title: Impact of DNA repair gene polymorphisms on the risk of biochemical recurrence after radiotherapy and overall survival in prostate cancer.
abstract: 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.
authors.affiliation: Experimental and Clinical Pharmacology Unit, National Cancer Institute, Aviano, PN, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Zanusso
authors.affiliation: Department of Radiation Oncology, National Cancer Institute, Aviano, PN, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bortolus
authors.affiliation: Experimental and Clinical Pharmacology Unit, National Cancer Institute, Aviano, PN, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Dreussi
authors.affiliation: Epidemiology and Biostatistics Unit, National Cancer Institute, Aviano, PN, Italy.
authors.forename: Jerry
authors.initials: J
authors.lastname: Polesel
authors.affiliation: Experimental and Clinical Pharmacology Unit, National Cancer Institute, Aviano, PN, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Montico
authors.affiliation: Experimental and Clinical Pharmacology Unit, National Cancer Institute, Aviano, PN, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Cecchin
authors.affiliation: Experimental and Clinical Pharmacology Unit, National Cancer Institute, Aviano, PN, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gagno
authors.affiliation: Experimental and Clinical Pharmacology Unit, National Cancer Institute, Aviano, PN, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Rizzolio
authors.affiliation: Department of Radiation Oncology, National Cancer Institute, Aviano, PN, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Arcicasa
authors.affiliation: Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Novara
authors.affiliation: Experimental and Clinical Pharmacology Unit, National Cancer Institute, Aviano, PN, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004260:DNA Repair; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D016019:Survival Analysis
keywords: DNA repair; biochemical recurrence; overall survival; polymorphisms; prostate cancer