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

Abstract

Introduction: Gastric cancer (GC) is a heterogenous disease with clinicopathologic variations due to a complex interplay of environmental and biological factors, which may affect disparities in oncologic outcomes. Here, we characterize differences in the genetic and microbial profiles of GC in patients of African, European, and Asian ancestry. Methods: We identified 1,042 GC patients with next-generation sequencing (NGS) data from an institutional Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) assay and the Cancer Genomic Atlas (TCGA) group. Genetic ancestry was inferred from markers captured by the IMPACT and TCGA 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 between GC patients of different ancestries. Results: We assessed 8,023 genomic alterations. The most frequently altered genes were TP53, ARID1A, KRAS, ERBB2, and CDH1. Patients of African 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 to other ancestries. Microbial diversity and enrichment did not differ significantly across ancestry groups (P>0.05). Discussion: Distinct patterns of genomic alterations and variations in microbial profiles were identified in GC patients of African, 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.

Unravelling diagnostic clusters and immune landscapes of disulfidptosis patterns in gastric cancer through bioinformatic assay

“…Hence, early identification of patients at high risk of GC is essential and vital. Increasing evidence from the extensive development of GC research suggests that GC is a complex disease with great heterogeneity and genetic variation [ 5 ]. Therefore, early precaution and identification of patients at high risk of developing GC from a genetic point of view will have a profound influence on the control of GC epidemiology.…”