Genetic predisposition to early recurrence in clinically localized prostate cancer
Por:
Borque, A, del Amo, J, Esteban, LM, Ars, E, Hernandez, C, Planas, J, Arruza, A, Llarena, R, Palou, J, Herranz, F, Raventos, CX, Tejedor, D, Artieda, M, Simon, L, Martinez, A, Carceller, E, Suarez, M, Allue, M, Sanz, G, Morote, J
Publicada:
1 abr 2013
Resumen:
Objectives
To evaluate genetic susceptibility to early biochemical recurrence (EBCR) after radical prostatectomy (RP), as a prognostic factor for early systemic dissemination.
To build a preoperative nomogram to predict EBCR combining genetic and clinicopathological factors.
Patients and Methods
We evaluated 670 patients from six University Hospitals who underwent RP for clinically localized prostate cancer (PCa), and were followed-up for at least 5 years or until biochemical recurrence.
EBCR was defined as a level prostate-specific antigen >0.4 ng/mL within 1 year of RP; preoperative variables studied were: age, prostate-specific antigen, clinical stage, biopsy Gleason score, and the genotype of 83 PCa-related single nucleotide polymorphisms (SNPs).
Univariate allele association tests and multivariate logistic regression were used to generate predictive models for EBCR, with clinicopathological factors and adding SNPs.
We internally validated the models by bootstrapping and compared their accuracy using the area under the curve (AUC), net reclassification improvement, integrated discrimination improvement, calibration plots and Vickers' decision curves.
Results
Four common SNPs at KLK3, KLK2, SULT1A1 and BGLAP genes were independently associated with EBCR.
A significant increase in AUC was observed when SNPs were added to the model: AUC (95% confidence interval) 0.728 (0.674-0.784) vs 0.763 (0.708-0.817).
Net reclassification improvement showed a significant increase in probability for events of 60.7% and a decrease for non-events of 63.5%.
Integrated discrimination improvement and decision curves confirmed the superiority of the new model.
Conclusions
Four SNPs associated with EBCR significantly improved the accuracy of clinicopathological factors.
We present a nomogram for preoperative prediction of EBCR after RP.
Filiaciones:
Borque, A:
Miguel Servet Univ Hosp, Zaragoza 50009, Spain
del Amo, J:
Progenika Biopharma SA, Bilbao, Spain
Esteban, LM:
Univ Zaragoza, Zaragoza, Spain
Ars, E:
Puigvert Fdn, Barcelona, Spain
Hernandez, C:
Gregorio Maranon Univ Hosp, Madrid, Spain
Planas, J:
Vall dHebron Univ Hosp, Barcelona, Spain
Arruza, A:
Hosp Txagorritxu, Vitoria, Spain
Llarena, R:
Univ Hosp Cruces, Bilbao, Spain
Palou, J:
Puigvert Fdn, Barcelona, Spain
Herranz, F:
Gregorio Maranon Univ Hosp, Madrid, Spain
Raventos, CX:
Vall dHebron Univ Hosp, Barcelona, Spain
Tejedor, D:
Progenika Biopharma SA, Bilbao, Spain
Artieda, M:
Progenika Biopharma SA, Bilbao, Spain
Simon, L:
Progenika Biopharma SA, Bilbao, Spain
Martinez, A:
Progenika Biopharma SA, Bilbao, Spain
Carceller, E:
Miguel Servet Univ Hosp, Zaragoza 50009, Spain
Suarez, M:
Miguel Servet Univ Hosp, Zaragoza 50009, Spain
Allue, M:
Vall dHebron Univ Hosp, Barcelona, Spain
Sanz, G:
Univ Zaragoza, Zaragoza, Spain
Morote, J:
Vall dHebron Univ Hosp, Barcelona, Spain
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