Abstract
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a cancer with a poor prognosis, characterized by distinct geographical distribution and family clustering. AIM: To investigate if ethnic differences (Han vs Kazakh) cause molecular variations in ESCC patients via genomic sequencing 299 samples. METHODS: Here, we sequenced samples from 299 ESCC patients collected from Henan Key Laboratory for Esophageal Cancer Research and National Key Laboratory of Metabolic Dysregulation and Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Zhengzhou University, including Han and Kazakh ethnic groups, and performed a genomic comparative analysis of these two ethnic cohorts. RESULTS: ESCC patients of Kazakh ethnicity present with a later age of onset compared to Han. Kazakh patients exhibit a slightly higher tumor mutation burden compared to their Han counterparts. Three genes GIGYF1, CACNA1D, and ACOT11 exhibited mutation frequencies threefold higher in Kazakh patients than in Han. This enrichment may be associated with Kazakhs' adaptation to cold climates and consumption of high-calorie diets. Among Han patients, the apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide (APOBEC)-associated single base substitutions (SBS) 13 mutational signature is more prevalent, whereas SBS6, indicative of DNA mismatch repair deficiency, is more common in Kazakh patients. Additionally, Han Chinese patients with APOBEC-enriched tumors exhibit a significantly higher mutation load than those without. Moreover, patients lacking the APOBEC signature demonstrate superior survival probability compared to the APOBEC-enriched group. CONCLUSION: Living environment and diet are major factors in the development of ESCC. Genomic difference may provide guidance for the formulation of clinical treatment plans for ESCC from different ethnics regions.