ERBB2 amplification in gastric cancer: a genomic insight into ethnic disparities

Abstract

Overall, gastric adenocarcinoma (GC) incidence rates have declined in recent years, but racial and ethnic disparities persist. Individuals who identify as Hispanic/Spanish/Latino are diagnosed with GC at younger ages and have poorer outcomes than non-Hispanic individuals. However, our understanding of GC biology across racial/ethnic groups remains limited. We assessed tumor genomic patterns by race/ethnicity among 1019 patients with primary GC in the American Association for Cancer Research (AACR) Project GENIE Consortium. Hispanic individuals presented with significantly higher rates of ERBB2/HER2 amplification vs other racial/ethnic groups (Hispanic: 13.9% vs 9.8% non-Hispanic White, 8.1% non-Hispanic Asian, and 11.0% non-Hispanic Black; P < .001, FDR adjusted q < 0.001). Hispanic patients also had higher odds of an ERBB2 amplification vs non-Hispanic Whites in adjusted models (OR = 2.52, 95%CI = 1.20 to 5.33, P = .015). These findings underscore the important role of genomic factors in GC disparities. Ensuring equitable access to genomic profiling and targeted therapies, such as trastuzumab for HER2-overexpressing GC, is a promising avenue to mitigate GC disparities and improve outcomes.

Figure 1.

Gastric adenocarcinoma mutation patterns by self-identified race and ethnicity: AACR Project GENIE. A) Composition of the study population with inclusion criteria. B) Distribution of self-identified races and ethnicities within the cohort. C) Prevalence and spectrum of somatic alterations across racial/ethnic groups. ERBB2 and CCNE1 are restricted to gene amplification. *P value < .05, and q-value < 0.10. V = version; N = number; AMP = amplification; Δ = non-silent mutation.