影响结直肠癌种族和民族存活率差异的分子、社会经济和临床因素。

IF 22.5 1区 医学 Q1 ONCOLOGY JAMA Oncology Pub Date : 2024-09-12 DOI:10.1001/jamaoncol.2024.3666
Mahmoud Yousef,Abdelrahman Yousef,Saikat Chowdhury,Mohammad M Fanaeian,Mark Knafl,Jennifer Peterson,Mohammad Zeineddine,Kristin Alfaro,Fadl Zeineddine,Drew Goldstein,Nicholas Hornstein,Arvind Dasari,Ryan Huey,Benny Johnson,Victoria Higbie,Alisha Bent,Bryan Kee,Michael Lee,Maria Pia Morelli,Van Karlyle Morris,Daniel Halperin,Michael J Overman,Christine Parseghian,Eduardo Vilar,Robert Wolff,Kanwal P Raghav,Michael G White,Abhineet Uppal,Ryan Sun,Wenyi Wang,Scott Kopetz,Jason Willis,John Paul Shen
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The relative contribution of variables to the disparity was determined using mediation analysis with sequential multivariate Cox regression models.\r\n\r\nMain Outcome\r\nOS, from diagnosis date and from start of first-line chemotherapy.\r\n\r\nResults\r\nThe 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%).\r\n\r\nConclusions\r\nThis 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. 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引用次数: 0

摘要

重要性在结直肠癌患者中已分别观察到总生存期(OS)的差异以及不同种族和民族驱动基因变异频率的差异;然而,这些差异是如何导致生存期差异的尚不清楚。目的量化分子、社会经济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之间的关系。设计、设置和参与者这项单中心队列研究是在一家三级癌症中心进行的,使用了自 1973 年 1 月 1 日至 2023 年 3 月 1 日期间诊断为结直肠癌的所有患者的相关数据。主要结果OS、从诊断日期起和从开始一线化疗起。结果研究人群中有 47 178 名患者(中位数[IQR]年龄,57.0[49-66]岁;20 465[43.4%]名女性和26 713[56.6%]名男性;3.0%为亚裔、8.7%为黑人、8.8%为西班牙裔、79.4%为白人),自初次诊断起的中位(IQR)随访时间为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(危险比[HR],1.16;95% CI,1.09-1.24;P<.001),而亚裔和西班牙裔患者的OS较好(HR,分别为0.66;95% CI,0.59-0.74;P<.001;和0.86;95% CI,0.81-0.92;P<.001)。如果仅限于转移性疾病患者,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年间OS差异的变化显示,亚裔、西班牙裔和白人患者之间的差异在缩小,但黑人患者和白人患者之间的差异在扩大(2008-2012年的HR为1.18;95% CI为1.07-1.31;2013-2017年的HR为1.24,95% CI为1.08-1.42;2018-2023年的HR为1.50;95% CI为1.20-1.87)。与白人患者相比,黑人患者一线化疗的生存结果更差(中位OS,18个月 vs 26个月;HR,1.30;95% CI,1.01-1.70)。在接受临床分子检测的7628名患者中,黑人患者中APC、KRAS和PIK3CA的变异频率较高(假发现率[FDR]分别为0.01;<0.001;和0.01),而白人患者中BRAF和KIT的变异频率较高(FDR分别为0.001和0.01)。通过中介分析发现,邻里社会经济状况是导致OS差异的最大因素(29%),其次是分子特征(微卫星不稳定性状态、KRAS变异和BRAF变异,10%)和肿瘤侧位(9%)。社会经济状况的影响最大,但只占差距的不到三分之一,肿瘤分子特征的影响也很大。需要进一步研究遗传血统和结直肠癌分子发病机制与化疗反应之间的关联。
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Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival.
Importance Disparity 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. Objective To 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 Participants This 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 Outcome OS, from diagnosis date and from start of first-line chemotherapy. Results The 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%). Conclusions This 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.
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来源期刊
JAMA Oncology
JAMA Oncology Medicine-Oncology
自引率
1.80%
发文量
423
期刊介绍: JAMA Oncology is an international peer-reviewed journal that serves as the leading publication for scientists, clinicians, and trainees working in the field of oncology. It is part of the JAMA Network, a collection of peer-reviewed medical and specialty publications.
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