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

• 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
• 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; 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

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.

项目摘要 自1980年代以来，美国的肝癌已经增加了两倍，现在是癌症死亡的主要原因之一。 尽管丙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染是肝癌的常见原因，但 在美国，〜70％的肝癌是非病毒的，尽管我们对其危险因素知之甚少。的基本角色 幽门螺杆菌（H. Pylori）和其他螺旋细菌在肝癌发生中（即H. Bilis，H。 最近在动物研究中进行了描述。这些物种也在人肝组织中定植， 但是，研究非常有限的研究评估了幽门螺杆菌或其他螺旋杆菌和肝癌。我们提出了一个 使用参与美国肝癌集合项目的同类人群的汇总前瞻性研究 成为幽门螺杆菌，其他螺旋杆菌和肝癌迄今为止最全面的研究。我们的长期 术语目标是确定病毒和非病毒病因的肝癌的新风险因素。此外， 尽管肝癌不成比例地影响种族/族裔少数群体，但基本原因尚不清楚。 我们的飞行员工作表明，非洲裔美国人（AAS）的患病率高于幽门螺杆菌的白人 感染（89％比60％），CAGA阳性（75％vs. 36％）和VACA阳性感染（94％vs. 88％），这表明 一种新的方法来确定高螺旋杆菌感染的高流行率可以解释肝脏 癌症差异。这项赠款的目的是（1）将幽门螺杆菌和其他螺旋杆菌感染确定为新颖 肝癌的危险因素，尤其是患有非病毒病因的危险因素； （2）研究 种族/族裔群体感染的螺旋杆菌患病率可以解释肝癌差异。我们的 理由是，将关键细菌鉴定为肝癌的危险因素将为新的机会 肝癌的预防和干预以及减少相关差异。我们的具体目标将估计 幽门螺杆菌感染与整体肝癌的风险之间的关联（AIM 1）； 量化其他螺旋杆菌感染与整体肝癌的风险之间的关联 通过病毒状态（目标2）；并表征了旋转杆菌感染与肝脏风险之间的关联 分别用于AA和白人的癌症（AIM 3）。这将使我们能够确定幽门螺杆菌和其他幽门螺杆菌的作用 通过病毒状况和种族/种族，肝癌发生中的螺旋杆菌物种。这项研究是创新的 因为我们是首次使用> 408,700种种族和种族多样性的独特资源的合并研究 以及最多32年的妇女，区分病毒和非病毒肝癌， 并量化AAS和肝癌感染和肝癌风险的H. Bill和H. 白人。贡献很重要，因为这些发现将有助于设计创新干预 减少肝癌发病率，死亡率和相关差异的策略。