Grant Number:	5R01CA267842-04 Interpret this number
Primary Investigator:	Epplein, Meira
Organization:	Duke University
Project Title:	Delineating the Underlying Reasons for the Racial Disparity in Gastric Cancer Incidence in the United States
Fiscal Year:	2025

In the United States, gastric cancer is a particularly fatal disease (survival rate of approximately 32% at 5 years) as it is generally asymptomatic until late-stage, when treatment is no longer effective. Each year in the US, 26,000 people are diagnosed with gastric cancer, and over 10,000 people die of the disease. However, gastric cancer is a preventable disease, as the predominant cause of gastric cancer is infection with the common bacterium, Helicobacter pylori (H. pylori), for which successful eradication significantly reduces the risk of developing gastric cancer. H. pylori, which greatly varies in prevalence among different populations within the US, is the world’s single leading carcinogenic infectious agent, responsible for an estimated 36.9% of the over 2.2 million infection-associated cancers diagnosed in 2018, more even than those attributed to human papillomavirus (31.5%), or the Hepatitis B and C viruses combined (23.5%). The burden of gastric cancer also falls disproportionately on different populations within the US, with incidence rates two- to three-fold higher in different groups of individuals, which is also mirrored in gastric cancer mortality rates. Moreover, these differences in gastric cancer incidence continue to grow over time. And yet, the underlying reasons for these population-based differences in gastric cancer incidence in the US are substantially understudied. Currently, little is known about whether the differences in gastric cancer incidence are a result of differences in H. pylori prevalence, host response to H. pylori, or differences in other risk factors that might affect the development of gastric cancer. These potential other risk factors include key individual and neighborhood characteristics that differ greatly within populations, such as household crowding and residential segregation, which could increase the risk of H. pylori infection, contribute to chronic stress, and induce a more severe immune response. Our goal is to fill the gap in knowledge of risk factors for H. pylori-associated gastric cancer to provide the understanding of the underlying factors that indicate who is at high risk of gastric cancer in the US. To do this, we will build a nested case-control study of approximately 800 non-cardia gastric cancer cases and 2:1 matched controls, utilizing prospective cohort data from 4 NCI-funded cohorts with pre-diagnostic specimens available: Multiethnic Cohort Study (MEC); Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO); Southern Community Cohort Study (SCCS); and Women’s Health Initiative (WHI). We will assay these biospecimens for antibody levels to H. pylori-specific proteins and for pepsinogen (a validated marker of gastric atrophy), thoroughly assess individual and neighborhood factors that are associated with gastric cancer risk, and determine what drives the population differences in H. pylori antibody levels and atrophy and resulting gastric cancer risk. Finally, we will develop an integrated “cells to society” modeling framework to assess the impact of multi-level determinants of health on the patterns of H. pylori antibody levels, gastric atrophy and resulting population differences in gastric cancer incidence. Ultimately, these findings will provide the information needed to allow for targeting of high-risk patients for the clinical trials necessary to create screening guidelines for the prevention and early detection of gastric cancer in the US, and will help clinicians with precision prevention by laying the groundwork for the building of a risk prediction tool.




Racial/ethnic differences in risk factors for non-cardia gastric cancer: an analysis of the Multiethnic Cohort (MEC) Study.
Authors: Adams A. , Gandhi A. , Friedmann P. , Sarkar S. , Rana B. , Epplein M. , Wilkens L. , Huang B.Z. , In H. .
Source: Cancer Causes & Control : Ccc, 2024-11-07 00:00:00.0; , .
EPub date: 2024-11-07 00:00:00.0.
PMID: 39509055
Related Citations

Reply to S. Sorscher.
Authors: Butt J. , Epplein M. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2024-09-10 00:00:00.0; 42(26), p. 3163-3164.
EPub date: 2024-06-27 00:00:00.0.
PMID: 38935899
Related Citations

Controlling Gastric Cancer in a World of Heterogeneous Risk.
Authors: Huang R.J. , Laszkowska M. , In H. , Hwang J.H. , Epplein M. .
Source: Gastroenterology, 2023-01-24 00:00:00.0; , .
EPub date: 2023-01-24 00:00:00.0.
PMID: 36706842
Related Citations