Engagement of American Indians of Southwestern Tribal Nations in Cancer Genome Sequencing

西南部落国家的美洲印第安人参与癌症基因组测序

基本信息

批准号：
10759095
负责人：
JEFFREY M. TRENT
金额：
$ 14.5万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-02 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10759095
关键词：
Address Agreement Alaska Native Alcohols American Indians Behavior Belief Biological Biological Markers Breast Cancer Burden Cancer Etiology Cancer Patient Cancer Survivor Characteristics Colorectal Communication Communities DNA Data Commons Development Diagnosis Diet Disease Disparity Environmental Exposure Ethnic Origin Ethnic Population Frequencies Gallbladder Genes Genetic Genome Genomics Germ-Line Mutation Goals Hepatitis Hormones Human Papillomavirus Incidence Indigenous Individual Intervention Kidney Knowledge Language Liver Malignant Neoplasms Malignant neoplasm of gastrointestinal tract Malignant neoplasm of ovary Malignant neoplasm of prostate Medical Metabolism Molecular Mutation Native Hawaiian or Other Pacific Islander Obesity Outcome Pancreas Participant Patients Policies Public Health Publications Religious Belief Research Risk Behaviors Screening for cancer Somatic Mutation Stomach Survival Rate The Cancer Genome Atlas Therapeutic Intervention Tobacco Translating Translations Tribal Council Tribes Trust United States United States National Institutes of Health Urogenital Cancer Vaccination Virus Visual anticancer research biliary tract cancer genome cancer health disparity cancer survival cancer type community engagement data sharing differences in access genome database genome sequencing genome-wide health care availability hepatobiliary cancer improved individualized prevention intravenous drug use mortality novel novel diagnostics patient engagement personalized intervention precision medicine preventive intervention racial population research study screening therapeutically effective tribal Nation tribal community tumor virtual

项目摘要

While American Indian (AI) Tribes and communities are highly diverse in ethnicity, language, and culture, there is one unfortunate characteristic that they share: profound cancer health disparities. Compounded by disproportionately low rates of cancer screening and more limited access to healthcare, AI are more often diagnosed at later stages of disease and have the poorest outcomes in all types of cancer when compared to any other racial and ethnic group in the United States. The cause of these significant cancer health disparities is undoubtedly multifactorial. However, an unexplored factor is the molecular characterization of tumors arising in AI. American Indians and Alaska Natives (AN) have been strikingly understudied in The Cancer Genome Atlas Project (TCGA) and account for only < 0.5% of the cancer patients studied. Of the nearly 11,000 patients sequenced in TCGA to date, only 27 (0.25%) were identified as AI/AN. It is our hypothesis that through appropriate participant and community engagement and comprehensive genomic sequencing, we will discover novel somatic and germline mutations, differences in the spectrum and/or frequency of cancer-promoting mutations, and genome-wide mutational signatures reflective of behaviors and exposures, that can ultimately be translated to improved cancer screening, precision prevention, and therapeutic intervention in American Indian participants and communities. In this application, we will focus on the molecular characterization of cancers which show significant disparities in AI of the Southwest, including gastrointestinal and hepatobiliary cancers (stomach, colorectal, pancreatic, liver, gallbladder and biliary tree); genitourinary cancers (kidney, prostate cancer); and other hormone-dependent cancers (breast, ovarian cancers). Our Specific Aims are to develop culturally-appropriate, respectful, and trusted means to: 1) Engage American Indian participants (cancer patients and survivors) and their Tribal communities in participatory research studies of the molecular characterization of cancer, particularly focusing on cancers that display striking disparities in incidence and outcome in Southwest Tribal Nations; 2) Discover novel somatic and germline mutations and/or differences in the spectrum and frequency of cancer-promoting mutations, and genome-wide mutational signatures reflective of specific behaviors and exposures, in American Indian participants, relative to other racial and ethnic populations in the U.S. and the world; 3) Disseminate knowledge gained through these studies to Tribal participants and Tribal Councils, leaders, stakeholders, and communities using unique means of participant engagement and novel means of communication, such as visual arts and media, that are sensitive to cultural and religious beliefs and practices and that acknowledge the indigenous languages and dialects, many of which lack many scientific and medical terms for words and concepts such as cancer, gene, genomics, mutation, and DNA, and 4) (Share knowledge with the broader scientific community through the NCI Genome Data Commons and publication of scientific results in accordance with NIH Data Sharing Policies and Tribal Agreements.

虽然美洲印第安人 (AI) 部落和社区在种族、语言和文化方面高度多样化，但他们所共有的一个不幸的特征是：巨大的癌症健康差异。复合为癌症筛查率不成比例地低，获得医疗保健的机会也更加有限，人工智能更常见与其他类型的癌症相比，在疾病晚期才被诊断出来，并且在所有类型的癌症中具有最差的结果美国的任何其他种族和族裔群体。这些重大癌症健康差异的原因是无疑是多因素的。然而，一个尚未探索的因素是肿瘤发生的分子特征。人工智能。癌症基因组图谱对美洲印第安人和阿拉斯加原住民 (AN) 的研究明显不足项目 (TCGA) 仅占所研究癌症患者的 < 0.5%。在近 11,000 名患者中迄今为止，在 TCGA 中进行测序时，只有 27 个（0.25%）被鉴定为 AI/AN。我们的假设是通过适当的参与者和社区参与以及全面的基因组测序，我们会发现新的体细胞和种系突变、促癌谱和/或频率的差异突变以及反映行为和暴露的全基因组突变特征，最终可以转化为改善美洲印第安人的癌症筛查、精准预防和治疗干预参与者和社区。在此应用中，我们将重点关注癌症的分子表征西南地区的人工智能存在显着差异，包括胃肠癌和肝胆癌（胃、结直肠、胰腺、肝脏、胆囊和胆管树）；泌尿生殖系统癌症（肾癌、前列腺癌癌症）;和其他激素依赖性癌症（乳腺癌、卵巢癌）。我们的具体目标是发展文化上适当、尊重和值得信赖的方式： 1) 让美洲印第安人参与者（癌症患者和幸存者）及其部落社区参与分子特征研究癌症，特别关注西南地区发病率和结果存在显着差异的癌症部落国家； 2) 发现新的体细胞和种系突变和/或谱系差异促癌突变的频率，以及反映特定基因的全基因组突变特征美洲印第安人参与者相对于其他种族和民族人口的行为和暴露美国和世界； 3) 将通过这些研究获得的知识传播给部落参与者和部落理事会、领导者、利益相关者和社区使用独特的参与者参与方式和新颖的方式对文化和宗教信仰敏感的交流方式，例如视觉艺术和媒体，做法并承认土著语言和方言，其中许多语言和方言缺乏许多科学和知识癌症、基因、基因组学、突变和 DNA 等单词和概念的医学术语，以及 4)（分享通过 NCI 基因组数据共享和出版，让更广泛的科学界了解知识根据 NIH 数据共享政策和部落协议的科学结果。