A genetic polymorphism of the osteoprotegerin gene is associated with an increased risk of advanced prostate cancer.
BACKGROUND
The purpose of this study was to evaluate the role of osteoprotegerin gene (OPG) polymorphisms as genetic modifiers in the etiology of prostate cancer (PCa) and disease progression.


METHODS
Three hundred and sixty one patients with PCa and 195 normal controls were enrolled in the study, and two genetic polymorphisms, 149 T/C and 950 T/C in the putative promoter region of OPG, were genotyped.


RESULTS
There was no significant difference in the genotype frequencies between PCa patients and controls (P = 0.939 and 0.294 for 149 T/C and 950 T/C polymorphisms, respectively). However, those patients with TC and TT genotypes in the 950 T/C polymorphism had a significantly increased risk of extraprostatic (age-adjusted odds ratio; aOR = 1.74 and 2.03 for TC and TT genotypes compared with the CC genotype, P = 0.028) and metastatic disease (aOR = 1.72 and 2.76 for TC and TT genotypes compared with the CC genotype, P = 0.009) compared with those with the CC genotype. In addition, analysis of the metastatic PCa patients (Stage D) showed that the presence of the T allele of the OPG 950 T/C polymorphism was an independent risk factor predicting survival by Cox proportional hazard regression analyses (P = 0.031).


CONCLUSIONS
Progression of PCa may be influenced by an intrinsic genetic factor of the host's bone metabolism. The variant C allele of 950 T/C in the OPG promoter may play a major role as a genetic safe guard against progression in patients with PCa.
Narita
Naofumi
N
Department of Urology, Akita University School of Medicine, 1-1-1 Hondo Akita, 010-8543, Japan. narita@doc.med.akita-u.ac.jp
Yuasa
Takeshi
T
Tsuchiya
Norihiko
N
Kumazawa
Teruaki
T
Narita
Shintaro
S
Inoue
Takamitsu
T
Ma
Zhiyong
Z
Saito
Mitsuru
M
Horikawa
Yohei
Y
Satoh
Shigeru
S
Ogawa
Osamu
O
Habuchi
Tomonori
T
D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D053244:Osteoprotegerin / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D012306:Risk
D053244:Osteoprotegerin