title: Association of fatty-acid synthase polymorphisms and expression with outcomes after radical prostatectomy.
abstract: BACKGROUND
  Fatty-acid synthase (FASN), selectively overexpressed in prostate cancer (PCa) cells, has been described as linked to the aggressiveness of PCa. Constitutional genetic variation of the FASN gene and the expression levels of FASN protein in cancer cells could thus be expected to predict outcome after radical prostatectomy (RP). This study evaluates the associations of malignant tissue status, neoadjuvant androgen deprivation therapy (NADT) and single-nucleotide polymorphisms (SNPs) of FASN with FASN protein expression in prostate tissue. The study then examines the associations of FASN SNPs and gene expression with three measures of post-prostatectomy outcome.
  
  
  METHODS
  Seven tagging FASN SNPs were genotyped in 659 European American men who underwent RP at Roswell Park Cancer Institute between 1993 and 2005. FASN protein expression was assessed using immunohistochemistry. The patients were followed for an average of 6.9 years (range: 0.1-20.6 years). Outcome was assessed using three end points: biochemical failure, treatment failure and development of distant metastatic PCa. Cox proportional hazards analyses were used to evaluate the associations of the tagging SNPs and FASN expression with these end points. Bivariate associations with outcomes were considered; the associations also were controlled for known aggressiveness indicators.
  
  
  RESULTS
  Overall, no SNPs were associated with any known aggressiveness indicators. FASN staining intensity was stronger in malignant than in benign tissue, and NADT was associated with decreased FASN staining in both benign and malignant tissue. The relationships of FASN SNPs and staining intensity with outcome were less clear. One SNP, rs4246444, showed a weak association with outcome. FASN staining intensity also showed a weak and seemingly contradictory relationship with outcome.
  
  
  CONCLUSIONS
  Additional study with longer follow-up and populations that include more metastatic patients is warranted.
authors: 1] Department of Cancer Prevention and Population Science, Roswell Park Cancer Institute, Buffalo, NY, USA [2] Department of Pathology, University at Buffalo, Buffalo, NY, USA.
authors: J
authors: J
authors: Cheng
authors: Department of Cancer Prevention and Population Science, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: R P
authors: RP
authors: Ondracek
authors: Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: D C
authors: DC
authors: Mehedint
authors: Department of Cancer Prevention and Population Science, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: K A
authors: KA
authors: Kasza
authors: Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: B
authors: B
authors: Xu
authors: Department of Pathology, University at Buffalo, Buffalo, NY, USA.
authors: S
authors: S
authors: Gill
authors: Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: G
authors: G
authors: Azabdaftari
authors: Department of Cancer Prevention and Population Science, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: S
authors: S
authors: Yao
authors: Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: C D
authors: CD
authors: Morrison
authors: Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: J L
authors: JL
authors: Mohler
authors: Department of Cancer Prevention and Population Science, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: J R
authors: JR
authors: Marshall
mesh_terms: D000368:Aged; D054890:Fatty Acid Synthase, Type I / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D020641:Polymorphism, Single Nucleotide; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I