Abstract C034: Genetic ancestry in Colombian men with suspected prostate cancer and its association with novel early detection biomarkers

Abstract In Colombia, prostate cancer is the most common malignancy and the leading cause of cancer death among men, with an incidence rate of 52.6 per 100,000. These trends highlight the need for effective strategies to improve early detection and timely clinical management. As a biologically heterogeneous disease, prostate cancer shows marked variability in incidence, progression, and outcomes across ancestral backgrounds. Although disparities in disease burden are well documented, the biological mechanisms underlying ancestry-related differences remain poorly understood, particularly in underrepresented populations such as those in Latin America. The Colombian population presents a complex admixture of European, Native American, and African ancestries, resulting in high genetic diversity with implications for tumor biology and biomarker performance. Yet, the influence of ancestry on prostate cancer risk and molecular features remains largely unexplored in Latino populations. In a previous transcriptomic analysis, we identified 29 differentially expressed genes (DEGs) as candidate biomarkers for early prostate cancer detection in 75 Colombian men with suspected malignancy. DEG selection considered clinical variables such as age, histopathological diagnosis, and PSA levels. Here, we examined the relationship between inferred genetic ancestry and expression of these biomarkers. Ancestry was estimated using RNA-seq–derived variants. From 47,723 SNPs, quality control in PLINK retained 8,818 high-quality SNPs. Global ancestry proportions: European (EUR), Native American (NAM), and African (AFR), were inferred using ADMIXTURE with K = 3 reference populations. The cohort’s average ancestry was 50% EUR, 41% NAM, and 7% AFR. Of the 29 DEGs, nine were positively correlated with European ancestry: ACY1, ALCAM, APOE, EEF1A2, FASN, GOLM1, HPN, PCA3 , and PKP3 . Notably, FASN has been previously associated with ancestry-linked expression differences, suggesting a role for lipid metabolism pathways shaped by genetic background. PCA3 , a widely used diagnostic marker, has shown higher performance in men of European descent, raising concerns about its utility in admixed populations. The other genes have known roles in tumorigenesis but have not been linked to ancestry, opening avenues for investigating novel regulatory mechanisms. An exploratory analysis revealed that BICD1, NAALADL2, and VSTM2L were associated with African ancestry, although they were not identified among the original DEGs, possibly due to underrepresentation in the cohort. Collectively, these findings suggest that genetic ancestry may influence the expression of biomarkers associated with prostate cancer. Integrating molecular data informed by ancestry could improve biomarker discovery and support the development of more precise and equitable strategies for early detection in admixed populations. Further validation in larger and more diverse cohorts is needed. Citation Format: Dayanne M. Rodríguez Hernández, Alba L. Cómbita, Jovanny Zabaleta, Rafael S. Parra-Medina, Yina T. Zambrano, Carmen L. Roa, Carlos A. Orozco, Alvaro Gutierrez, Mateo Barros. Genetic ancestry in Colombian men with suspected prostate cancer and its association with novel early detection biomarkers [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C034.