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: 10672894
• 负责人: Xuehong Zhang
• 金额: $ 39.17万
• 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/10672894
• 关键词: Affect; African American population; 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; Disparity; Ethnic Origin; Ethnic Population; Etiology; Goals; Grant; Growth; Helicobacter; Helicobacter Infections; Helicobacter hepaticus; Helicobacter pylori; Hepatitis B Infection; Hepatitis B Virus; Hepatitis C; Hepatitis C virus; Hepatocarcinogenesis; Hepatocyte; High Prevalence; Human; Incidence; Infection; Intervention; Invaded; 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; Predisposition; Prevalence; Prevention; Prospective Studies; Prospective, cohort study; Proteins; Race; Research; Resources; Risk; Risk Factors; Role; Tissues; United States; Viral; Virulence Factors; Virus Diseases; Woman; Work; angiogenesis; cancer health disparity; cancer risk; carcinogenicity; chronic infection; co-infection; cohort; design; epidemiology study; ethnic diversity; ethnic minority; innovation; men; mortality; novel; novel strategies; prevent; racial diversity; racial minority; racial population; 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20世纪80年代以来，美国的肝癌增加了两倍，现在是癌症死亡的主要原因之一。 虽然B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.幽门螺杆菌），以及肝癌发生中的其它螺杆菌种类（即，H. bilis，H. hepaticus）最近在动物研究中被描述。这些物种也在人类肝脏组织中定居， 但对H.幽门螺杆菌或其他螺杆菌物种和肝癌。我们提出了一个 使用参与美国肝癌汇总项目的队列进行的汇总前瞻性研究， 是迄今为止对H.幽门螺杆菌、其他螺杆菌和肝癌。我们长久以来- 长期目标是确定病毒和非病毒病因学肝癌的新危险因素。此外，委员会认为， 尽管肝癌对少数种族/民族的影响尤其严重，但其根本原因仍不清楚。 我们的试点工作表明，非洲裔美国人（AAs）在总体H。幽门 感染（89%对60%），CagA阳性（75%对36%）和VacA阳性感染（94%对88%），表明 一种新的方法来确定螺杆菌感染的高患病率在多大程度上可以解释肝脏 癌症差异本基金的目的是（1）鉴定H.幽门螺杆菌和其他幽门螺杆菌感染作为新的 肝癌的危险因素，特别是那些非病毒病因;和（2）调查 可以解释肝癌差异的种族/民族组的螺杆菌感染患病率。我们 基本原理是，确定关键细菌作为肝癌的危险因素将为肝癌的治疗提供新的机会。 预防和干预肝癌，减少相关差距。我们的具体目标将估计 H之间的联系。幽门螺杆菌感染和发展为肝癌的风险的整体和病毒状态（目标1）; 量化其他螺杆菌感染与整体肝癌风险之间的关联， 通过病毒状态（目的2）;并描述螺杆菌感染和肝脏风险之间的关系 癌症分别为AA和白人（目标3）。这将使我们能够确定H的作用。幽门螺杆菌和其他 根据病毒状态和人种/种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名种族和民族多样化男性的独特资源的汇总研究 以及随访长达32年的女性，区分病毒性和非病毒性肝癌， 并量化了H. bills和H.肝细胞感染和肝癌风险， 白人这一贡献是重要的，因为这些发现将促进创新干预的设计 降低肝癌发病率、死亡率和相关人群差异的策略。

项目成果

Higher ultra-processed food intake was positively associated with odds of NAFLD in both US adolescents and adults: A national survey.

• DOI: 10.1097/hc9.0000000000000240
• 发表时间: 2023-09-01
• 期刊: Hepatology communications
• 影响因子: 5.1

Dietary inflammatory and insulinemic potential, risk of hepatocellular carcinoma, and chronic liver disease mortality.

• DOI: 10.1093/jncics/pkad023
• 发表时间: 2023-03-01
• 期刊: JNCI cancer spectrum
• 影响因子: 4.4

Specific botanical groups of fruit and vegetable consumption and liver cancer and chronic liver disease mortality: a prospective cohort study.

• DOI: 10.1016/j.ajcnut.2022.12.004
• 发表时间: 2022-12
• 期刊: The American journal of clinical nutrition
• 作者: Longgang Zhao;Lina Jin;J. Petrick;Hongmei Zeng;Fenglei Wang;Li Tang;S. Smith-Warner;A. Eliassen;F. Zhang;P. Campbell;E. Giovannucci;L. Liao;K. McGlynn;S. Steck;Xuehong Zhang

Association of dietary insulinemic and inflammatory potential with risk of liver cancer and chronic liver disease mortality in postmenopausal women: a prospective cohort study.

绝经后妇女膳食胰岛素和炎症潜力与肝癌和慢性肝病死亡率的关联：一项前瞻性队列研究。

• DOI: 10.1016/j.ajcnut.2023.07.009
• 发表时间: 2023
• 期刊: The American journal of clinical nutrition
• 作者: Zhang,Xinyuan;Zhao,Longgang;Christopher,CamiN;Tabung,FredK;Bao,Wei;Garcia,DavidO;Shadyab,AladdinH;Saquib,Nazmus;Neuhouser,MarianL;Tinker,LesleyF;Zhang,Xuehong
• 通讯作者: Zhang,Xuehong