Characterizing genomic risk factors of lung cancers in Native Hawaiians

肺癌是美国第二常见的癌症，也是与癌症相关的主要原因 死亡。肺癌发病率和预后的显著差异是这种疾病的特点 在不同族裔和种族人群中的表现。已经发现，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，存活率最低 结果与其他人群相比。种族和民族的影响在相对较低的情况下更加明显 吸烟的程度。在考虑了已知的肺癌风险因素后，NH和AAS仍处于最高风险 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 未知因素是发生在NH/PI社区的肿瘤的分子图谱。在过去的十年里， 大规模的肺癌基因组研究发现，肺癌驱动因素突变基因存在明显的种族差异。 然而，NHS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。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 来自NH/PI肺癌患者，尽管了解DNA甲基化如何变化的重要性 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肺癌患者健康差距的主要因素，我们建议 研究目的：1.研究NH患者肺癌的基因组图谱。2.进行表观基因组学 非霍奇金淋巴瘤患者肺癌组织的分析。3.确定NH特有的基因组和表观基因组危险因素 通过将NH的图谱与发表的来自其他国家的基因组和表观基因组数据进行比较，发现肺癌 种族/民族人口。这个项目有可能转化为改进的肺癌筛查， 在NH和其他人群中进行精准预防和治疗干预。这个项目也会对我们有所帮助， 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的社区工作人员，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。该实用程序 在这些基础基因组技术中，对在任何人类身上进行生物医学研究都是非常有用的 疾病。

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.