Abstract
PurposeTo investigate the genetic risk score (GRS) from a large-scale exome-wide association study as a tool of prediction for biochemical recurrence (BCR) after radical prostatectomy (RP) in prostate cancer (PCa).ResultsThe 16 SNPs were selected as significant predictors of BCR. The GRS in men experiencing BCR was -1.21, significantly higher than in non-BCR patients (–2.43) (p < 0.001). The 10-year BCR-free survival rate was 46.3% vs. 81.8% in the high-versus low GRS group, respectively (p < 0.001). The GRS was a significant factor after adjusting for other variables in Cox proportional hazard models (HR:1.630, p < 0.001). The predictive ability of the multivariate model without GRS was 84.4%, increased significantly to 88.0% when GRS was included (p = 0.0026).Materials and MethodsTotal 912 PCa patients were enrolled who had received RP and genotype analysis using Exome chip (HumanExome BeadChip). Genetic results were obtained by the methods of logistic regression analysis which measured the odds ratio (OR) to BCR. The GRS was calculated by the sum of each weighted-risk allele count multiplied by the natural logarithm of the respective ORs. Survival analyses were performed using the GRS. We compared the accuracy of separate multivariate models incorporating clinicopathological factors that either included or excluded the GRS.ConclusionsGRS had additional predictive gain of BCR after RP in PCa. The addition of personally calculated GRS significantly increased the BCR prediction rate. After validation of these results, GRS of BCR could be potential biomarker to predict clinical outcomes.
Highlights
Prostate cancer (PCa) is the most common malignant cancer affecting adult males in the United States, it was measured for 15 % of new cancer and 7 % of total male cancer related deaths in 2012 [1]
The 16 single nucleotide polymorphism (SNP) were selected as significant predictors of biochemical recurrence (BCR)
The genetic risk score (GRS) was a significant factor after adjusting for other variables in Cox proportional hazard models (HR:1.630, p < 0.001)
Summary
Prostate cancer (PCa) is the most common malignant cancer affecting adult males in the United States, it was measured for 15 % of new cancer and 7 % of total male cancer related deaths in 2012 [1]. The radical prostatectomy (RP) is the gold standard surgical procedure for localized PCa [2]. Localized PCa had good 10 year biochemical recurrence (BCR) outcomes which reported 73–99%, some. Five years after RP, 15% of men experience this biochemical recurrence (BCR), while 20% to 40% of men exhibit BCR 10 years after RP [5, 6]. Previous reports showed important predictors of BCR were serum prostate specific antigen (PSA), Gleason score, pathological stage such as extracapsular extentsion (ECE) or seminal vesicle invasion (SVI) and positive surgical margins (PSM). Substantial efforts have been www.impactjournals.com/oncotarget made to identify novel prognostic markers such as genetic markers to predict BCR after surgical treatment [3, 7,8,9,10]
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