Our study revealed that genetic variation in SGLT2 inhibition targets was linked to a reduced risk of prostate cancer [0.34 (0.23, 0.49), P = 2.21 × 10−8] and PSA [0.26 (0.08, 0.81), P = 2.07 × 10−2]. Here, KLK3 is linked to Familial prostate cancer.