Recent studies have identified genetic variants associated with increased PSA levels and prostate cancer risk, raising the possibility of diagnostic bias. By correcting for these variants, it has been postulated that a “personalized” cut-off for PSA levels could be determined which could help to better stratify patients for prostate biopsy to rule out cancer. Genetic correction of PSA was performed by dividing a subject's PSA value by his combined genetic risk.
Four single nucleotide polymorphisms associated with PSA levels have been identified in healthy subjects without prostate cancer. Genetic correlation of PSA results in 964 Caucasian men was associated with a significantly decreased percentage of men reaching biopsy thresholds, estimating a 15% to 20% relative reduction in biopsies using a threshold of 2.5ng/ml or greater or 4.0ng/ml or greater, respectively. In addition, genetic correlation could results in an 18% to 22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses.
Limitations of this study include a small cohort of only Caucasian men, suggesting the need for a larger study across various ethnicities. The influence of genetic correction on clinical outcomes requires further prospective study in a large, independent cohort. Lastly, the applicability of cost-effectiveness must be considered, since genetic testing may not be readily available across practices.
Reference: Helfand BT, Loeb S, Hu Q, et al. Personalized prostate specific antigen testing using genetic variants may reduce unnecessary prostate biopsies. J Urol 2013;189:1697-1701.