Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.

食管鳞状细胞癌 (ESCC) 的发病率存在显着差异，已知的生活方式和环境风险因素无法完全解释这一点。据推测，未知的外源性暴露可能是造成这种情况的原因。在这里，我们将突变特征分析领域与癌症流行病学相结合，以研究来自八个不同发病率国家的 552 个 ESCC 基因组。所有研究国家的突变概况都相似。确定了烟草、酒精、鸦片和种系变异的特定突变特征与 ESCC 风险因素之间的关联，对突变负担的影响适度。我们没有发现表明能够解释 ESCC 发病率差异的外源性暴露的突变特征的证据。载脂蛋白 B mRNA 编辑酶，