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

研究成果: ジャーナルへの寄稿記事

抄録

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.

元の言語英語
ジャーナルCancer chemotherapy and pharmacology
DOI
出版物ステータス出版済み - 1 1 2019

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Genetic Polymorphisms
Polymorphism
Androgens
Testosterone
Prostatic Neoplasms
Serum
Genes
Hazards
Therapeutics
Confidence Intervals
Aromatase
Neoplasm Grading
Castration
Disease-Free Survival
Cause of Death
Estrogens
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

これを引用

@article{755c4588c71d4ae495211cf167c1af56,
title = "The impact of genetic polymorphism on CYP19A1 in androgen-deprivation therapy among Japanese men",
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.",
author = "masaki shiota and Naohiro Fujimoto and Shigehiro Tsukahara and Miho Ushijima and ario takeuchi and Eiji Kashiwagi and Junichi Inokuchi and Katsunori Tatsugami and Takeshi Uchiumi and Masatoshi Eto",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00280-019-03811-8",
language = "English",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - The impact of genetic polymorphism on CYP19A1 in androgen-deprivation therapy among Japanese men

AU - shiota, masaki

AU - Fujimoto, Naohiro

AU - Tsukahara, Shigehiro

AU - Ushijima, Miho

AU - takeuchi, ario

AU - Kashiwagi, Eiji

AU - Inokuchi, Junichi

AU - Tatsugami, Katsunori

AU - Uchiumi, Takeshi

AU - Eto, Masatoshi

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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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U2 - 10.1007/s00280-019-03811-8

DO - 10.1007/s00280-019-03811-8

M3 - Article

C2 - 30868236

AN - SCOPUS:85063004602

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

ER -