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.

尽管美洲印第安人（AI）部落和社区在种族，语言和文化方面高度多样化，但他们共享的一个不幸的特征是：严重的癌症健康差异。复杂 AI的癌症筛查率不成比例低，获得医疗保健的机会更高，因此在疾病的后期诊断，与美国的任何其他种族和族裔。这些重大癌症健康差异的原因是无疑是多因素。但是，未开发的因素是肿瘤的分子表征人工智能。美洲印第安人和阿拉斯加原住民（AN）在癌症基因组地图集中已经大量研究了项目（TCGA）仅占研究的癌症患者的<0.5％。在近11,000名患者中迄今为止在TCGA中测序，仅将27（0.25％）识别为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，我们将发现新型的体细胞和种系突变，促进癌症的频谱和/或频率的差异突变以及全基因组的突变特征反映了行为和暴露的反映，最终可能是转化为改善美洲印第安人的癌症筛查，预防精度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在西南的AI中显示出很大的差异，包括胃肠道和肝癌（胃，结直肠，胰腺，肝脏，胆囊和胆汁树）；泌尿生殖器癌（肾脏，前列腺癌症）;和其他依赖激素的癌症（乳腺癌，卵巢癌）。我们的具体目的是发展具有文化适当，尊重和值得信赖的手段：1）与美洲印第安人参与（癌症患者）和幸存者）及其部落社区在参与性研究中有关分子表征的研究研究癌症，尤其是专注于在西南部表现出明显差异和结果的癌症部落国家； 2）发现新型的体细胞和种系突变和/或频谱中的差异促进癌症突变的频率和全基因组突变特征反映了特定在美洲印第安人参与者中，相对于其他种族和种族人口的行为和暴露美国和世界； 3）通过这些研究将知识传播给部落参与者和部落理事会，领导人，利益相关者和社区使用独特的参与者和新颖的方式对文化和宗教信仰敏感的视觉艺术和媒体等交流手段实践和承认土著语言和方言，其中许多语言缺乏许多科学的语言和方言癌症，基因，基因组学，突变和DNA等单词和概念的医学术语以及4）（共享通过NCI基因组数据共享与更广泛的科学界的知识，并发布科学结果符合NIH数据共享政策和部落协议。