Submitted to: The Prostate Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/8/2012
Publication Date: 9/15/2011
Citation: Tomaszewski, J.J., Cummings, J.L., Parwani, A., Dhir, R., Mason, J.B., Nelson, J.B., Bachich, D.J., O'Keefe, D.S. 2011. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate. The Prostate Journal. 71(12):1287-1293. Interpretive Summary: A recent clinical trial revealed that supplementation with B-vitamin folic acid is associated with an increased incidence of prostate cancer. The present study evaluates folate levels in the blood and prostate of men with prostate cancer compared to men with normal prostates. Folate concentrations were measured in 86 men with prostate cancer and from 32 cancer-free controls. The blood and prostate folate concentrations were significantly higher at all age ranges in men with prostate cancer compared to cancer-free men. Among men with prostate cancer, blood folate levels correlated with the folate levels in the cancer itself. This is the first report that demonstrates a correlation between blood folate levels with those in prostate cancers. Also, there was a correlation between the rate of cell proliferation in the cancers with higher serum folate concentrations. Unexpectedly, more than 25% of the men with prostate cancer had blood folate concentrations 6-fold greater than considered adequate, suggesting either regular supplement use and/or altered folate metabolism.
Technical Abstract: Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from cancer-free organ donors. Experimental Design: Serum and/or prostate tissue folate concentration were measured in 86 patients undergoing radical prostatectomy, and from 32 cancer-free organ donors. Expression of Ki67 and PSMA were assessed in a subset of these tissues. Results: Mean serum folate concentrations were significantly higher at all age ranges in men with prostate cancer compared to cancer-free organ donors (p<0.002). Fasting serum folate levels were positively correlated with prostate cancer tissue folate content (n= 15; Spearman Correlation r= 0.577, p<0.03). Mean tissue folate levels in prostate cancers were also significantly higher than in cancer-free prostates from age-matched organ donors (p<0.02). Among patients with Gleason Score 7 disease, the mean proliferation index was 6.17 +/- 3.2% and 0.86 +/- 0.92% in patients in the highest (117 +/- 15nM) and lowest (18 +/- 9nM) quintiles for serum folate, respectively (p<0.0001). Conclusions: To our knowledge, this is the first report of a positive correlation between serum folate and prostate cancer tissue folate. Increased cancer cell proliferation in men with higher serum folate concentrations is consistent with an increase in prostate cancer incidence observed with folate supplementation. Unexpectedly, more than 25% of the prostate cancer cohort had a serum folate concentration 6-fold greater than considered adequate, suggesting either regular supplement use and/or altered folate metabolism.