Project 3: Helicobacter pylori and stomach cancer among Native American populations

项目 3：美国原住民中的幽门螺杆菌和胃癌

• 批准号: 10021584
• 负责人: FERNANDO P MONROY
• 金额: $ 15.95万
• 依托单位: NORTHERN ARIZONA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021584
• 关键词: Arizona; Atrophic; Atrophic Gastritis; Authorization documentation; Behavioral; Biological Markers; Biopsy; Biopsy Specimen; Breath Tests; Cancer Burden; Cancer Etiology; Caring; Cells; Clinic; Clinical; Clinical Research; Communities; Development; Diagnosis; Diagnostic; Dietary History; Disease; Duodenal Ulcer; Endoscopy; Epithelial; Epithelium; Family; Gastric Metaplasia; Gastric Parietal Cells; Gastric Tissue; Gastric ulcer; Genotype; Goals; Health Services Accessibility; Helicobacter; Helicobacter Infections; Helicobacter pylori; Histologic; Histology; Homeostasis; Household; Human; Immune; Immune response; Improve Access; In Situ Hybridization; Incidence; Individual; Infection; Inflammatory; Interferons; Intestinal Metaplasia; Knowledge; Life Style; Ligands; Link; Malignant Neoplasms; Medical History; Mesenchymal; Metaplasia; Methods; MicroRNAs; Mucous Membrane; Mus; Myeloid-derived suppressor cells; Native Americans; Navajo; Outcome; Outpatients; Participant; Persons; Pilot Projects; Play; Population; Prevalence; Prevention strategy; Primary Prevention; Questionnaires; Research; Research Personnel; Risk; Risk Factors; Role; SHH gene; Sampling; Screening procedure; Secondary Prevention; Serum; Source; Stomach; Students; Surveys; Testing; Time; Underserved Population; United States; United States Indian Health Service; Urea; Virulence Factors; Water; Work; base; behavioral study; cancer prevention; care seeking; clinical care; cohort; education research; follow-up; genome analysis; health disparity; improved; malignant stomach neoplasm; member; mortality; mucosa-associated lymphoid tissue lymphoma; neoplastic; northern Native American; novel; pathogen; population based; recruit; screening; smoothened signaling pathway; social; socioeconomics; spasmolytic polypeptide; urban Native American; whole genome

PROJECT SUMMARY/ABSTRACT: PROJECT 3 HELICOBACTER PYLORI AND STOMACH CANCER AMONG NATIVE AMERICAN POPULATIONS Helicobacter pylori (Hp) is a common gastric pathogen that is associated with the development of duodenal or stomach ulcers, stomach cancer, and mucosa associated lymphoid-tissue (MALT) lymphomas. While the overall incidence of gastric cancer has declined over time in the United States (US), there are clear racial and socioeconomic health disparities in gastric cancer rates and associated outcomes. This translational, multi- method project seeks to better understand the role of Hp infection in the development of stomach cancer among Native Americans (NA) of Northern Arizona where stomach cancer incidence rates are approximately three times as high compared to the general Arizona population and it is the leading cause of cancer-related mortality. Despite this high burden, social, environmental, and pathogen-associated risk factors remain unknown for this underserved population. While prevalence varies within populations, Hp prevalence within Navajo Nation is likely high. Our pilot study of 72 households found 59% of 108 participants were Hp positive by urea breath test (UBT) and 74% of households had at least one person positive. Furthermore, prior knowledge of Hp and its link to stomach cancer is low in these communities. However, 53% of Hp+ cases did seek care at the local urban Indian Health Service facility, indicating concern. Risk factors for Hp infection in this distinct population are not clearly defined nor are barriers to receiving diagnosis and treatment, precluding appropriate primary and secondary prevention strategies. Thus Aim 1 is a community-based study to identify factors associated with infection and barriers to self-referral to clinic. Since Hp subtypes may contribute to progression from infection to cancer and the prevalence of specific genotypes are unknown in this population, Aim 2 will focus on the distribution of Hp subtypes in the Navajo community members referred to clinic for endoscopy. The relationship between Hp infection and subsequent stomach cancer is related also to host immune response. Intestinal metaplasia and Spasmolytic Polypeptide-expressing metaplasia (SPEM) are histologic changes that presage gastric cancer development. SPEM is more intensively studied in mice than humans because it can be induced experimentally after introducing Helicobacter. Epithelial expression of the sonic hedgehog (Shh) ligand and mesenchymal activation of canonical Hedgehog signaling play essential roles in gastric homeostasis and recruitment of inflammatory cells. Our earlier studies found a subset of immune cells recruited to the gastric epithelium during infection become myeloid-derived suppressor cells (MDSCs), and this coincides with parietal cell atrophy and SPEM. Schlafens (SLFN) are a family of molecules strongly induced by type 1 interferons that correlate with immune cell quiescence. Using whole genome analysis of mouse cells, we identified a microRNA signature for this IFN-regulated immune cell in both metaplastic gastric tissue and serum of both infected mice and humans. Thus, in Aim 3 a miRNA signature will be analyzed in the gastric biopsies and compared to its presence in serum collected at time of endoscopy.

项目摘要/摘要：项目 3 美洲原住民中的幽门螺杆菌和胃癌 幽门螺杆菌 (Hp) 是一种常见的胃病原体，与十二指肠或十二指肠的发育有关。 胃溃疡、胃癌和粘膜相关淋巴组织 (MALT) 淋巴瘤。虽然整体 在美国，胃癌的发病率随着时间的推移呈下降趋势，存在明显的种族和 胃癌发病率和相关结果的社会经济健康差异。这种翻译性的、多 方法项目旨在更好地了解 Hp 感染在胃癌发展中的作用 在亚利桑那州北部的美洲原住民 (NA) 中，胃癌发病率约为 是亚利桑那州普通人口的三倍，是癌症相关的主要原因 死亡。尽管负担很重，但社会、环境和病原体相关的危险因素仍然未知 对于这个服务不足的人群。虽然人群中的患病率有所不同，但纳瓦霍族内的 Hp 患病率 可能很高。我们对 72 个家庭进行的试点研究发现，108 名参与者中有 59% 的尿素呼吸呈幽门螺杆菌阳性 测试（UBT），74％的家庭至少有一人呈阳性。此外，对 Hp 及其产品的先验知识 在这些社区中，与胃癌的关联性较低。然而，53% 的 Hp+ 病例确实到当地城市就医 印度卫生服务机构表示担忧。这一独特人群中 Hp 感染的危险因素是 没有明确定义，也没有接受诊断和治疗的障碍，排除了适当的初级治疗 和二级预防策略。因此，目标 1 是一项基于社区的研究，旨在确定相关因素 存在感染和自我转诊障碍。由于 Hp 亚型可能导致感染进展 癌症的发生率以及该人群中特定基因型的患病率未知，目标 2 将重点关注 纳瓦霍社区成员转诊至诊所进行内窥镜检查的 Hp 亚型分布。关系 Hp 感染与随后的胃癌之间也与宿主免疫反应有关。肠 化生和表达解痉多肽的化生 (SPEM) 是预示的组织学变化 胃癌的发展。 SPEM 在小鼠身上的研究比在人类身上进行的更深入，因为它可以被诱导 引入螺杆菌后进行实验。声波刺猬 (Shh) 配体的上皮表达 典型 Hedgehog 信号的间充质激活在胃稳态和 炎症细胞的募集。我们早期的研究发现，一部分免疫细胞被招募到胃中 感染期间上皮细胞变成骨髓源性抑制细胞（MDSC），这与壁层细胞一致 细胞萎缩和SPEM。 Schlafens (SLFN) 是由 1 型干扰素强烈诱导的分子家族， 与免疫细胞静止相关。通过对小鼠细胞的全基因组分析，我们鉴定出了一种 microRNA 两只受感染小鼠化生胃组织和血清中这种 IFN 调节的免疫细胞的特征 和人类。因此，在目标 3 中，将对胃活检中的 miRNA 特征进行分析，并与其比较 在内窥镜检查时收集的血清中存在。