Abstract C101: Pathway-specific mutation profiles and their effect on overall survival in Hispanic/Latino and non-Hispanic White colorectal cancer patients receiving dual chemotherapy

Abstract

Colorectal cancer (CRC) disproportionately affects Hispanic/Latino (H/L) populations, yet little is known about survival outcomes across dual-treatment regimens in diverse populations. The study aims to identify differences in molecular pathway alterations between H/L and non-Hispanic White (NHW) patients and to determine whether these pathway alterations affect their overall survival when receiving dual chemotherapy. We performed a bioinformatics analysis using publicly available CRC datasets to evaluate pathway alterations, treatment exposure, and overall survival. We included 3457 patients in the analysis, including 272 H/L and 3185 NHW patients. Patients were stratified by early-onset CRC (EOCRC) and late-onset CRC (LOCRC) and dual chemotherapy treatment (FOLFOX + FOLFIRI, bevacizumab + FOLFIRI, bevacizumab + FOLFOX). Chi-square and Fisher’s exact tests were used to assess differences in mutation frequencies. Kaplan-Meier curves with log-rank testing were used to evaluate survival outcomes based on pathway alterations among H/L and NHW patients. Among LOCRC patients treated with FOLFOX + FOLFIRI, H/L patients had lower mutation frequencies in the PI3K/AKT pathway compared to NHW patients (26.1% vs. 34.8%; p-value=0.021). No significant difference in pathway alterations was found between H/L and NHW patients with EOCRC or LOCRC treated with bevacizumab + FOLFIRI or bevacizumab + FOLFOX. Survival analysis identified several associations between pathway alterations and overall survival within treatment groups. WNT pathway alterations were associated with increased overall survival in LOCRC H/L (p-value=<0.001) and NHW (p-value=<0.001) patients treated with FOLFOX + FOLFIRI. TGF-ß and RTK/RAS pathway alterations were associated with worse overall survival within EOCRC (p-value=0.012) and LOCRC (p-value=0.048) NHW patients treated with FOLFOX + FOLFIRI. H/L and NHW patients with WNT pathway alterations demonstrate improvements in overall survival. However, NHW patients with RTK/RAS and TGF-ß alterations demonstrate worse overall survival, highlighting the impact of specific mutation alterations on responsiveness to dual chemotherapy. Victor E. Morales, Enrique Velazquez Villarreal. Pathway-specific mutation profiles and their effect on overall survival in Hispanic/Latino and non-Hispanic White colorectal cancer patients receiving dual chemotherapy [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr C101.