title: Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate.
abstract: 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.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Tomaszewski
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Cummings
authors.forename: Anil V
authors.initials: AV
authors.lastname: Parwani
authors.forename: Rajiv
authors.initials: R
authors.lastname: Dhir
authors.forename: Joel B
authors.initials: JB
authors.lastname: Mason
authors.forename: Joel B
authors.initials: JB
authors.lastname: Nelson
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Bacich
authors.forename: Denise S
authors.initials: DS
authors.lastname: O'Keefe
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000097:blood* / Q000473:pathology*; D049109:Cell Proliferation; D005215:Fasting / Q000097:blood; D005492:Folic Acid / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015994:Incidence; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011471:Prostatic Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D013194:Staining and Labeling
chemical_list: D019394:Ki-67 Antigen; D005492:Folic Acid