Purpose: Inadequate suppression of testosterone during androgen-deprivation therapy impairs its efficacy. This study investigated the significance of genetic polymorphism in CYP19A1, which encodes aromatase that catalyzes androgens into estrogens, among men treated with primary ADT for metastatic prostate cancer.
Methods: This study included 80 Japanese patients with metastatic prostate cancer whose serum testosterone levels during ADT were available. The association of CYP19A1 gene polymorphism (rs1870050) with clinicopathological parameters including serum testosterone levels during ADT as well as progression-free survival and overall survival was examined.
Results: Serum testosterone levels during ADT of men carrying homozygous wild-type (AA) in the CYP19A1 gene [median (interquartile range); 11.6 (8.3-20.3) ng/dl] were higher than those in men carrying the heterozygous/homozygous variant (AC/CC) [median (interquartile range); 10.0 (6.4-12.8) ng/dl]. When adjusted by Gleason score, initial PSA, M-stage and serum testosterone level during ADT, heterozygous/homozygous variant (AC/CC) in the CYP19A1 gene was associated with a lower risk of progression to castration resistance [hazard ratio (95% confidence interval), 0.53 [0.29-0.92], p = 0.025], but not to any-cause death [hazard ratio (95% confidence interval), 0.74 [0.36-1.49], p = 0.40].
Conclusions: These findings suggest that genetic variation in CYP19A1 (rs1870050) might affect the prognosis of patients with metastatic prostate cancer when treated with ADT by regulating serum testosterone levels.
Keywords: Androgen-deprivation therapy; Aromatase; CYP19A1; Prostate cancer; Testosterone.