Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

Jeffrey J. Tomaszewski, Jessica L. Cummings, Anil V. Parwani, Rajiv Dhir, Joel B. Mason, Joel B. Nelson, Dean J. Bacich, Denise S. O'Keefe

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


BACKGROUND A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (Figueiredo et al., J Natl Cancer Inst 2009; 101(6): 432-435). As tumor cells in culture proliferate directly in response to available folic acid, the goal of our study was to determine if there is a similar relationship between patient folate status, and the proliferative capacity of tumors in men with prostate cancer. METHODS Serum folate and/or prostate tissue folate was determined in 87 randomly selected patients undergoing surgery for prostate cancer, and compared to tumor proliferation in a subset. RESULTS Fasting serum folate levels were positively correlated with prostate tumor tissue folate content (n = 15; r = 0.577, P < 0.03). Mean serum folate was 62.6 nM (7.5-145.2 nM), 39.5% of patients used supplements containing folic acid (n = 86). The top quartile of patients had serum folates above 82 nM, six times the level considered adequate. Of these, 48% reported no supplement use. Among 50 patients with Gleason 7 disease, the mean proliferation index as determined by Ki67 staining was 6.17 ± 3.2% and 0.86 ± 0.92% in the tumors from patients in the highest (117 ± 15 nM) and lowest (18 ± 9 nM) quintiles for serum folate, respectively (P < 0.0001). CONCLUSIONS 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 patients had serum folate levels greater than sixfold adequate. Nearly half of these men reported no supplement use, suggesting either altered folate metabolism and/or sustained consumption of folic acid from fortified foods.

Original languageEnglish (US)
Pages (from-to)1287-1293
Number of pages7
Issue number12
StatePublished - Sep 2011
Externally publishedYes


  • B-vitamins
  • PSMA
  • folic acid
  • fortification

ASJC Scopus subject areas

  • Oncology
  • Urology


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