KLK3 and Familial prostate cancer: Over the past 2 decades, prostate cancer patients have become the largest cancer population among all cancer patients in the United States and European Union countries.1 Together with prostate specific antigen (PSA), digital rectal examination (DRE) had been recommended as the preferred method for prostate cancer screening over the past decades.2,3 But the performance of DRE in detecting prostate abnormalities varies greatly and the agreement between examiners is low.4 Moreover, DRE can lead to rectal discomfort, rectal bleeding and even syncope,4 an alternative approach for DRE is needed.5,6