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

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。

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.