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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- F st 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.

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