title: Does genotyping of risk-associated single nucleotide polymorphisms improve patient selection for prostate biopsy when combined with a prostate cancer risk calculator?
abstract: BACKGROUND
  Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with higher risk of prostate cancer (PCa). This study aimed to evaluate whether published SNPs improve the performance of a clinical risk-calculator in predicting prostate biopsy result.
  
  
  METHODS
  Three hundred forty-six patients with a previous prostate biopsy (191 positive, 155 negative) were enrolled. After literature search, nine SNPs were selected for their statistically significant association with increased PCa risk. Allelic odds ratios were computed and a new logistic regression model was built integrating the clinical risk score (i.e., prior biopsy results, PSA level, prostate volume, transrectal ultrasound, and digital rectal examination) and a multilocus genetic risk score (MGRS). Areas under the receiver operating characteristic (ROC) curves (AUC) of the clinical score alone versus the integrated clinic-genetic model were compared. The added value of the MGRS was assessed using the Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) statistics.
  
  
  RESULTS
  Predictive performance of the integrated clinico-genetic model (AUC = 0.781) was slightly higher than predictive performance of the clinical score alone (AUC = 0.770). The prediction of PCa was significantly improved with an IDI of 0.015 (P-value = 0.035) and a continuous NRI of 0.403 (P-value < 0.001).
  
  
  CONCLUSIONS
  The predictive performance of the clinical model was only slightly improved by adding MGRS questioning the real clinical added value with regards to the cost of genetic testing and performance of current inexpensive clinical risk-calculators.
authors.affiliation: Service d'Urologie, Institut de Recherche Expérimentale et Clinique (IREC), Cliniques universitaires Saint Luc, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Valentina
authors.initials: V
authors.lastname: Butoescu
authors.forename: Jérôme
authors.initials: J
authors.lastname: Ambroise
authors.forename: Annabelle
authors.initials: A
authors.lastname: Stainier
authors.forename: Anne-France
authors.initials: AF
authors.lastname: Dekairelle
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Gala
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
mesh_terms: D001706:Biopsy; D051517:Digital Rectal Examination; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D020641:Polymorphism, Single Nucleotide; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D012306:Risk
keywords: genetic; prostate biopsy; prostate-cancer; risk-calculator; single-nucleotide-polymorphisms