title: A genome-wide survey over the ChIP-on-chip identified androgen receptor-binding genomic regions identifies a novel prostate cancer susceptibility locus at 12q13.13.
abstract: BACKGROUND
  The molecular mechanisms for the genome-wide association studies (GWAS)-identified prostate cancer (PCa) risk-associated single-nucleotide polymorphisms (SNP) remain largely unexplained. One recent finding that the PCa risk SNPs are enriched in genomic regions containing androgen receptor (AR)-binding sites has suggested altered AR signaling as a potentially important mechanism.
  
  
  METHODS
  To explore novel associations by leveraging this knowledge, we utilized a meta-analysis previously done over SNPs harbored in ChIP-on-chip identified AR-binding genomic regions using the GWAS data from the Johns Hopkins Hospital (JHH) and the Cancer Genetic Markers of Susceptibility (CGEMS) study, and subsequently evaluated the top associations in a third population from the CAncer of the Prostate in Sweden (CAPS) study.
  
  
  RESULTS
  One SNP (rs4919743: G>A), located at the KRT8 locus at 12q13.13 which encodes a keratin protein (K8) long used as a prostate epithelial malignancy marker and implicated in the tumorigenesis of several cancer types, was identified to be associated with PCa risk. The frequency of its minor "A" allele was consistently higher in PCa cases than in controls in all three study populations, with a combined OR of 1.22 (95% CI: 1.13-1.32) and an overall P value of 4.50 × 10(-7) (Bonferroni corrected, P = 0.006).
  
  
  CONCLUSIONS
  We have identified a novel genetic locus that is associated with PCa risk.
  
  
  CONCLUSIONS
  This study illustrated the great potential of prior biological knowledge in facilitating the search for novel disease-associated genetic loci. This finding warrants further replication in other studies.
authors.affiliation: Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Junjie
authors.initials: J
authors.lastname: Feng
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Seong-Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Lu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Henrik
authors.initials: H
authors.lastname: Gronberg
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
mesh_terms: D001665:Binding Sites; D002881:Chromosomes, Human, Pair 12; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D023281:Genomics; D005838:Genotype; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism
chemical_list: D011944:Receptors, Androgen