The Val158Met polymorphism of the catechol-O-methyltransferase gene is associated with the PSA-progression-free survival in prostate cancer patients treated with estramustine phosphate.
OBJECTIVE
The aim of our study is to find out the good responders for estramustine phosphate (EMP) therapy in patients with prostate cancer. We have focused on the metabolism of EMP and studied the association between a functional single-nucleotide polymorphism in the catechol-O-methyltransferase gene (Val158Met of COMT) and PSA-progression-free survival in Japanese patients with prostate cancer treated by EMP.


METHODS
Seventy-two Japanese patients with previously untreated prostate cancer who were found to be eligible for low-dose EMP therapy were enrolled in the study. Genotyping of the Val158Met polymorphism of COMT was conducted by both the polymerase chain reaction-based restriction fragment length polymorphism method and TaqMan assay.


RESULTS
Patients with the Val/Val genotype of COMT had a significantly higher PSA-progression-free rate as compared to those with the Val/Met or Met/Met genotype (p=0.027). The adjusted hazard ratio of biochemical PSA failure for the Val158Met genotype of COMT was 2.164 (95% CI, 1.111 to 5.525).


CONCLUSIONS
The Val158Met polymorphism of COMT is associated with the PSA-progression-free rate of EMP-treated patients in prostate cancer.
Suzuki
Motofumi
M
Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. suzukim-uro@h.u-tokyo.ac.jp
Mamun
Mohammed Rafiqul Islam
MR
Hara
Kazuo
K
Ozeki
Takeshi
T
Yamada
Yasuhiko
Y
Kadowaki
Takashi
T
Honda
Hidetoshi
H
Yanagihara
Yoshitsugu
Y
Ito
Yoichi Minagawa
YM
Kameyama
Shuji
S
Ohta
Nobutaka
N
Hosoi
Takayuki
T
Arai
Tomio
T
Sawabe
Motoji
M
Takeuchi
Takumi
T
Takahashi
Satoru
S
Kitamura
Tadaichi
T
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D004961:Estramustine / Q000378:metabolism / Q000627:therapeutic use*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011355:Prodrugs / Q000378:metabolism / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics; D014633:Valine / Q000235:genetics
D018931:Antineoplastic Agents, Hormonal; D011355:Prodrugs; D004961:Estramustine; D008715:Methionine; D002394:Catechol O-Methyltransferase; D017430:Prostate-Specific Antigen; D014633:Valine