Unique Genomic Alterations and Microbial Profiles Identified in Patients With Gastric Cancer of African, European, and Asian Ancestry

Abstract

Objective: Here, we characterize differences in the genetic and microbial profiles of GC in patients of African (AFR), European, and Asian ancestry. Background: Gastric cancer (GC) is a heterogeneous disease with clinicopathologic variations due to a complex interplay of environmental and biological factors, which may affect disparities in oncologic outcomes.. Methods: We identified 1042 patients with GC with next-generation sequencing data from an institutional Integrated Mutation Profiling of Actionable Cancer Targets assay and the Cancer Genomic Atlas group. Genetic ancestry was inferred from markers captured by the Integrated Mutation Profiling of Actionable Cancer Targets and the Cancer Genomic Atlas whole exome sequencing panels. Tumor microbial profiles were inferred from sequencing data using a validated microbiome bioinformatics pipeline. Genomic alterations and microbial profiles were compared among patients with GC of different ancestries. Results: We assessed 8023 genomic alterations. The most frequently altered genes were TP53, ARID1A, KRAS, ERBB2, and CDH1. Patients of AFR ancestry had a significantly higher rate of CCNE1 alterations and a lower rate of KRAS alterations (P < 0.05), and patients of East Asian ancestry had a significantly lower rate of PI3K pathway alterations (P < 0.05) compared with other ancestries. Microbial diversity and enrichment did not differ significantly across ancestry groups (P > 0.05). Conclusions: Distinct patterns of genomic alterations and variations in microbial profiles were identified in patients with GC of AFR, European, and Asian ancestry. Our findings of variation in the prevalence of clinically actionable tumor alterations among ancestry groups suggest that precision medicine can mitigate oncologic disparities.