Abstract A058: Plasma folate and folic acid status in relation to prostate cancer aggressiveness: Insights into racial disparities from the PCaP study

Background: African American men face a disproportionately high burden of aggressive prostate cancer compared to their White counterparts. While environmental exposures such as arsenic have been studied as potential risk factors, the role of nutritional status—particularly plasma folate and folic acid levels—in modifying prostate cancer aggressiveness remains poorly understood. This study evaluates whether plasma folate and folic acid are associated with prostate cancer aggressiveness and whether their effects differ by exposure levels and race. Methods: Data were analyzed from 1,031 prostate cancer cases in the North Carolina-Louisiana Prostate Cancer Project (PCaP), including both Black and White men. Prostate cancer aggressiveness was classified using clinical stage, Gleason score, and PSA level. Plasma folate and folic acid were quantified from blood samples and categorized into quartiles. Multivariable logistic regression models assessed associations between plasma biomarker levels and high-aggressive prostate cancer, adjusting for age, race, waist-to-hip ratio, smoking, alcohol use, screening history, and study site. Dose-response and race-specific trends were explored by assessing interaction effects. Results: A non-linear relationship was observed between plasma folate and prostate cancer aggressiveness. Compared to men in the lowest quartile, those in moderate plasma folate levels (Q2–Q3) had lower odds of high-aggressive disease, while men in the highest quartile (Q4) had elevated odds (adjusted OR=2.29, 95% CI: 1.13–4.71). A similar U-shaped trend was observed with plasma folic acid: moderate levels were associated with lower odds of aggressive cancer, but both low and high extremes were associated with increased odds. Interaction model showed that among Black men, the association between high plasma folate and increased prostate cancer aggressiveness was more pronounced compared to White men, highlighting a possible differential vulnerability by race. Conclusions: Plasma folate and folic acid levels demonstrate non-linear associations with prostate cancer aggressiveness, suggesting that both deficiency and excess may contribute to worse outcomes. These findings underscore the need for precision nutritional guidance and further investigation into metabolic and racial differences in folate utilization as contributors to prostate cancer disparities. Citation Format: MinJae Lee, Joseph Su, Ping-ching Hsu. Plasma folate and folic acid status in relation to prostate cancer aggressiveness: Insights into racial disparities from the PCaP study [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 A058.