Helicobacter Infection and Liver Cancer Risk among African Americans and Whites in the United States

美国非裔美国人和白人中的螺杆菌感染和肝癌风险

基本信息

批准号：
10275917
负责人：
Xuehong Zhang
金额：
$ 45.49万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-16 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10275917
关键词：
Affect African American Animal Experiments Animals Antibody Response Bacteria Bacterial Infections Biological Assay Blood specimen Cancer Etiology Carcinoma Case Management Cessation of life Clinical Cytotoxin DNA Damage Data Diabetes Mellitus Diagnostic Ethnic Origin Ethnic group Etiology Goals Grant Growth Helicobacter Helicobacter Infections Helicobacter hepaticus Helicobacter pylori Hepatitis B Hepatitis B Virus Hepatitis C Hepatitis C virus Hepatocarcinogenesis Hepatocyte High Prevalence Human Incidence Infection Intervention Investigation Liver Malignant neoplasm of liver Measures Metabolic Diseases Mouse Strains Nested Case-Control Study Not Hispanic or Latino Obesity Odds Ratio Pathogenicity Island Population Prevalence Prevention Prospective Studies Prospective cohort study Proteins Race Research Resources Risk Risk Factors Role Tissues United States Vacuole Viral Virulence Factors Virus Woman Work angiogenesis base cancer health disparity cancer risk carcinogenicity case control chronic infection co-infection cohort design epidemiology study ethnic diversity ethnic minority population infection risk innovation men mortality novel novel strategies prevent racial and ethnic racial diversity seropositive therapy design viral carcinogenesis

项目摘要

Project Summary Liver cancer in the U.S. has tripled since the 1980s and is now among the leading causes of cancer deaths. Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are common causes of liver cancer, ~70% of liver cancer is non-viral in the U.S., though we know little about its risk factors. The essential role of Helicobacter pylori (H. pylori), and other Helicobacter species in liver carcinogenesis (i.e., H. bilis, H. hepaticus) has recently been described in animal studies. These species also colonize in human liver tissue, but very limited research has assessed H. pylori or other Helicobacter species and liver cancer. We propose a pooled prospective study using the cohorts participating in the Liver Cancer Pooling Project in the U.S. that will be the most comprehensive study to date of H. pylori, other Helicobacter species, and liver cancer. Our long- term goal is to identify novel risk factors for liver cancer of both viral and non-viral etiology. Furthermore, although liver cancer disproportionally affects racial/ethnic minorities, the underlying causes remain unclear. Our pilot work showed that African Americans (AAs) have higher prevalence than whites in overall H. pylori infection (89% vs. 60%), CagA-positive (75% vs. 36%), and VacA-positive infection (94% vs. 88%), suggesting a novel approach to determine the extent to which high prevalence of Helicobacter infection could explain liver cancer disparity. The objective of this grant is to (1) identify H. pylori and other Helicobacter infection as novel risk factors for liver cancer, especially those with non-viral etiology; and (2) investigate the differences in prevalence of Helicobacter infection by racial/ethnic groups that could explain liver cancer disparity. Our rationale is that identification of the key bacteria as risk factors for liver cancer will offer new opportunities for prevention and intervention of liver cancer and reducing related disparities. Our specific aims will estimate the associations between H. pylori infection and risk of developing liver cancer overall and by viral status (Aim 1); quantify the associations between other Helicobacter infection and risk of developing liver cancer overall and by viral status (Aim 2); and characterize the associations between Helicobacter infection and risk of liver cancer separately for AAs and whites (Aim 3). This will enable us to identify the role of H. pylori and other Helicobacter species in liver carcinogenesis by viral status and race/ethnicity. This research is innovative because we are the first pooled study to use a unique resource of >408,700 racially and ethnically diverse men and women who have been followed for up to 32 years, distinguish between viral and non-viral liver cancer, and quantify the association between H. bills and H. hepaticus infection and liver cancer risk in AAs and whites. The contribution is significant because these discoveries will facilitate design of innovative intervention strategies to reduce liver cancer incidence, mortality, and related disparities in populations.

项目概要自 20 世纪 80 年代以来，美国的肝癌发病率增加了两倍，目前已成为癌症死亡的主要原因之一。虽然乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染是肝癌的常见原因，在美国，约 70% 的肝癌是非病毒性的，尽管我们对其危险因素知之甚少。的重要作用幽门螺杆菌 (H. pylori) 和肝癌发生过程中的其他螺杆菌 (即 H. bilis、H. hepacus）最近在动物研究中得到了描述。这些物种也在人类肝脏组织中定居，但评估幽门螺杆菌或其他螺杆菌与肝癌之间关系的研究非常有限。我们提出一个使用参与美国肝癌汇集项目的队列进行的汇总前瞻性研究这是迄今为止关于幽门螺杆菌、其他螺杆菌和肝癌的最全面的研究。我们的长期长期目标是确定病毒性和非病毒性肝癌的新危险因素。此外，尽管肝癌对少数种族/族裔的影响不成比例，但其根本原因仍不清楚。我们的试点工作表明，非裔美国人 (AA) 的幽门螺杆菌总体患病率高于白人感染（89% vs. 60%）、CagA 阳性（75% vs. 36%）和 VacA 阳性感染（94% vs. 88%），表明一种确定螺杆菌感染高流行程度可以解释肝脏疾病的新方法癌症差异。这笔赠款的目的是 (1) 将幽门螺杆菌和其他螺杆菌感染确定为新型感染肝癌的危险因素，特别是那些非病毒性病因的因素； (2) 调查差异种族/民族群体中螺杆菌感染的患病率可以解释肝癌的差异。我们的其基本原理是，确定肝癌危险因素的关键细菌将为研究提供新的机会。预防和干预肝癌并减少相关差异。我们的具体目标将估计幽门螺杆菌感染与整体肝癌风险和病毒状态之间的关联（目标 1）；量化其他螺杆菌感染与罹患肝癌风险之间的总体关联，以及按病毒状态分类（目标 2）；并描述螺杆菌感染与肝病风险之间的关系分别针对 AA 和白人癌症（目标 3）。这将使我们能够确定幽门螺杆菌和其他细菌的作用按病毒状态和种族/民族划分的肝癌发生中的螺杆菌种类。这项研究具有创新性因为我们是第一个使用超过 408,700 名不同种族和民族男性的独特资源的汇总研究以及被跟踪长达 32 年的女性，区分病毒性肝癌和非病毒性肝癌，并量化 AA 和 H. bills 和 H. hepaticus 感染与肝癌风险之间的关联白人。这一贡献意义重大，因为这些发现将促进创新干预措施的设计降低肝癌发病率、死亡率和相关人群差异的策略。