已知不同种族和民族的结直肠癌 (CRC) 发病率和结果存在差异。其中一些差异可能是由肿瘤的分子变化介导的，这些变化在人群中以不同的速度发生。遗传血统是对种族和民族的补充，可以克服数据缺失问题并更好地捕获混合人群中的遗传相似性。我们的目的是确定与遗传血统和推算种族和民族相关的体细胞突变和肿瘤基因表达差异。使用 Tempus xT NGS 648 基因组和全外显子组捕获 RNA 测序对 8454 名主要晚期 CRC 患者进行测序。使用祖先信息标记估计了五个大陆群体——非洲（AFR）、美洲土著（AMR）、东亚（EAS）、欧洲（EUR）和南亚（SAS）——的遗传祖先比例。为了解决数据差距，对种族和族裔类别进行了估算，最终分配了 952 名西班牙裔/拉丁裔、420 ​​名非西班牙裔 (NH) 亚洲人、1061 名新罕布什尔州黑人和 5763 名新罕布什尔州白人。我们评估了遗传血统比例、推算的种族和民族类别与相关 CRC 基因和 2608 表达谱以及 1957 共识分子亚型 (CMS) 中的体细胞突变的关联。AFR 血统的增加与 APC 体细胞突变的几率较高相关、KRAS 和 PIK3CA 以及 BRAF 突变的几率较低。此外，EAS 血统增加与 KRAS 突变几率较低相关，欧洲裔与 BRAF 突变几率较高相关，西班牙裔/拉丁裔类别与 BRAF 突变几率较低相关。较高的 AFR 血统和 NH 黑人类别与较高的 CMS3 发生率相关，而较高比例的西班牙裔/拉丁裔患者表现出不确定的 CMS 分类。CRC 肿瘤突变频率和基因表达的分子差异可能是观察到的种族和民族差异的基础确定。 AFR 血统与 KRAS 突变增加的关联与 NH 黑人患者中较高的 CMS3 亚型率一致。西班牙裔/拉丁裔患者中不确定 CMS 的增加表明，亚型分类方法可以受益于患者多样性的增强。© 2024。作者。

There are known disparities in incidence and outcomes of colorectal cancer (CRC) by race and ethnicity. Some of these disparities may be mediated by molecular changes in tumors that occur at different rates across populations. Genetic ancestry is a measure complementary to race and ethnicity that can overcome missing data issues and better capture genetic similarity in admixed populations. We aimed to identify somatic mutations and tumor gene expression differences associated with both genetic ancestry and imputed race and ethnicity.Sequencing was performed with the Tempus xT NGS 648-gene panel and whole exome capture RNA-Seq for 8454 primarily late-stage CRC patients. Genetic ancestry proportions for five continental groups-Africa (AFR), American indigenous (AMR), East Asia (EAS), Europe (EUR), and South Asia (SAS)-were estimated using ancestry informative markers. To address data gaps, race and ethnicity categories were imputed, resulting in assignments for 952 Hispanic/Latino, 420 non-Hispanic (NH) Asian, 1061 NH Black, and 5763 NH White individuals. We assessed association of genetic ancestry proportions and imputed race and ethnicity categories with somatic mutations in relevant CRC genes and in 2608 expression profiles, as well as 1957 consensus molecular subtypes (CMS).Increased AFR ancestry was associated with higher odds of somatic mutations in APC, KRAS, and PIK3CA and lower odds of BRAF mutations. Additionally, increased EAS ancestry was associated with lower odds of mutations in KRAS, EUR with higher odds in BRAF, and the Hispanic/Latino category with lower odds in BRAF. Greater AFR ancestry and the NH Black category were associated with higher rates of CMS3, while a higher proportion of Hispanic/Latino patients exhibited indeterminate CMS classifications.Molecular differences in CRC tumor mutation frequencies and gene expression that may underlie observed differences by race and ethnicity were identified. The association of AFR ancestry with increased KRAS mutations aligns with higher CMS3 subtype rates in NH Black patients. The increase of indeterminate CMS in Hispanic/Latino patients suggests that subtype classification methods could benefit from enhanced patient diversity.© 2024. The Author(s).