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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2019

01-05-2019 | Prostate Cancer | Original Article

The impact of genetic polymorphism on CYP19A1 in androgen-deprivation therapy among Japanese men

Authors: Masaki Shiota, Naohiro Fujimoto, Shigehiro Tsukahara, Miho Ushijima, Ario Takeuchi, Eiji Kashiwagi, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Masatoshi Eto

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2019

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Abstract

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.
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Metadata
Title
The impact of genetic polymorphism on CYP19A1 in androgen-deprivation therapy among Japanese men
Authors
Masaki Shiota
Naohiro Fujimoto
Shigehiro Tsukahara
Miho Ushijima
Ario Takeuchi
Eiji Kashiwagi
Junichi Inokuchi
Katsunori Tatsugami
Takeshi Uchiumi
Masatoshi Eto
Publication date
01-05-2019
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-019-03811-8

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