Ethnic genomic diversity in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) remains one of the most lethal malignancies worldwide, with pronounced geographic and ethnic disparities in incidence and outcomes. Rapid advances in genome-wide and sequencing technologies have revealed population-specific mutation spectra and risk loci, highlighting the interplay between inherited susceptibility and environmental exposures. The recent Han-Kazakh whole-exome study provided compelling evidence that ethnic background can shape the mutational landscape of Chinese ESCC, identifying population-restricted alterations such as GIGYF1 and distinct mutational signatures related to apolipoprotein B mRNA-editing enzyme catalytic polypeptide activity. These findings underscore the biological consequences of ethnic heterogeneity but also expose critical gaps: Most available data derive from limited Asian cohorts, cross-sectional designs, and coding-region analyses, leaving African, Central Asian, and multi-ancestry populations underrepresented and the functional relevance of non-coding and epigenetic changes unresolved. Building on this foundation, the present review synthesizes current genomic, transcriptomic, and epigenomic evidence across diverse ethnic groups to delineate shared and population-specific drivers of ESCC carcinogenesis. We emphasize how polymorphisms in alcohol-metabolizing enzymes (ADH1B, ALDH2), DNA-repair and oxidative-stress pathways, and immune-related networks interact with lifestyle and environmental factors to influence tumor initiation and progression. By integrating multi-ethnic multi-omics data, we highlight emerging biomarkers and therapeutic targets that may inform ancestry-aware screening, risk stratification, and individualized treatment strategies. Bridging these ethnic and molecular divides is essential for translating genomic discoveries into equitable precision oncology for ESCC.