Association Between Dietary Folate and Prostate Cancer Aggressiveness Among African Americans and European Americans

<b>Background:</b> Despite the confirmed beneficial effects on preventing neural tube defects, concerns about high intakes of synthetic folate, or folic acid, in promoting cancer progression have been raised. This study evaluated the association between folate intake and prostate cancer (PCa) aggressiveness among African-American (AA) and European-American (EA) males. <b>Methods:</b> This study included 722 AA and 775 EA men with prostate cancer. Folate intake (dietary folate equivalent (DFE), synthetic folate, natural folate) was estimated using the National Cancer Institute Dietary History Questionnaire and detailed dietary supplement use questionnaire. Analyses included univariable comparisons of demographic and clinical characteristics of the two racial groups using the <i>t</i>-test or its non-parametric counterpart, the Wilcoxon test for continuous variables, and the Chi-square test for categorical variables. Logistic regression analysis was performed to evaluate the associations of each source of folate intake with PCa aggressiveness. Interaction effects between folate intake levels and racial groups were tested to evaluate if the association between folate intake and PCa differed by racial groups. <b>Results:</b> A greater proportion of AA subjects were diagnosed with high PCa aggressiveness compared to EAs (31.6% vs. 21.7%; <i>p</i> < 0.001). Both AAs and EAs had associations between decreased DFE intake and PCa aggressiveness after adjusting for covariates. Among AAs, men with the highest quartile levels of synthetic folate intake had higher odds of high-aggressive PCa compared to those with the lowest levels of intake (adj. OR = 1.39; <i>p</i> = 0.27), while the reversed association became stronger among EAs (adj. OR = 0.62; <i>p</i> = 0.14). <b>Conclusions:</b> The association between folate intake and prostate cancer aggressiveness appears to be source-specific and modified by race. These findings highlight the need for population-informed nutritional guidance and further investigation into nutrient-gene and dietary pattern interactions in prostate cancer progression.