Background/Objectives: This study aims to characterize PI3K and TP53 pathway alterations in Hispanic/Latino patients with early-onset colorectal cancer (CRC), focusing on potential differences compared to non-Hispanic White (NHW) patients. Understanding these differences may shed light on the molecular basis of CRC health disparities. Methods: Using cBioPortal, we conducted a bioinformatics analysis to evaluate CRC mutations within the PI3K and TP53 pathways. CRC cases were stratified by age and ethnicity: (1) early-onset (<50 years) versus late-onset (≥50 years) and (2) early-onset in Hispanic/Latino patients compared to early-onset in NHW patients. Mutation frequencies were assessed using descriptive statistics, with chi-squared tests comparing proportions between early-onset Hispanic/Latino and NHW groups. Kaplan-Meier survival curves were generated to assess overall survival for early-onset Hispanic/Latino patients, stratified by the presence or absence of PI3K and TP53 pathway alterations. Results: Significant differences were noted when comparing early-onset CRC in Hispanic/Latino patients to early-onset CRC in NHW patients. PI3K pathway alterations were more prevalent in early-onset CRC among Hispanic/Latino patients (90.5% vs. 41.5%, p = 9.279e-5), with mTOR alterations also significantly higher in this group (14.3% vs. 1.5%, p = 0.043). No significant differences were observed between early-onset and late-onset CRC cases within the Hispanic/Latino cohort. Additionally, Hispanic/Latino patients with early-onset CRC showed improved clinical outcomes when TP53 pathway alterations were present (p =5.4e-4). Conclusions: These findings highlight the distinct role of PI3K and TP53 pathway disruptions in early-onset CRC among Hispanic/Latino patients, suggesting that pathway-specific mechanisms may drive cancer health disparities. Insights from this study could inform the potential development of precision medicine approaches and targeted therapies aimed at addressing these disparities and improving outcomes for diverse patient populations.

The authors have declared no competing interest.

This study was funded by grants from Cancer Control and Population Sciences Program (P30CA033572) within the City of Hope Comprehensive Cancer Center.

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The study used only openly available human data that is originally located at cBioPortal.

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All data produced in the present study are available upon reasonable request to the authors and can be found online at cBioPortal.

https://www.cbioportal.org/