Project 1: Viewing Native American Cervical Cancer Disparities through the Lens of the Vaginal Microbiome

项目摘要/摘要：项目1 从美国本土人的视角看宫颈癌的差异 阴道微生物群 在美国，每年约有12,900例宫颈癌被诊断出来，每年的死亡率 超过4000人。根据印第安人健康服务机构1999-2009年的数据，美国印第安人/阿拉斯加原住民 (AI/AN)妇女的宫颈癌发病率和相关死亡率大约高出两倍 而不是白人女性。宫颈癌的不平等主要归因于缺乏筛查和不平等。 获得医疗保健；然而，其他因素，如高危人乳头瘤病毒的高流行率 AI/AN中的(HrHPV)女性也可能是贡献者。阴道微生物区系(VMB)的某些成分， 最近发现，定居在阴道中的微生物与宫颈发育有关。 癌症，并被观察到在白人女性和西班牙裔女性之间存在差异，在这种情况下，宫颈癌 也有报道称，利率存在差异。这项建议的目标是解决VMB的作用和 炎症在AI/AN妇女宫颈癌发病机制中的作用中心假设是VMB 作为女性生殖道(FRT)粘膜炎症的关键调节因子，可能会影响 癌前病变的发展和向侵袭性疾病的进展。为了检验这一假设，有两个例子 具体目标将在一个涉及100名人工智能/人工智能妇女和100名非人工智能/人工智能控制者的小型试点项目中得到解决 (每组50例健康妇女和50例宫颈发育不良妇女)。预计结果将是 这项研究将为支持一个更大的项目提供框架和初步证据。在目标1中，一个文化上的 将为AI/AN妇女制定和实施敏感的阴道样本采集方案 与亚利桑那州弗拉格斯塔夫的美洲原住民社区行动(NACA)诊所合作。随后，在 目的2计算阴道微生物群组成、宿主免疫活性、HPV之间的相关性 基因分型和乳酸菌丰度在AI/AN妇女和非AI/AN妇女中的分布 首次探讨这些因素与宫颈异型增生的关系及是否存在差异 存在于AI/AN和非AI/AN女性的VMB中。影响：这项研究还将为培训提供背景 北亚利桑那大学、亚利桑那大学和亚利桑那州立大学切割专业的AI/AN学生 生物医学研究的前沿，将是为人工智能/AN带来基于基因组学的健康进步的一步 社区。

PROJECT SUMMARY/ABSTRACT: PROJECT 1 VIEWING NATIVE AMERICAN CERVICAL CANCER DISPARITIES THROUGH THE LENS OF THE VAGINAL MICROBIOME In the U.S., approximately 12,900 cases of cervical cancer are diagnosed each year, and annual mortality exceeds 4,000. According to Indian Health Service data from 1999-2009, American Indian/Alaskan Native (AI/AN) women had approximately a two-fold higher incidence of cervical cancer and associated mortality rate than white women. This cervical cancer disparity is primarily attributed to a lack of screening and unequal access to healthcare; however, other factors such as a higher prevalence of high-risk Human Papillomavirus (hrHPV) in AI/AN women are likely contributors as well. Certain compositions of the vaginal microbiota (VMB), the microorganisms that colonize the vagina, have recently been implicated in the development of cervical cancer, and have been observed to differ between white women and Hispanic women, where cervical cancer rate disparities have also been reported. The goal of this proposal is to address the role of the VMB and inflammation in cervical cancer pathogenesis in AI/AN women. The central hypothesis is that the VMB functions as a key regulator of mucosal inflammation in the female reproductive tract (FRT) that could affect the development of precancerous lesions and progression to invasive disease. To test this hypothesis two specific aims will be addressed in a small pilot project involving 100 AI/AN women and 100 non-AI/AN controls (50 healthy women and 50 women with cervical dysplasia in each group). It is anticipated that the results of this study will provide the framework and preliminary evidence to support a larger project. In Aim 1, a culturally sensitive vaginal sample collection protocol for AI/AN women will be developed and implemented in collaboration with the Native Americans for Community Action (NACA) clinic in Flagstaff, AZ. Subsequently, in Aim 2 correlations will be calculated among the vaginal microbiome composition, host immune activity, HPV genotypes, and Lactobacillus abundances in AI/AN women and non-AI/AN women to better understand the relationship between these factors and cervical dysplasia and to explore for the first time whether differences exist in the VMB of AI/AN and non-AI/AN women. Impact: This study will also provide the context for training AI/AN students at Northern Arizona University, University of Arizona, and Arizona State University in cutting edge biomedical research, and will be a step toward bringing genomics-based health advances to AI/AN communities.