8
• 作者: Keidar, M.;Walk, R.;Shashurin, A.;Srinivasan, P.;Sandler, A.;Dasgupta, S.;Ravi, R.;Guerrero-Preston, R.;Trink, B.
• 通讯作者: Trink, B.