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A functional polymorphism in the CYR61 (IGFBP10) gene is associated with prostate cancer risk
1State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Background:
CYR61 (cysteine-rich protein 61, also named IGFBP10) is a secreted signaling molecule that promotes angiogenesis and tumor growth. The goal of this study is to determine whether a functional polymorphism in the promoter region of the CYR61 gene (rs3753793) is associated with prostate cancer (PCa) risk and gene expression in Chinese patients.
Methods:
A total of 665 patients diagnosed with PCa and 703 cancer-free controls were genotyped in this hospital-based case-control study, and 26 PCa tissue samples were evaluated for mRNA expression of CYR61 by real-time quantitative reverse-transcription PCR.
Results:
Men carrying the G allele of rs3753793 (TG+GG) had significantly lower risk of PCa when compared with the TT genotype (odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.61-0.95). The association was generally more pronounced among subgroups of PCa patients with advanced stage (OR = 0.70, 95% CI = 0.53-0.94), Gleason score >7 (OR = 0.63, 95% CI = 0.46-0.86) and PSA>20 ng ml(-1) (OR = 0.68, 95% CI = 0.53-0.88). Prostate tumors derived from cases with the GT/GG genotypes had significantly lower levels of CYR61 mRNA when compared with cases with the TT genotypes (P = 0.02).
Conclusions:
Our results indicate that the genetic variation of rs3753793 in the CYR61 promoter may contribute to genetic predisposition to PCa and intra-tumor expression gene expression.
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