The androgen receptor (AR) and estrogen receptor (ER) play key roles as transcriptional factor in prostate development and carcinogenesis. Identification of androgen- and estrogen-regulated genes is essential to elucidate the pathophysiology of AR and ER in prostate cancer (PCa). Therefore, we propose that single-nucleotide polymorphisms (SNPs) located at AR and ER binding sites are likely to affect the expression of the AR and ER target genes, and may contribute to the susceptibility of human PCa, the prognosis after radical prostatectomy (RP) (the standard initial therapy for localized PCa), and the prognosis after androgen deprivation therapy (ADT) (the standard initial therapy for locally advanced or metastatic PCa). The objectives of this proposed project are: 1) To perform a genome-wide analysis of AR and ER binding sites. 2) To identify SNPs located on the AR and ER binding sites in the genome-wide scale. 3) To comprehensively evaluate the association of each SNP on AR and ER binding sites with the risk of PCa and prognosis after RP and ADT in the population studies. 4) To investigate the potential functional significance of the SNPs, nearby AR/ER target genes, and their association with PCa susceptibility. 5) Finally, to correlate candidate gene expression with PCa progression using tissue microarray. This proposed study is unique and novel because we aim to discover potential prognostic markers and susceptibility gene variants for PCa via a whole genome AR/ER binding site association design. In addition, findings from this study will be particularly noteworthy and help us understand the etiology of the PCa.
