%0 Journal Article
%T A genetic polymorphism of the osteoprotegerin gene is associated with an increased risk of advanced prostate cancer
%A Naofumi Narita
%A Takeshi Yuasa
%A Norihiko Tsuchiya
%A Teruaki Kumazawa
%A Shintaro Narita
%A Takamitsu Inoue
%A Zhiyong Ma
%A Mitsuru Saito
%A Yohei Horikawa
%A Shigeru Satoh
%A Osamu Ogawa
%A Tomonori Habuchi
%J BMC Cancer
%D 2008
%I BioMed Central
%R 10.1186/1471-2407-8-224
%X 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.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).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.Prostate cancer (PCa) has a very high proclivity for metastasizing to bone, with approximately 90% of men with advanced disease having skeletal lesions [1]. Bone is an abundant repository for immobilized growth factors. When osteoclasts absorb bone by secreting protons and proteases, these growth factors are released and provide fertile ground in which tumor cells can grow. Bone-derived growth factors and adhesive molecules secreted by tumor cells can cause modifications in the development and progression of metastatic cancer growth. Indeed, our recent investigation disclosed that a genetic polymorphism in the insulin-like growth factor I gene (IGF1) is a strong modifier of PCa progression [2]. Thus, genetic factors involved in the int
%U http://www.biomedcentral.com/1471-2407/8/224