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 死亡人数。肺癌发病率和结果的显着差异是该疾病的特征 在民族和种族不同的人群中表现出来。研究发现，夏威夷原住民 (NH) 太平洋岛民 (PI) 和非裔美国人 (AA) 的肺癌风险最高，生存率最差 与其他人群相比的结果。种族和族裔的影响在相对较低的情况下更为明显 吸烟程度。考虑到已知的肺癌危险因素后，NH 和 AA 仍然处于最高风险之中 肺癌。 这些显着的肺癌健康差异的原因无疑是多因素的。然而，一个 未探索的因素是 NH/PI 群落中出现的肿瘤的分子特征。在过去的十年里， 大规模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，NH 在癌症基因组图谱计划 (TCGA) 和其他项目中的代表性明显不足。 癌症基因组计划。之前的项目中几乎没有纳入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 尽管了解 DNA 甲基化如何变化很重要，但来自 NH/PI 肺癌患者 有助于 NH 肺癌的发展。解决肺癌基因组学研究中的关键差距并 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. 描述 NH 患者肺癌的基因组图谱。 2. 进行表观基因组学 NH 患者肺癌组织的分析。 3. 确定 NH 特定基因组和表观基因组风险因素 通过将 NH 的概况与其他国家已发表的基因组和表观基因组数据进行比较，得出肺癌 种族/族裔人口。该项目有潜力转化为改进的肺癌筛查， 对新罕布什尔州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， 通过总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（例如全基因组测序）的社区工作者 (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。实用性 这些基本基因组技术对于在任何人类中进行生物医学研究非常有用 疾病。