title: Utility of incorporating genetic variants for the early detection of prostate cancer.
abstract: OBJECTIVE
  Several single nucleotide polymorphisms (SNP) have been associated with the risk of prostate cancer. The clinical utility of using SNPs in the early detection of prostate cancer has not been evaluated.
  
  
  METHODS
  We examined a panel of 25 SNPs from candidate genes and chromosomal regions in 3,004 unselected men who were screened for prostate cancer using serum prostate-specific antigen (PSA) and digital rectal examination. All underwent a prostate biopsy. We evaluated the ability of these SNPs to help predict the presence of prostate cancer at biopsy.
  
  
  RESULTS
  Of the 3,004 patients, 1,389 (46.2%) were found to have prostate cancer. Fifteen of the 25 SNPs studied were significantly associated with prostate cancer (P=0.02-7x10(-8)). We selected a combination of 4 SNPs with the best predictive value for further study. After adjusting for other predictive factors, the odds ratio for patients with all four of the variant genotypes compared with men with no variant genotype was 5.1 (95% confidence interval, 1.6-16.5; P=0.006). When incorporated into a nomogram, genotype status contributed more significantly than PSA, family history, ethnicity, urinary symptoms, and digital rectal examination (area under the curve=0.74). The positive predictive value of the PSA test ranged from 42% to 94% depending on the number of variant genotypes carried (P=1x10(-15)).
  
  
  CONCLUSIONS
  SNP genotyping can be used in a clinical setting for the early detection of prostate cancer in a nomogram approach and by improving the positive predictive value of the PSA test.
authors.affiliation: Division of Urology, Sunnybrook Research Institute, Department of Radiation Oncology, Sunnybrook Health Sciences, University of Toronto, Toronto, Ontario, Canada. Robert.nam@utoronto.ca
authors.forename: Robert K
authors.initials: RK
authors.lastname: Nam
authors.forename: William W
authors.initials: WW
authors.lastname: Zhang
authors.forename: John
authors.initials: J
authors.lastname: Trachtenberg
authors.forename: Arun
authors.initials: A
authors.lastname: Seth
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Klotz
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stanimirovic
authors.forename: Sanoj
authors.initials: S
authors.lastname: Punnen
authors.forename: Vasundara
authors.initials: V
authors.lastname: Venkateswaran
authors.forename: Ants
authors.initials: A
authors.lastname: Toi
authors.forename: D Andrew
authors.initials: DA
authors.lastname: Loblaw
authors.forename: Linda
authors.initials: L
authors.lastname: Sugar
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Siminovitch
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001706:Biopsy; D016022:Case-Control Studies; D042241:Early Diagnosis; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D017430:Prostate-Specific Antigen