Characterizing genomic risk factors of lung cancers in Native Hawaiians

夏威夷原住民肺癌基因组风险因素的特征

• 批准号: 10749847
• 负责人: Youping Deng
• 金额: $ 92.81万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749847
• 关键词: Accounting; Address; African American population; Asian population; Behavior; Bioinformatics; Biomedical Research; Cancer Etiology; Cancer Patient; Cells; Cessation of life; Clinical; Communities; Community Workers; Copy Number Polymorphism; DNA; DNA Methylation; DNA sequencing; Data; Data Analyses; Data Science; Development; Disease; Disparity; Epidermal Growth Factor Receptor; Epigenetic Process; Ethnic Origin; Ethnic Population; Formalin; Freezing; Frequencies; Gene Mutation; Genes; Genome; Genomics; Germ-Line Mutation; Hawaiian population; Incidence; International; Latino Population; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Methylation; Modification; Molecular; Molecular Profiling; Mutate; Mutation; Native Hawaiian; Native Hawaiian or Other Pacific Islander; Normal tissue morphology; Outcome; Pacific Islander; Paraffin Embedding; Patients; Population; Population Heterogeneity; Proteomics; Publishing; Race; Research; Research Design; Research Personnel; Risk; Risk Factors; Sampling; Smoking; Somatic Mutation; Technical Expertise; Technology; The Cancer Genome Atlas; Therapeutic Intervention; Tissue Sample; Tissues; Translating; United States; Workforce Development; bisulfite sequencing; cancer genome; cancer genomics; cancer health disparity; cancer immunotherapy; cancer risk; community engagement; comparative; driver mutation; epigenomic profiling; epigenomics; ethnic diversity; exome sequencing; genetic signature; genome sequencing; genome-wide; genomic data; health disparity; high risk; human disease; improved; lung cancer screening; novel; personalized intervention; preventive intervention; profiles in patients; racial disparity; racial diversity; response; sample fixation; skills; student training; survival outcome; tumor; whole genome

Lung cancer is the second most common cancer in the United States and the leading cause of cancer-related deaths. Significant disparities in incidence and outcome of lung cancer characterize the disease’s manifestation among ethnically and racially diverse populations. It has been found that Native Hawaiians (NH), Pacific Islanders (PI), and African Americans (AA) have the highest lung cancer risk and poorest survival outcomes compared to other populations. The influence of race and ethnicity is more evident at relatively low levels of smoking. After accounting for known lung cancer risk factors, NH and AAs remain at highest risk of lung cancer. The cause of these significant lung cancer health disparities is undoubtedly multifactorial. However, an unexplored factor is the molecular profiles of tumors arising in the NH/PI communities. In the past decade, large-scale lung cancer genomic studies have found clear racial disparity for lung cancer driver mutation genes. However, NHs have been strikingly underrepresented in The Cancer Genome Atlas Project (TCGA) and other cancer genome projects. There are almost no NH lung cancer patients included in the previous projects. There have also been no studies to compare DNA methylation changes between tumor and adjacent normal samples from NH/PI lung cancer patients, despite the importance of understanding how DNA methylation changes contribute to NH lung cancer development. To address the critical gap in lung cancer genomics studies and to understand the key factors that contribute to the health disparity of NH/PI lung cancer patients, we propose the following aims: 1. Characterize genomic landscape of lung cancer in NH patients. 2. Perform epigenomic profiling of lung cancer tissues in NH patients. 3. Identify NH specific genomic and epigenomic risk factors of lung cancer by comparing the profiles from NH with the published genomic and epigenomic data from other racial/ethnic populations. This project has the potential to be translated into improved lung cancer screening, precision prevention, and therapeutic intervention in NH and other populations. This project will also help us, via the Genomic Workforce Development Core included in the overall proposal, to train students, researchers, and community workers with genomics and genomic data science skills, such as whole genome sequencing (WGS), whole exome sequencing (WES), Illumina DNA methylation microarray, and whole-genome bisulfite sequencing (WGBS), as well as bioinformatics and data science skills related to the data analyses. The utility of these fundamental genomic technologies, is very useful for conducting biomedical research in any human diseases.

肺癌是美国第二大常见癌症，也是癌症相关疾病的主要原因。 死亡肺癌的发病率和预后的显著差异是该疾病的特征， 在不同民族和种族的人群中表现出来。据发现，夏威夷土著人（NH）， 太平洋岛民（PI）和非洲裔美国人（AA）的肺癌风险最高，生存率最低 与其他人群相比。种族和民族的影响在相对较低的 吸烟水平。在考虑了已知的肺癌风险因素后，NH和AA仍然是肺癌的最高风险。 肺癌 这些显著的肺癌健康差异的原因无疑是多因素的。但安 未探索的因素是NH/PI社区中产生的肿瘤的分子谱。在过去十年中， 大规模的肺癌基因组研究发现，肺癌驱动突变基因存在明显的种族差异。 然而，在癌症基因组图谱项目（TCGA）和其他研究中， 癌症基因组计划在以前的项目中几乎没有NH肺癌患者。那里 也没有研究比较肿瘤和邻近正常样本之间的DNA甲基化变化 从NH/PI肺癌患者，尽管了解DNA甲基化如何改变的重要性， 有助于NH肺癌的发展。为了解决肺癌基因组学研究中的关键空白， 了解导致NH/PI肺癌患者健康差异的关键因素，我们提出 以下目标：1.表征NH患者中肺癌的基因组景观。2.执行表观基因组 NH患者中肺癌组织的分析。3.确定NH特异性基因组和表观基因组风险因素， 肺癌通过比较从NH与其他已发表的基因组和表观基因组数据的配置文件 种族/民族人口。该项目有可能转化为改善肺癌筛查， NH和其他人群的精准预防和治疗干预。这个项目也将帮助我们， 通过整体提案中包含的基因组劳动力发展核心，培训学生，研究人员， 以及具有基因组学和基因组数据科学技能的社区工作者，例如全基因组测序 (WGS)、全外显子组测序（WES）、Illumina DNA甲基化微阵列和全基因组亚硫酸氢盐 测序（WGBS），以及与数据分析相关的生物信息学和数据科学技能。本实用 这些基本的基因组技术，是非常有用的进行生物医学研究，在任何人类 疾病