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Comment
. 2024 Nov 1;10(11):1519-1529.
doi: 10.1001/jamaoncol.2024.3666.

Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival

Mahmoud Yousef  1 , Abdelrahman Yousef  1 , Saikat Chowdhury  1 , Mohammad M Fanaeian  1 , Mark Knafl  2 , Jennifer Peterson  1 , Mohammad Zeineddine  1 , Kristin Alfaro  1 , Fadl Zeineddine  1 , Drew Goldstein  3 , Nicholas Hornstein  4 , Arvind Dasari  1 , Ryan Huey  1 , Benny Johnson  1 , Victoria Higbie  1 , Alisha Bent  1 , Bryan Kee  1 , Michael Lee  1 , Maria Pia Morelli  1 , Van Karlyle Morris  1 , Daniel Halperin  1 , Michael J Overman  1 , Christine Parseghian  1 , Eduardo Vilar  5 , Robert Wolff  1 , Kanwal P Raghav  1 , Michael G White  6 , Abhineet Uppal  6 , Ryan Sun  7 , Wenyi Wang  8 , Scott Kopetz  1 , Jason Willis  1 , John Paul Shen  1
Affiliations
Comment

Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival

Mahmoud Yousef et al. JAMA Oncol. .

Abstract

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Huey reported personal fees from Clinical Care Targeted Communications, Vizient, and Aptitude Health outside the submitted work. Dr Johnson reported grants from Bristol Myers Squibb, Syntrix, Gritstone, and personal fees from Incyte, Taiho Oncology, and Iota outside the submitted work. Dr Kee reported equity in Medtronic outside the submitted work. Dr Lee reported personal fees from Johnson & Johnson, BioNTech, Imvax, G1 Therapeutics, Delcath Systems, Bayer Health, and grants from Arcus Biosciences, Erasca, Repare Therapeutics, Merck, TriSalus Life Sciences, Boehringer Ingelheim, Xilis, and EpimAb Biotherapeutics outside the submitted work. Dr Morris reported institutional research funding from Bristol Myers Squibb, Pfizer Research, REDX Pharma, BioNTech, and Regeneron outside the submitted work. Dr Halperin grants from Novartis, ITM, RayzeBio, Camurus, Thermo Fisher Scientific, Exelixis, Harpoon Tx, Chimeric Tx, Crinetics, and Amryt Pharma outside the submitted work. Dr Vilar reported research funds and/or advisory board fees from Guardant Health, Nouscom, Rising Tide Foundation, and Recursion Pharma outside the submitted work. Dr Uppal reported personal fees from Bayer outside the submitted work. Dr Wang reported grants from Curis outside the submitted work. Dr Kopetz reported ownership in Lutris, Frontier Medicines, and Navire, and consulting fees from Genentech, Merck, Boehringer Ingelheim, Bayer Health, Lutris, Pfizer, Mirati Therapeutics, Flame Biosciences, Carina Biotech, Frontier Medicines, Replimune, Bristol Myers Squibb, Medarex, Amgen, Tempus, Harbinger Oncology, Zentalis, AVEO, Tachyon Therapeutics, Agenus, Revolution Medicines, Kestrel Therapeutics, Regeneron, and Roche, and research for Sanofi, Guardant Health, Genentech/Roche, EMD Serono, MedImmune, Novartis, Amgen, Lilly, Daiichi Sankyo, Pfizer, Boehringer Ingelheim, BridgeBio, Cardiff, Jazz, Zentalis, and Mirati outside the submitted work. Dr Shen reported grants from CPRIT during the conduct of the study; and research funding from Celsius Therapeutics, BostonGene, NaDeNo Nanoscience, and Engine Biosciences outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Differences in Colorectal Cancer Overall Survival (OS) and Temporal Trends, by Race and Ethnicity
Figure 2.
Figure 2.. ADI Scores, Chemotherapy Survival Outcomes, and Gene Variant Rates Among Patients With Colorectal Cancer, by Race and Ethnicity
OS from start of first-line chemotherapy includes patients who received chemotherapy at the MD Anderson Cancer Center since January 2016 (n = 850). The volcano plot shows differences in driver gene variant frequencies in Black patients compared with White patients. Frequencies reported are the percentage of the total for each race group, P values reported are for χ2 test results, adjusted for false discovery rate (only statistically significant P values are shown). ADI indicates area deprivation index, and OS, overall survival.
Figure 3.
Figure 3.. Univariate and Multivariate Cox Regression Models for Overall Survival of Colorectal Cancer
ADI indicates area deprivation index; CCI, Charlson Comorbidity Index; ECOG, Eastern Cooperative Oncology Group; MSI-H, microsatellite instability-high; and OS, overall survival.
Figure 4.
Figure 4.. Mediation Analysis Results and Percentage Change in Racial and Ethnic Differences in Overall Survival in the Multivariate Models Sequence
ADI indicates area deprivation index; HR, hazard ratio; ECOG, Eastern Cooperative Oncology Group, MSI, microsatellite instability status.
See this image and copyright information in PMC

Comment on

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