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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.

虽然美国印第安人(AI)部落和社区在种族、语言和文化上高度多样化，但在是他们共有的一个不幸的特征：严重的癌症健康差异。与之复合癌症筛查率低得不成比例，获得医疗保健的机会更有限，人工智能更经常在疾病的后期被诊断出来，在所有类型的癌症中，与在美国的任何其他种族和民族。这些显著的癌症健康差异的原因是毫无疑问，这是多因素的。然而，一个未被探索的因素是发生在艾。美国印第安人和阿拉斯加原住民(AN)在癌症基因组图谱中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名患者中到目前为止，经TCGA测序，仅有27例(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，我们将发现新的体细胞和生殖系突变，致癌光谱和/或频率的差异突变，以及反映行为和暴露的全基因组突变签名，最终可能是转化为改善美洲印第安人的癌症筛查、精确预防和治疗干预参与者和社区。在这项应用中，我们将重点研究癌症的分子特征这表明西南地区的人工智能存在显著差异，包括胃肠癌和肝胆癌 (胃癌、结直肠癌、胰腺癌、肝癌、胆囊癌和胆道癌)；泌尿生殖道癌(肾癌、前列腺癌) 癌症)；以及其他依赖激素的癌症(乳腺癌、卵巢癌)。我们的具体目标是发展文化上合适、尊重和信任的方式：1)让美国印第安人参与者(癌症患者)参与进来和幸存者)和他们的部落社区参与对生物多样性的分子特征的研究癌症，特别是在西南地区发病率和预后存在显著差异的癌症部落民族；2)发现新的体细胞和生殖系突变和/或光谱差异致癌突变的频率，以及反映特定基因突变的全基因组突变特征与其他种族和民族人群相比，美国印第安人参与者的行为和暴露美国和世界；3)向部落参与者和部落传播通过这些研究获得的知识议会、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对文化和宗教信仰敏感的传播手段，如视觉艺术和媒体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医学术语和概念，如癌症、基因、基因组学、突变和DNA，以及4)(分享通过NCI基因组数据共享和出版符合NIH数据共享政策和部落协议的科学结果。