||5R01CA267842-02 Interpret this number
||Delineating the Underlying Reasons for the Racial Disparity in Gastric Cancer Incidence in the United States
The burden of gastric cancer falls disproportionately on racial/ethnic minorities in the US, with incidence rates among
Blacks, Asians, and Hispanics two- to three-fold higher than that among non-Hispanic whites. Further, individuals who self-
identify as belonging to any of these three groups are also more likely to die from gastric cancer, and comparing Black
men to White men, specifically, this mortality disparity is greater than that for all other cancers. In the US, gastric cancer
has a particularly low survival rate (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. Moreover, the racial disparity in gastric cancer continues to grow over time. And yet, the underlying reasons for
this racial disparity in gastric cancer incidence in the US are substantially understudied. The predominant cause of gastric
cancer is infection with the common bacterium, Helicobacter pylori (H. pylori). H. pylori is more prevalent among people
of color than non-Hispanic whites, and, in fact, H. pylori 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%). 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. These
potential other risk factors include key individual and neighborhood characteristics that differ greatly by race, 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 a diverse population in the US (67% non-white) 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 differences in race by 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 social
determinants of health on the patterns of H. pylori antibody levels, gastric atrophy and resulting disparities in gastric
cancer. 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.
Controlling Gastric Cancer in a World of Heterogeneous Risk.
, Laszkowska M.
, In H.
, Hwang J.H.
, Epplein M.
Gastroenterology, 2023 Apr; 164(5), p. 736-751.