In men with prostate cancer, the adrenal-restrictive HSD3B1(1245A) allele limits conversion from DHEA to potent androgens, whereas the adrenal-permissive HSD3B1(1245C) allele harbors a 367T missense that stabilizes the enzyme, enables potent androgen synthesis, and leads to more rapid development of resistance to androgen deprivation therapy and next-generation hormonal therapies, thus shortening overall survival (19, 20, 21, 22, 23, 24, 25). The gene discussed is HSD3B1; the disease is Familial prostate cancer.