Association of Fatty Acid Synthase Polymorphisms and Expression with Prostate Cancer Recurrence after Radical Prostatectomy
Jinrong Cheng, Rochelle D Payne Ondracek, Karin A Kasza, Bo Xu, James R Marshall. Roswell Park Cancer Institute, Buffalo, NY
Background: Fatty acid synthase (FAS), selectively overexpressed in prostate cancer cells, may contribute to the aggressiveness of prostate cancer (PCA). Constitutional genetic variation of the FAS gene and the expression levels of FAS protein in tumor cells could be a predictor for outcomes after radical prostatectomy (RP). This study evaluates the associations of single nucleotide polymorphisms (SNPs) and the expression of the FAS gene with post-prostatectomy prostate cancer recurrence.
Design: Seven tagging SNPs that represent the entire set of FAS gene SNPs were genotyped in 643 Caucasian men who had RP at our institute from 1993 to 2005. FAS protein expression was assessed by IHC staining. Treatment outcome was evaluated by a range of end points, including post treatment PSA > 0.2 ng/ml, PSA doubling time < 6 months, NCCN failure, AUA failure, metastatic PCA and PCA-specific mortality. Cox proportional hazards analyses were used to evaluate the associations between each tagging SNP and each endpoint. Bivariate associations with outcomes were considered for each tagging SNP and the associations were controlled for well-established risk factors, including age at surgery, body mass index (BMI), pathologic stage and pathologic grade. The associations of FAS protein staining with each tagging SNP and each endpoint are currently under investigation.
Results: FAS SNPs were generally not associated with the clinical and pathological risk factors. The minor variant T allele of SNP rs4246444 was associated with higher risk of at least 1 detectable PSA (adjusted HR=1.27, P=0.042), at least 2 detectable PSAs (adjusted HR=1.4, P=0.011) and AUA failure (adjusted HR=1.42, P=0.036). The minor variant A allele of SNP rs1127678 was associated with decreased risk of NCCN failure (adjusted HR=0.72, P=0.052) and marginally associated with decreased metastasis risk after RP (adjusted HR=0.43, P=0.081).
Conclusions: Our results suggest that FAS genetic variation may be a new independent predictor of the recurrence of PCA after RP.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 79, Tuesday Morning