title: Gene expression and biological pathways in tissue of men with prostate cancer in a randomized clinical trial of lycopene and fish oil supplementation.
abstract: BACKGROUND
  Studies suggest that micronutrients may modify the risk or delay progression of prostate cancer; however, the molecular mechanisms involved are poorly understood. We examined the effects of lycopene and fish oil on prostate gene expression in a double-blind placebo-controlled randomized clinical trial.
  
  
  METHODS
  Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-month intervention of lycopene (n = 29) or fish oil (n = 27) supplementation or placebo (n = 28). Gene expression in morphologically normal prostate tissue was studied at baseline and at 3 months via cDNA microarray analysis. Differential gene expression and pathway analyses were performed to identify genes and pathways modulated by these micronutrients.
  
  
  RESULTS
  Global gene expression analysis revealed no significant individual genes that were associated with high intake of fish or tomato at baseline or after 3 months of supplementation with lycopene or fish oil. However, exploratory pathway analyses of rank-ordered genes (based on p-values not corrected for multiple comparisons) revealed the modulation of androgen and estrogen metabolism in men who routinely consumed more fish (p = 0.029) and tomato (p = 0.008) compared to men who ate less. In addition, modulation of arachidonic acid metabolism (p = 0.01) was observed after 3 months of fish oil supplementation compared with the placebo group; and modulation of nuclear factor (erythroid derived-2) factor 2 or Nrf2-mediated oxidative stress response for either supplement versus placebo (fish oil: p = 0.01, lycopene: p = 0.001).
  
  
  CONCLUSIONS
  We did not detect significant individual genes associated with dietary intake and supplementation of lycopene and fish oil. However, exploratory analyses revealed candidate in vivo pathways that may be modulated by these micronutrients.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00402285.
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Mark Jesus M
authors.initials: MJ
authors.lastname: Magbanua
authors.forename: Ritu
authors.initials: R
authors.lastname: Roy
authors.forename: Eduardo V
authors.initials: EV
authors.lastname: Sosa
authors.forename: Vivian
authors.initials: V
authors.lastname: Weinberg
authors.forename: Scott
authors.initials: S
authors.lastname: Federman
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mattie
authors.forename: Millie
authors.initials: M
authors.lastname: Hughes-Fulford
authors.forename: Jeff
authors.initials: J
authors.lastname: Simko
authors.forename: Katsuto
authors.initials: K
authors.lastname: Shinohara
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Haqq
authors.forename: Peter R
authors.initials: PR
authors.lastname: Carroll
authors.forename: June M
authors.initials: JM
authors.lastname: Chan
mesh_terms: D002338:Carotenoids / Q000494:pharmacology* / Q000627:therapeutic use; D004032:Diet; D019587:Dietary Supplements; D004311:Double-Blind Method; D005395:Fish Oils / Q000494:pharmacology* / Q000627:therapeutic use; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000077276:Lycopene; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010919:Placebos; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*
chemical_list: D005395:Fish Oils; D010919:Placebos; D002338:Carotenoids; D000077276:Lycopene