AS696 - Delineating the underlying reasons for the racial disparity in gastric cancer incidence in the United States
Investigator Names and Contact Information
Meira Epplein (meira.epplein@duke.edu)
Introduction/Intent
The burden of gastric cancer falls disproportionately on racial/ethnic minorities in the US, with incidence rates among Blacks, Asian Americans, and Hispanics two- to three-fold higher than that among non-Hispanic whites. Significantly, individuals from all of these groups are also more likely to die from gastric cancer, and comparing Blacks to whites, specifically, this mortality disparity is the highest compared to all other cancers. The underlying reasons for this racial disparity are significantly understudied. The predominant cause of gastric cancer is infection with the common bacteria, Helicobacter pylori (H. pylori). H. pylori is more prevalent among non-Whites and Hispanics than non-Hispanic Whites (approximately 50% vs. 30% in the US, respectively). Currently, however, little is known about whether the disparity in gastric cancer is 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. There have been numerous laboratory studies showing that Blacks are more likely to harbor H. pylori strains carrying the cagA gene (a gastric-cancer associated virulence factor) than Whites. Our own data demonstrate that increased host antibody response to H. pylori virulence factors, including CagA, are correlated with increased risk of gastric precancerous lesions, and moreover the host antibody response is found at significantly higher levels among H. pylori-positive Blacks and Asians than H. pylori-positive Whites. However, no one has yet examined the full scope of risk factors, including host response to H. pylori infection along with other factors associated with immune response, including smoking status, diet, and body mass index, in the US and how these might contribute to observed racial disparities. We will also examine individual and neighborhood factors, such as household crowding, socio-economic status (SES), and residential segregation, that lead to stress for the host and could contribute to a more severe immune response to H. pylori, and may be differential by race, that could then drive gastric cancer development. In our previous R01, we identified antibodies to specific H. pylori proteins as non-invasive biomarkers for gastric cancer risk in East Asia. Here, we propose to build on this novel finding to explore how these markers, along with other factors, may explain for the racial disparity in gastric cancer incidence in the US. Our goal is to fill the gap in knowledge of risk factors for H. pylori-associated gastric cancer to ultimately inform risk stratification for the US population. To do this, we will build a nested case-control study of 796 non-cardia gastric cancer cases and 2:1 matched controls, utilizing prospective cohort data from a diverse population in the US (66% non-white) from 4 NCI-funded cohorts with pre-diagnostic specimens available (MEC, PLCO, SCCS, WHI).
The Specific Aims of this study are:
Aim 1: Examine the association of individual (smoking, BMI) and neighborhood (household crowding, SES, residential segregation) factors with gastric cancer risk in a diverse population in the US.
Aim 2: Assess what drives the difference by race in H. pylori antibody levels and atrophy and resulting gastric cancer risk.
Aim 3: Develop an integrated “cells to society” modeling framework to assess the impact of social determinants of health on the patterns of H. pylori antibody levels, gastric atrophy and resulting disparities in gastric cancer risk.
