%0 Journal Article %T Prediagnostic genetic stratification for aggressive prostate cancer¡ªis the puzzle for genetic variants gaining shape? %A Marco Randazzo %A Orlando Burkhardt %J SCIE-indexed Journal %D 2018 %R 10.21037/22661 %X Population-based screening for prostate cancer (PCa) using prostate-specific antigen (PSA) has shown to reduce the cancer-specific mortality but was associated with a high rate of overdiagnosis (1). The reason for this is the high prevalence of PCa (2). Thus, 27 men had to be diagnosed with PCa in order to prevent 1 PCa-specific death in the cited mass screening trial. It is important to recognize, that the mentioned screening study was a population-based trial (= every eligible participant providing consent was tested). There was no risk-stratification intended prior to PSA-testing. A PSA cut-off was the only trigger for biopsy irrespective of risk factors. In addition, conditions increasing the PSA-value such as benign prostate enlargement were not considered in the study protocol. The value of PSA screening is higher among individuals defined by particular characteristics, such as family history of PCa, ethnicity, increasing age, or genetic factors. Therefore, a prediagnostic information on the future risk for aggressive PCa might be of important clinical value in order to stratify individuals at risk. In an attempt to categorize men according to their future risk profile, efforts have been made including baseline PSA-values at younger age (3), family history (4) and single nucleotide polymorphism in the kallikrein 6 region (since PSA is a member of the kallikrein-family) (5) %U http://tcr.amegroups.com/article/view/22661/html