Grant Number:	7R37CA262299-04 Interpret this number
Primary Investigator:	Zhang, Xuehong
Organization:	Yale University
Project Title:	Helicobacter Infection and Liver Cancer Risk Among African Americans Andwhites in the United States
Fiscal Year:	2024

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.





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