Comparative genomic analysis of esophageal squamous cell carcinoma between Asian and Caucasian patient populations

TLDR

Esophageal squamous cell carcinoma shows distinct incidence and survival patterns across races, yet comparative genomic studies between populations have been lacking. The study aims to compare the genomic landscapes of ESCC in Asian versus Caucasian patients. Researchers sequenced 316 Chinese ESCC samples, merged them with TCGA data, and applied a robust computational strategy that adjusts for technical and biological confounders to conduct the cross‑population comparison. The comparative analysis identified CSMD3 mutations as prognostic in Asians, higher mutational frequencies of TP53, EP300, and NFE2L2 in Asian patients, and an association between NFE2L2 mutations and a nearby high‑Fst SNP, providing insights into racial disparities and a general computational framework.

Abstract

Esophageal squamous cell carcinoma is a major histological type of esophageal cancer, with distinct incidence and survival patterns among races. Although previous studies have characterized somatic mutations in this disease, a rigorous comparison between different patient populations has not been conducted. Here we sequence the samples of 316 Chinese patients, combine them with those from The Cancer Genome Atlas, and perform a comparative analysis between Asian and Caucasian patients. We find that mutated CSMD3 is associated with better prognosis in Asian patients. Applying a robust computational strategy that adjusts for both technical and biological confounding factors, we find that TP53, EP300, and NFE2L2 show higher mutational frequencies in Asian patients. Moreover, NFE2L2 mutations correlate with the allele status of a nearby high-Fst SNP, suggesting their potential interaction. Our study provides insights into the molecular basis underlying the striking racial disparities of this disease, and represents a general computational framework for such a cross-population comparison.