Assessing Helicobacter pylori and Diet to Develop Cancer Interventions in American Indian Communities in the Southwest

项目摘要 胃癌是全球第五大常见癌症，每年造成78万人死亡。在美国， 在西南部的美洲印第安人（AI）中继续观察到胃癌的大量负担， 阿拉斯加土著纳瓦霍族是美国西南部的一个部落， 与该地区的一般人群相比，可能是由于幽门螺杆菌（H. pylori）感染和其他影响因素，如饮食。H.在产生毒力方面不同的幽门螺杆菌菌株 因素与H.幽门螺杆菌和胃癌。尤其是细胞毒素- 相关基因A（cagA）与其致病岛共同作用，将CagA蛋白递送到宿主细胞中 促进炎症和胃癌。高盐和加工肉类的饮食，低水果和 蔬菜还与改变胃的保护膜和增强表达有关， 关于cagA因此，了解H的作用是至关重要的。幽门螺杆菌和饮食预防胃癌。而 各种治疗方案H.幽门螺杆菌感染是可用的，他们并不总是成功的，由于病人 依从性和诊所水平的障碍，进一步导致持续感染和增加的费用。然而，在这方面， 纳瓦霍族的治疗失败情况尚不清楚。我的方法可以让我利用我以前的 与AI部落合作的经验，以确定胃癌的风险因素，并确定减少 他们我将在使用纳瓦霍医疗保健系统的成年人中实施我的研究。我有两个目标- 折首先，在博士前的F99阶段，我将确定患病率、毒力和饮食相关性 阁下于纳瓦霍成年人中的幽门螺杆菌感染。第二，在博士后K 00阶段，我将描述风险 因子H. pylori再感染和患者感染H.幽门螺杆菌治疗实现这些 目标，我将利用我以前进行健康评估的经验， 研究测定H.幽门螺杆菌感染，cagA毒力基因状态和饮食，通过健康和饮食调查， 粪便标本的实验室分析（F99）。然后，我将利用我在H方面获得的专业知识。幽门螺杆菌及既往 定性研究的经验，以确定H。幽门螺杆菌再感染风险和治疗依从性障碍 使用定量和定性研究方法（K 00）。我将通过以下内容来检验我的假设 目的：目的1：测试H.幽门螺杆菌感染，特别是cagA基因，在纳瓦霍成年人中非常普遍 与其他非AI人群相比，高盐、加工肉类和低蔬菜的饮食 与H.幽门螺杆菌感染风险。目的2：检验慢性健康状况与H. 幽门螺杆菌再感染风险，并获得有关患者和机构层面的治疗障碍的信息 坚持。我提出的研究将阐明对胃癌危险因素的理解， 纳瓦霍人，一个经历高疾病负担的人口，目标是制定干预措施， 癌症结果，与NCI和NIH的使命一致。

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 adherence. My proposed research will elucidate an understanding of risk factors for gastric cancer among the Navajo, a population experiencing a high disease burden, with the goal of developing interventions to improve cancer outcomes, in alignment with the mission of the NCI and NIH.