Abstract A169: Pathway-specific mutation profiles and single combination therapy survival outcomes in Hispanic/Latino and non-Hispanic White colorectal cancer patients

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide, disproportionately affecting Hispanic/Latino (H/L) patients due to a combination of genetic and environmental factors. Several treatment regimens are used for CRC, but it remains unclear whether molecular pathway alterations are associated with differential survival across treatment regimens. This study aims to determine whether pathway alterations in the TP53, WNT, RTK/RAS, PI3K/AKT, and TGF-β pathways differ between H/L and non-Hispanic White (NHW) individuals, and whether pathway mutation alterations are associated with survival outcomes among patients receiving commonly prescribed treatment regimens. We performed a bioinformatics analysis using publicly available CRC datasets to evaluate molecular 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 chemotherapy treatment (FOLFOX, FOLFIRI, bevacizumab, and immunotherapy). 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. A p-value <0.05 was considered significant. No significant differences in pathway mutation frequencies were observed between H/L and NHW patients with EOCRC or LOCRC within treatment groups. A trend toward higher RTK/RAS pathway mutation frequency was observed among LOCRC H/L patients compared with NHW patients (86.8% vs. 74.6%; p-value=0.068). Survival analysis identified several associations between pathway alterations and overall survival within treatment groups. A trend toward significance was observed in EOCRC H/L patients with TP53 pathway alterations, with bevacizumab improving overall survival (p-value=0.087). WNT alterations were associated with improved overall survival among LOCRC NHW patients treated with bevacizumab (p-value=0.012) and among patients not treated with FOLFOX (p-value=<0.001). Conversely, TGF-β pathway alterations were associated with worse overall survival among LOCRC NHW patients receiving FOLFIRI (p-value=<0.001). While pathway mutation frequencies were similar between H/L and NHW patients, specific pathway alterations were associated with differential overall survival across treatment groups. These findings suggest that specific pathway alterations within ethnic groups can guide treatment selection to improve overall survival. Enrique Velazquez Villarreal, MD, PhD, MPH, MS, Victor E. Morales. Pathway-specific mutation profiles and single combination therapy survival outcomes in Hispanic/Latino and non-Hispanic White colorectal cancer patients [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 A169.