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，每年导致78万人死亡。在美国， 在美国西南部的印第安人(AI)中，胃癌的负担仍然很大 阿拉斯加原住民。西南部的一个部落纳瓦霍民族正经历着更高的胃癌发病率 与该区域普通人群相比，这可能是由于幽门螺杆菌(H. 幽门螺杆菌)感染和其他致病因素，如饮食。产生不同毒力的幽门螺杆菌菌株 幽门螺杆菌与胃癌之间的因果联系已被认为是多种因素造成的。尤其是细胞毒素- 相关基因A(CagA)及其致病岛共同作用将CagA蛋白送入宿主细胞 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衬里和增强表情有关 CagA的。因此，了解幽门螺杆菌和饮食在预防胃癌中的作用是至关重要的。而当 幽门螺杆菌感染有多种治疗方案，但由于患者的原因，它们并不总是有效的 依从性和临床水平障碍，进一步导致持续感染和增加费用。然而， 纳瓦霍民族的治疗失败是未知的。我的方法使我能够利用我以前的 与人工智能部落合作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。我的目标有两个- 收牌。首先，在博士前F99阶段，我将确定流行率、毒性和饮食相关因素 在纳瓦霍成年人中感染幽门螺杆菌的情况。第二，在博士后K00阶段，我将描述风险 幽门螺杆菌再感染的因素和患者接受幽门螺杆菌治疗的经验。要实现这些目标 目标，我将利用我以前进行健康评估的经验来执行横断面 通过健康和饮食调查测量幽门螺杆菌感染、cagA毒力基因状态和饮食的研究 粪便样本的实验室分析(F99)。然后，我将使用我在幽门螺杆菌和以前的专业知识 确定幽门螺杆菌再感染风险和治疗依从性障碍的定性研究经验 使用定量和定性研究方法(K00)。我将通过以下几点来检验我的假设 目标：目标1：检测幽门螺杆菌感染，特别是cagA基因感染在纳瓦霍成年人中高度流行 与其他非人工智能人群相比，高盐饮食、加工肉类和低蔬菜饮食是 与幽门螺杆菌感染风险相关。目的2：检验患者慢性健康状况与H. 幽门螺杆菌再感染风险，并获得有关患者层面和机构层面治疗障碍的信息 坚持不懈。我提议的研究将阐明人们对胃癌危险因素的理解 纳瓦霍，一个经历着高疾病负担的人口，目标是制定干预措施以改善 癌症结果，与美国国家癌症研究所和美国国立卫生研究院的使命一致。

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.