Monday, May 21, 2012 1:00 PM-3:00 PM
Prostate Cancer: Detection and Screening I
Supported in part by the Urological Research foundation, Prostate SPORE grant (P50 CA90386-05S2) and the Robert H. Lurie Comprehensive cancer Center grant (P30 CA60553)
1209: PERSONALIZED PSA TESTING USING GENETIC VARIANTS CAN POSSIBLY DECREASE THE NUMBER OF PROSTATE BIOPSIES
Brian T. Helfand
Matthias D. Hofer
Dae Y. Kim
Phillip R. Cooper
Barry B. McGuire
William J. Catalona
Introduction and Objectives
PSA testing has limited performance characteristics for the diagnosis of prostate cancer (CaP). A promising possibility to improve PSA testing is to integrate a patient’s genetic information. Recent studies have identified 4 genetic variants associated with increased PSA levels (Sci Trans Med 2010. 2(62):62). The increase risk of being diagnosed with CaP conferred by these variants may be mediated principally through their effects on increasing serum PSA levels. By correcting for the effects of these variants on PSA, it may be possible to create a personalized PSA cutoff that can better inform the decision to recommend a prostate biopsy. We therefore determined how many men would continue to meet common biopsy criteria after genetic PSA correction.
The genotypes of 4 genetic variants associated with PSA levels (rs2736098, rs10788160, rs11067228, and rs17632542) were determined for 964 Caucasian healthy volunteers from 2003-2011. PSA values adjusted for genotype were calculated and weighted by dividing PSA values by their combined genetic risk, as previously described (Sci Trans Med). Statistical analyses were used to compare the percentage of men who would meet commonly-used PSA thresholds (>2.5 or 4.0ng/ml).
As an example, we determined the adjusted PSA for hypothetical men with genotypes for a variable number of PSA genetic variants (ranging from 0-4) and a PSA of 2.5ng/ml (Table 1). As demonstrated, the genetic PSA correction is weighted so that the adjusted PSA value decreases with the number of PSA variants carried. Significantly fewer men would be recommended to have a prostate biopsy after genetic adjustment(Table 2). For example, using 2.5 or 4.0 ng/ml as the biopsy threshold, genetic PSA correction would lead to a 15% and 20% relative reduction in potentially unnecessary biopsies, respectively.
Our results suggest that a personalized PSA value can be obtained by adjusting for the presence of 4 genetic variants that influence PSA levels. These values can be used to prevent unnecessary biopsies and improve the clinical performance characteristics of PSA.