Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival
Authors: Yousef Mahmoud , Yousef Abdelrahman , Chowdhury Saikat , Fanaeian Mohammad M. , Knafl Mark , Peterson Jennifer , Zeineddine Mohammad , Alfaro Kristin , Zeineddine Fadl , Goldstein Drew , Hornstein Nicholas , Dasari Arvind , Huey Ryan , Johnson Benny , Higbie Victoria , Bent Alisha , Kee Bryan , Lee Michael , Morelli Maria Pia , Morris Van Karlyle , Halperin Daniel , Overman Michael J. , Parseghian Christine , Vilar Eduardo , Wolff Robert , Raghav Kanwal P. , White Michael G. , Uppal Abhineet , Sun Ryan , Wang Wenyi , Kopetz Scott , Willis Jason , Shen John Paul 
Published: September 2024

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 &amp;lt;.001), whereas Asian and Hispanic patients had better OS (HR, 0.66; 95% CI, 0.59-0.74; P &amp;lt;.001; and 0.86; 95% CI, 0.81-0.92; P &amp;lt;.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 &amp;lt;.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; &amp;lt; 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.