Utility of incorporating genetic variants for the early detection of prostate cancer.
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.
Nam
Robert K
RK
Division of Urology, Sunnybrook Research Institute, Department of Radiation Oncology, Sunnybrook Health Sciences, University of Toronto, Toronto, Ontario, Canada. Robert.nam@utoronto.ca
Zhang
William W
WW
Trachtenberg
John
J
Seth
Arun
A
Klotz
Laurence H
LH
Stanimirovic
Aleksandra
A
Punnen
Sanoj
S
Venkateswaran
Vasundara
V
Toi
Ants
A
Loblaw
D Andrew
DA
Sugar
Linda
L
Siminovitch
Katherine A
KA
Narod
Steven A
SA
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
D005819:Genetic Markers; D017430:Prostate-Specific Antigen