title: Dietary influences on tissue concentrations of phytanic acid and AMACR expression in the benign human prostate.
abstract: BACKGROUND
  Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in fatty acid metabolism that is markedly over-expressed in virtually all prostate cancers (PCa), relative to benign tissue. One of AMACR's primary substrates, phytanic acid, is derived predominately from red meat and dairy product consumption. Epidemiological evidence suggests links between dairy/red meat intake, as well as phytanic acid levels, and elevated PCa risk. This study investigates the relationships among dietary intake, serum and tissue concentrations of phytanic acid, and AMACR expression (mRNA and protein) in the histologically benign human prostate.
  
  
  METHODS
  Men undergoing radical prostatectomy for the treatment of localized disease provided a food frequency questionnaire (n = 68), fasting blood (n = 35), benign fresh frozen prostate tissue (n = 26), and formalin-fixed paraffin-embedded (FFPE) sections (n = 67). Serum and tissue phytanic acid concentrations were obtained by gas chromatography-mass spectrometry. We extracted RNA from epithelial cells using laser capture microdissection and quantified mRNA expression of AMACR and other genes involved in the peroxisomal phytanic acid metabolism pathway via qRT-PCR. Immunohistochemistry for AMACR was performed on FFPE sections and subsequently quantified via digital image analysis. Associations between diet, serum, and tissue phytanic acid levels, as well as AMACR and other gene expression levels were assessed by partial Spearman correlation coefficients.
  
  
  RESULTS
  High-fat dairy intake was the strongest predictor of circulating phytanic acid concentrations (r = 0.35, P = 0.04). Tissue phytanic acid concentrations were not associated with any dietary sources and were only weakly correlated with serum levels (r = 0.29, P = 0.15). AMACR gene expression was not associated with serum phytanic acid (r = 0.13, P = 0.47), prostatic phytanic acid concentrations (r = 0.03, P = 0.88), or AMACR protein expression (r = -0.16, P = 0.20).
  
  
  CONCLUSIONS
  Our data underscore the complexity of the relationship between AMACR and its substrates and do not support the unifying hypothesis that excess levels of dietary phytanic acid are responsible for both the overexpression of AMACR in prostate cancer and the potential association between PCa risk and intake of dairy foods and red meat.
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Yachana
authors.initials: Y
authors.lastname: Kataria
authors.forename: Margaret
authors.initials: M
authors.lastname: Wright
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Deaton
authors.forename: Erika Enk
authors.initials: EE
authors.lastname: Rueter
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Rybicki
authors.forename: Ann B
authors.initials: AB
authors.lastname: Moser
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Ananthanrayanan
authors.forename: Peter H
authors.initials: PH
authors.lastname: Gann
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003611:Dairy Products / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D010831:Phytanic Acid / Q000378:metabolism*; D011468:Prostatectomy / Q000639:trends; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019998:Racemases and Epimerases / Q000096:biosynthesis*; D014018:Tissue Distribution / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D010831:Phytanic Acid; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase
keywords: AMACR; biomarker; diet; phytanic acid; prostate cancer