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

• 批准号: 10251929
• 负责人: JEFFREY M. TRENT
• 金额: $ 367.79万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-02 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10251929
• 关键词: Address; Agreement; Alaska Native; Alcohols; American Indians; Arts; Behavior; Belief; Biological; Breast; Cancer Burden; Cancer Etiology; Cancer Patient; Cancer Survivor; Characteristics; Colorectal; Communication; Communities; DNA; Data Commons; Development; Diagnosis; Diet; Disease; Environmental Exposure; Ethnic Origin; Ethnic group; Frequencies; Gallbladder; 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; Obesity; Oncogenes; Outcome; Pacific Islander; Pancreas; Participant; Patients; Policies; Public Health; Publications; Race; Religious Belief; Research; Risk Behaviors; Screening for cancer; Somatic Mutation; Stomach; Survival Rate; The Cancer Genome Atlas; Therapeutic Intervention; Time; 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; health disparity; hepatobiliary cancer; improved; individualized prevention; intravenous drug use; mortality; novel; novel diagnostics; patient engagement; precision medicine; preventive intervention; racial population; research study; screening; targeted biomarker; therapeutically effective; tribal Nation; tribal community; tumor; virtual

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 显示出西南地区人工智能的显着差异，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。