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Background: Prostate cancer is one of the most commonly diagnosed male malignancies.Genome wide association studies have revealed HNF 1 b to be a major risk gene for prostate cancer susceptibility.The aim of the current study was to provide a preliminary insight into the mechanism of HNF1b in prostate cancer development.Methods: We integrated the data from Gene Expression Omnibus (GEO), prostate cancer genes from Dragon Database of Genes Implicated in Prostate Cancer (DDPC), as well as our previous meta-analysis to generate a panel of genes, which were HNF1b associated prostate cancer risk genes.RT-PCR was applied to assess their expression levels in DU-145, PC3, LNcap, and RWEP-1 cells.Results: 12 genes were found not only associated with HNF1b, but also related to prostate cancer risk.6 of them were mapped in KEGG pathway, and submitted to further gene expression assessment.HNF1b, NR4A1, and HSPD1 were found highly expressed in the LnCap hormone dependent cell line.Compared with the wildtype prostate cancer cells, NR4A1, HSPD 1, ERBB4, and ESR1 expression levels were also found remarkably increased in the HNF1b transfected cells.Conclusions: Our study has implied the mechanism of HNF1b in prostate cancer risk might be associated with modulating the androgenic hormone and prostate cells.Gene to gene interaction and coordination should be taken into account to fully explain the relationships between an interest locus and diseases .