A functional polymorphism in the CYR61 (IGFBP10) gene is associated with prostate cancer risk.

ABSTRACT

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.