KLK3 and Familial prostate cancer: Although serum-based PSA screening is widely used, PSA has the following limitations as an early detection biomarker [20]–[23]: (i) Elevated levels of serum PSA have been observed not only in prostate cancer, but also in benign prostatic hyperplasia patients, therefore PSA is not specific to prostate cancer, and (ii) PSA is not sufficiently sensitive as indicated by the Prostate Cancer Prevention Trial (PCPT), which demonstrated that 15% of men with PSA levels of 4 ng/ml had prostate cancer and 15% of these patients had high Gleason grade disease.