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

项目总结/摘要：项目1 从美国人的透镜看美国本土宫颈癌的差异 阴道微生物组 在美国，每年诊断出约12，900例宫颈癌病例，年死亡率 超过四千人根据1999年至2009年的印度卫生服务数据，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 而不是白色女人。宫颈癌的这种差异主要是由于缺乏筛查和不平等的 获得医疗保健;然而，其他因素，如高风险人乳头瘤病毒的患病率较高 （hrHPV）在AI/AN妇女也可能是贡献者。阴道微生物群（VMB）的某些组成， 在阴道中定植的微生物，最近被认为与宫颈癌的发展有关。 癌症，并已观察到不同的白色妇女和西班牙裔妇女，其中宫颈癌 还报告了费率差异。本提案的目标是解决VMB的作用， 炎症在AI/AN妇女宫颈癌发病机制中作用核心假设是VMB 作为女性生殖道（FRT）粘膜炎症的关键调节因子， 癌前病变的发展和向侵袭性疾病的进展。为了验证这一假设， 具体目标将在一个小型试点项目中解决，该项目涉及100名人工授精/人工流产妇女和100名非人工授精/人工流产对照 (50健康妇女和宫颈发育不良妇女各50例。预计， 这项研究将提供框架和初步证据，以支持一个更大的项目。在目标1中， 将制定并实施针对AI/AN妇女的敏感阴道样本采集方案， 与亚利桑那州弗拉格斯塔夫的美国原住民社区行动诊所合作。随后在 目的2将计算阴道微生物组组成、宿主免疫活性、HPV之间的相关性 基因型和乳酸杆菌丰度在AI/AN妇女和非AI/AN妇女，以更好地了解 并首次探讨这些因素与宫颈不典型增生的关系是否存在差异 存在于AI/AN和非AI/AN女性的VMB中。影响：本研究还将提供培训背景 北方亚利桑那大学、亚利桑那大学和亚利桑那州立大学的AI/AN学生在切割 边缘生物医学研究，并将成为将基于基因组学的健康进步带入AI/AN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.