Precision medicine relies on targeting specific somatic alterations present in a patient's tumor. However, the extent to which germline ancestry may influence the somatic burden of disease has received little attention. We estimated the genetic ancestry of non‐small‐cell lung cancer (NSCLC) patients and performed an in‐depth analysis of the influence of genetic ancestry on the evolutionary disease course. Compared with European Americans (EA), African Americans (AA) with lung adenocarcinoma (LUAD) were found to be significantly younger and smoke significantly less. However, LUADs from AAs exhibited a significantly higher somatic mutation burden, with a more pronounced tobacco carcinogen footprint and increased frequencies of alterations affecting cancer genes. Conversely, no significant differences were observed between lung squamous cell carcinomas (LUSC) from EAs and AAs. Our results suggest germline ancestry influences the somatic evolution of LUAD but not LUSC.

中文翻译：

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胚系起源影响肺腺癌的进化疾病进程。

精密医学依赖于靶向患者肿瘤中存在的特定体细胞变化。然而，种系谱系可能影响疾病的躯体负担的程度很少受到关注。我们评估了非小细胞肺癌（NSCLC）患者的遗传学背景，并对遗传学对进化病程的影响进行了深入分析。与欧洲裔美国人（EA）相比，发现患有肺腺癌（LUAD）的非洲裔美国人（AA）明显年轻，吸烟量明显减少。然而，来自AA的LUAD显示出明显更高的体细胞突变负担，更显着的烟草致癌物足迹和增加的改变频率影响癌症基因。反过来，在EA和AA的肺鳞状细胞癌（LUSC）之间未观察到显着差异。我们的结果表明种系祖先影响LUAD的体细胞进化，但不影响LUSC。