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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).    Conclusion  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.

A genetic polymorphism of the osteoprotegerin gene is associated with an increased risk of advanced prostate cancer