Association of fatty-acid synthase polymorphisms and expression with outcomes after radical prostatectomy

J. Cheng, R. P. Ondracek, D. C. Mehedint, K. A. Kasza, B. Xu, S. Gill, G. Azabdaftari, S. Yao, C. D. Morrison, J. L. Mohler, J. R. Marshall

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)182-189
Number of pages8
JournalProstate Cancer and Prostatic Diseases
Volume18
Issue number2
DOIs
StatePublished - Jun 14 2015
Externally publishedYes

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Fatty Acid Synthases
Prostatectomy
Single Nucleotide Polymorphism
Staining and Labeling
Androgens
Prostatic Neoplasms
Gene Expression
Proteins
Treatment Failure
Prostate
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

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Association of fatty-acid synthase polymorphisms and expression with outcomes after radical prostatectomy. / Cheng, J.; Ondracek, R. P.; Mehedint, D. C.; Kasza, K. A.; Xu, B.; Gill, S.; Azabdaftari, G.; Yao, S.; Morrison, C. D.; Mohler, J. L.; Marshall, J. R.

In: Prostate Cancer and Prostatic Diseases, Vol. 18, No. 2, 14.06.2015, p. 182-189.

Research output: Contribution to journalArticle

Cheng, J, Ondracek, RP, Mehedint, DC, Kasza, KA, Xu, B, Gill, S, Azabdaftari, G, Yao, S, Morrison, CD, Mohler, JL & Marshall, JR 2015, 'Association of fatty-acid synthase polymorphisms and expression with outcomes after radical prostatectomy', Prostate Cancer and Prostatic Diseases, vol. 18, no. 2, pp. 182-189. https://doi.org/10.1038/pcan.2015.11
Cheng, J. ; Ondracek, R. P. ; Mehedint, D. C. ; Kasza, K. A. ; Xu, B. ; Gill, S. ; Azabdaftari, G. ; Yao, S. ; Morrison, C. D. ; Mohler, J. L. ; Marshall, J. R. / Association of fatty-acid synthase polymorphisms and expression with outcomes after radical prostatectomy. In: Prostate Cancer and Prostatic Diseases. 2015 ; Vol. 18, No. 2. pp. 182-189.
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T1 - Association of fatty-acid synthase polymorphisms and expression with outcomes after radical prostatectomy

AU - Cheng, J.

AU - Ondracek, R. P.

AU - Mehedint, D. C.

AU - Kasza, K. A.

AU - Xu, B.

AU - Gill, S.

AU - Azabdaftari, G.

AU - Yao, S.

AU - Morrison, C. D.

AU - Mohler, J. L.

AU - Marshall, J. R.

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Y1 - 2015/6/14

N2 - 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.

AB - 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.

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