Impact of DNA repair gene polymorphisms on the risk of biochemical recurrence after radiotherapy and overall survival in prostate cancer
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Chiara Zanusso1, Roberto Bortolus2, Eva Dreussi1, Jerry Polesel3, Marcella Montico1, Erika Cecchin1, Sara Gagno1, Flavio Rizzolio1, Mauro Arcicasa2, Giacomo Novara4, Giuseppe Toffoli1
1Experimental and Clinical Pharmacology Unit, National Cancer Institute, Aviano, PN, Italy
2Department of Radiation Oncology, National Cancer Institute, Aviano, PN, Italy
3Epidemiology and Biostatistics Unit, National Cancer Institute, Aviano, PN, Italy
4Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy
Giuseppe Toffoli, email: [email protected]
Keywords: prostate cancer, polymorphisms, biochemical recurrence, overall survival, DNA repair
Received: October 19, 2016 Accepted: January 27, 2017 Published: February 11, 2017
The identification of biomarkers of biochemical recurrence (BCR) in prostate cancer (PCa) patients undergoing radiotherapy (RT) represents an unanswered clinical issue. The primary aim of this study was the definition of new genetic prognostic biomarkers in DNA repair genes (DRGs), considering both BCR and overall survival (OS) as clinical end-points. The secondary aim was to explore the potential clinical impact of these genetic variants with the decision curve analysis (DCA) and the sensitivity analysis.
We analyzed 22 germline polymorphisms in 14 DRGs on 542 Caucasian PCa patients treated with RT as primary therapy. Significant associations were further tested with a bootstrapping technique. According to our analyses, ERCC2-rs1799793 and EXO1-rs4149963 were significantly associated with BCR (p = 0.01 and p = 0.01, respectively). Moreover, MSH6-rs3136228 was associated with a worse OS (p = 0.04). Nonetheless, the DCA and the sensitivity analyses gave no ultimate response about the clinical impact of such variants.
This study highlights the potential prognostic role of polymorphisms in DRGs for PCa, paving the way to the introduction of not invasive tools for the personalization of patients management. Nonetheless, other prospective studies are necessary to ultimately clarify the clinical impact of pharmacogenetics in PCa.
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