PROJECT ABSTRACT Gastric cancer is the fifth most common cancer worldwide, accounting for 780,000 deaths annually. In the US, a substantial burden of gastric cancer continues to be observed in American Indians (AI) in the Southwest and Alaska Natives. The Navajo Nation, a tribe in the Southwest, is experiencing higher incidence of gastric cancer compared to the general population in the region, possibly due to high prevalence of Helicobacter pylori (H. pylori) infection and other contributing factors, like diet. H. pylori strains that vary in the production of virulence factors have been credited with the causal link between H. pylori and gastric cancer. In particular, cytotoxin- associated gene A (cagA) and its pathogenicity island function together to deliver CagA proteins into host cells to promote inflammation and gastric cancer. Diets high in salt and processed meats, and low in fruits and vegetables were further associated with altering the protective lining of the stomach and enhancing expression of cagA. Thus, it is essential to understand the role of H. pylori and diet for gastric cancer prevention. While various treatment options for H. pylori infection are available, they are not always successful due to patient adherence and clinic level barriers, further leading to persistent infection and added expense. However, treatment failures in the Navajo Nation are unknown. My approach allows me to leverage my previous experience working with AI tribes to determine risk factors for gastric cancer and identify strategies to reduce them. I will implement my research among adults using the Navajo healthcare system. My objectives are two- fold. First, in the predoctoral F99 phase, I will determine the prevalence, virulence, and dietary correlates of H. pylori infection among Navajo adults. Second, in the postdoctoral K00 phase, I will characterize risk factors for H. pylori reinfection and patient experiences with H. pylori treatment. To achieve these objectives, I will use my previous experience in conducting health assessments to execute a cross-sectional study to measure H. pylori infection, cagA virulence gene status, and diet through health and diet surveys and laboratory analysis of stool specimens (F99). Then, I will use my gained expertise in H. pylori and previous experience with qualitative research to determine H. pylori reinfection risk and barriers to treatment adherence using quantitative and qualitative research approaches (K00). I will test my hypotheses through the following aims: AIM 1: Test that H. pylori infections, particularly with the cagA gene, are highly prevalent in Navajo adults compared to other non-AI populations, and that diets high in salt, processed meats, and low in vegetables are associated with H. pylori infection risk. AIM 2: Test that patient chronic health conditions are associated with H. pylori reinfection risk, and obtain information about patient-level and institutional level barriers to treatment adheren...