ImportanceDisparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown.ObjectiveTo quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer.Design, Setting, and ParticipantsThis single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023. The relative contribution of variables to the disparity was determined using mediation analysis with sequential multivariate Cox regression models.Main OutcomeOS, from diagnosis date and from start of first-line chemotherapy.ResultsThe study population of 47 178 patients (median [IQR] age, 57.0 [49-66] years; 20 465 [43.4%] females and 26 713 [56.6%] males; 3.0% Asian, 8.7% Black, 8.8% Hispanic, and 79.4% White individuals) had a median (IQR) follow-up from initial diagnosis of 124 (174) months and OS of 55 (145) months. Compared with White patients, Black patients had worse OS (hazard ratio [HR], 1.16; 95% CI, 1.09-1.24; P <.001), whereas Asian and Hispanic patients had better OS (HR, 0.66; 95% CI, 0.59-0.74; P <.001; and 0.86; 95% CI, 0.81-0.92; P <.001, respectively). When restricted to patients with metastatic disease, the greatest disparity was between Black patients compared with White patients (HR, 1.2; 95% CI, 1.06-1.37; P <.001). Evaluating changes in OS disparity over 20 years showed disparity decreasing among Asian, Hispanic, and White patients, but increasing between Black patients and White patients (HRs, 1.18; 95% CI, 1.07-1.31 for 2008-2012; 1.24, 95% CI, 1.08-1.42 for 2013-2017; and 1.50; 95% CI, 1.20-1.87 for 2018-2023). Survival outcomes for first-line chemotherapy were worse for Black patients compared with White patients (median OS, 18 vs 26 months; HR, 1.30; 95% CI, 1.01-1.70). Among 7628 patients who had clinical molecular testing, APC, KRAS, and PIK3CA showed higher variant frequency in Black patients (false discovery rate [FDR], 0.01; < 0.001; and 0.01, respectively), whereas BRAF and KIT were higher among White patients (FDR, 0.001 and 0.01). Mediation analysis identified neighborhood socioeconomic status as the greatest contributor to OS disparity (29%), followed by molecular characteristics (microsatellite instability status, KRAS variation and BRAF variation, 10%), and tumor sidedness (9%).ConclusionsThis single-center cohort study identified substantial OS disparity and differing frequencies of driver gene variations by race and ethnicity. Socioeconomic status had the largest contribution but accounted for less than one-third of the disparity, with substantial contribution from tumor molecular features. Further study of the associations of genetic ancestry and the molecular pathogenesis of colorectal cancer with chemotherapy response is needed.

中文翻译：

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影响结直肠癌生存率种族和民族差异的分子、社会经济学和临床因素


重要性 在结直肠癌患者中分别观察到总生存期 （OS） 的差异以及种族和民族驱动基因变异频率的差异;然而，这些差异如何导致生存差异尚不清楚。目的量化分子、社会经济学和临床协变量与结直肠癌患者总生存期的种族和民族差异的相关性。设计、设置和参与者这项单中心队列研究是在三级癌症中心进行的，使用了 1973 年 1 月 1 日至 2023 年 3 月 1 日期间所有被诊断患有结直肠癌的患者的相关数据。使用顺序多变量 Cox 回归模型的中介分析确定变量对差异的相对贡献。主要结果OS，从诊断日期到一线化疗开始。结果研究人群 47 178 例患者 （中位 [IQR] 年龄，57.0 [49-66] 岁;20 465 [43.4%] 女性和 26 713 [56.6%] 男性;3.0% 亚裔，8.7% 黑人，8.8% 西班牙裔和 79.4% 白人个体）从初始诊断开始的中位 （IQR） 随访为 124 （174） 个月，OS 为 55 （145） 个月。与白人患者相比，黑人患者的 OS 较差 （风险比 [HR]，1.16;95% CI，1.09-1.24;P <。001），而亚裔和西班牙裔患者的 OS 更好 （HR，0.66;95% CI，0.59-0.74;P <。001;和 0.86;95% CI，0.81-0.92;P <。001）。当仅限于转移性疾病患者时，黑人患者与白人患者之间的差异最大（HR，1.2;95% CI，1.06-1.37;P <。001). 评估 20 年 OS 差异的变化显示，亚裔、西班牙裔和白人患者之间的差异缩小，但黑人患者和白人患者之间的差异增加（HRs，1.18;95% CI，2008-2012 年 1.07-1.31;1.24,95% CI，2013-2017 年 1.08-1.42;以及 1.50;95% CI，2018-2023 年 1.20-1.87）。与白人患者相比，黑人患者一线化疗的生存结局更差（中位 OS，18 个月 vs 26 个月;心率，1.30;95% CI，1.01-1.70）。在接受临床分子检测的 7628 名患者中，APC、KRAS 和 PIK3CA 在黑人患者中表现出更高的变异频率（假发现率 [FDR]，分别为 0.01;< 0.001;和 0.01），而 BRAF 和 KIT 在白人患者中更高（FDR，0.001 和 0.01）。中介分析确定社区社会经济地位是 OS 差异的最大贡献者 （29%），其次是分子特征 （微卫星不稳定状态、KRAS 变异和 BRAF 变异，10%） 和肿瘤偏侧 （9%）。结论这项单中心队列研究确定了种族和民族之间巨大的 OS 差异和驱动基因变异的不同频率。社会经济地位的贡献最大，但占差异的不到三分之一，其中肿瘤分子特征的贡献很大。需要进一步研究结直肠癌的遗传祖先和分子发病机制与化疗反应的关联。