Tumor Molecular Features Contribute Substantially to Overall Survival Disparities Among Patients With Colorectal Cancer

A single-center cohort study found a substantial overall survival (OS) disparity with differing frequencies of driver gene variations, by race and ethnicity among patients with colorectal cancer.

This study included 47,178 patients diagnosed with colorectal cancer at a tertiary-level cancer center. Using mediation analysis with sequential multivariate Cox regression models, study authors sought to quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in OS. The primary outcome determined was OS from diagnosis date and start of first-line chemotherapy.

The median follow-up from initial diagnosis was 124 months, with a median OS of 55 months. Of the patients included, 79.4% were White, 8.8% were Hispanic, 8.7% were Black, and 3.0% were Asian. When compared to White patients, Black patients had a worse OS (hazard ratio [HR], 1.16; P < .001), while Asian and Hispanic patients both had better OS (HR, 0.66; P < .001, and HR, 0.86; P < .001, respectively). When only counting patients with metastatic disease, the greatest disparity among OS was between White patients and Black patients (HR, 1.2; P < .001). While the disparity between Asian, Hispanic, and White patients decreased over 20 years, the disparity between Black and White patients increased. Additionally, the median OS for first-line chemotherapy was 18 months for Black patients compared to 26 months for White patients (HR, 1.30).

There were 7628 patients who underwent clinical molecular testing. Of those patients, there was a higher frequency of APC, KRAS, and PIK3CA mutations among Black patients, and a higher frequency of BRAF and KIT mutations among White patients. The greatest contributor to OS disparity was neighborhood socioeconomic status (28%), followed by molecular characteristics (microsatellite instability status, KRAS variation, and BRAF variation, 10%) and tumor sidedness (9%).

Study authors concluded that while “socioeconomic status had the largest contribution” to OS disparities, it “accounted for less than one-third of the disparity, with substantial contribution from tumor molecular features.” They added that “further study of the associations of genetic ancestry and the molecular pathogenesis of colorectal cancer with chemotherapy response is needed.”

Source:

Yousef M, Yousef A, Chowdhury S, et al. Molecular, socioeconomic, and clinical factors affecting racial and ethnic disparities in colorectal cancer survival. JAMA Oncol. Published online September 12, 2024. doi:10.1001/jamaoncol.2024.3666