Abstract C089: Modulation of DNA methylation by plasma folate and heavy metals in relation to prostate cancer aggressiveness

Abstract Background: Significant racial disparities exist in prostate cancer (PCa), particularly among African American (AA) men, who consume fewer green vegetables and face prolonged environmental exposure such as arsenic. However, the role of DNA methylation in folate and arsenic metabolism in PCa formation and progression remains unclear, especially among AA men. Methods: Blood DNA methylation was analyzed in 117 PCa cases from the North Carolina-Louisiana Prostate Cancer Project (PCaP), including AAs and European Americans (EAs). PCa aggressiveness was classified using clinical stage, Gleason score, and PSA level. Plasma folate and folic acid were quantified and categorized into quartiles. Univariate and multivariate analyses assessed the effect of plasma folate and PCa aggressiveness on DNA methylation profiles, adjusting for age, race, smoking, urinary heavy metal concentrations, and cell compositions. Results: Significant separation of DNA methylation profiles by race was observed at baseline. Variations in dietary folate, heavy metal exposure, cell compositions, and smoking histories significantly affected DNA methylation profiles. When examining the methylation changes associated with metal exposure and PCa aggressiveness, arsenic and cadmium showed significant interactions with aggressive PCa. Plasma folic acid had the most influence on DNA methylation profiles compared to unmetabolized folic acid and synthetic folates. Conclusions: Plasma folic acid levels interact with PCa aggressiveness, suggesting nutritional status is important to prevent aggressive outcomes in PCa. Additionally, arsenic exposure significantly contributes to the methylation profiles, highlighting the need to reduce arsenic exposure among high-risk populations. Citation Format: Ping-Ching Hsu, Se-Ran Jun, L. Joseph. Su. Modulation of DNA methylation by plasma folate and heavy metals in relation to prostate cancer aggressiveness [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 C089.