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.
| Gilbert, Jack A; Blaser, Martin J; Caporaso, J Gregory et al. (2018) Current understanding of the human microbiome. Nat Med 24:392-400 |
| Bokulich, Nicholas A; Dillon, Matthew R; Zhang, Yilong et al. (2018) q2-longitudinal: Longitudinal and Paired-Sample Analyses of Microbiome Data. mSystems 3: |
| Varadaraj, Archana; Magdaleno, Carina; Mythreye, Karthikeyan (2018) Deoxycholate Fractionation of Fibronectin (FN) and Biotinylation Assay to Measure Recycled FN Fibrils in Epithelial Cells. Bio Protoc 8: |
| Bea, Jennifer W; de Heer, Hendrik Dirk; Valdez, Luis et al. (2018) Physical Activity among Navajo Cancer Survivors: A Qualitative Study. Am Indian Alsk Native Ment Health Res 25:54-73 |
| Bokulich, Nicholas A; Kaehler, Benjamin D; Rideout, Jai Ram et al. (2018) Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2's q2-feature-classifier plugin. Microbiome 6:90 |
| Huenneke, Laura F; Stearns, Diane M; Martinez, Jesse D et al. (2017) Key Strategies for Building Research Capacity of University Faculty Members. Innov High Educ 42:421-435 |
| Jim, Venessa; LaViolette, Corinne; Briehl, Margaret M et al. (2017) Spatial distribution of uranium in mice kidneys detected by laser ablation inductively coupled plasma mass spectrometry. J Appl Bioanal 3:43-48 |
| Schwartz, Anna L; de Heer, Hendrik Dirk; Bea, Jennifer W (2017) Initiating Exercise Interventions to Promote Wellness in Cancer Patients and Survivors. Oncology (Williston Park) 31:711-7 |
| Bokulich, Nicholas A; Rideout, Jai Ram; Mercurio, William G et al. (2016) mockrobiota: a Public Resource for Microbiome Bioinformatics Benchmarking. mSystems 1: |
| Corlin, Laura; Rock, Tommy; Cordova, Jamie et al. (2016) Health Effects and Environmental Justice Concerns of Exposure to Uranium in Drinking Water. Curr Environ Health Rep 3:434-442 |
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