KLK3 and Familial prostate cancer: Our previous studies have shown that age based PSA increase in men with prostate cancer beyond 69 years could be due to the increase in extra-testicular androgen production from adrenal dehydroepiandrosterone (DHEA)-based androgen precursors [65] catalyzed by the AKR1C3 enzyme, particularly among men carrying the AKR1C3 rs12529 CG and GG genotypes [66].