Unique Genomic Alterations and Microbial Profiles Identified in Gastric Cancer Patients of African, European, and Asian Ancestry: A Novel Path for Precision Oncology

• Published in: Annals of surgery
• Main Authors: Abate, Miseker, Walch, Henry, Arora, Kanika, Vanderbilt, Chad M, Fei, Teng, Drebin, Harrison, Shimada, Shoji, Maio, Anna, Kemel, Yelena, Stadler, Zsofia K, Schmeltz, Joseph, Sihag, Smita, Ku, Geoffrey Y, Gu, Ping, Tang, Laura, Vardhana, Santosha, Berger, Michael F, Brennan, Murray F, Schultz, Nikolaus D, Strong, Vivian E
• Format: Journal Article
• Language: English
• Published: United States 29.06.2023
• ISSN: 1528-1140
• DOI: 10.1097/SLA.0000000000005970

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. 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. 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). 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.