title: Chromatin interactions and candidate genes at ten prostate cancer risk loci.
abstract: Genome-wide association studies have identified more than 100 common single nucleotide polymorphisms (SNPs) that are associated with prostate cancer risk. However, the vast majority of these SNPs lie in noncoding regions of the genome. To test whether these risk SNPs regulate their target genes through long-range chromatin interactions, we applied capture-based 3C sequencing technology to investigate possible cis-interactions at ten prostate cancer risk loci in six cell lines. We identified significant physical interactions between risk regions and their potential target genes including CAPG at 2p11.2, C2orf43 at 2p24.1, RFX6 at 6q22.1, NFASC at 1q32.1, MYC at 8q24.1 and AGAP7P at 10q11.23. Most of the interaction peaks were co-localized to regions of active histone modification and transcription factor binding sites. Expression quantitative trait locus (eQTL) analysis showed suggestive eQTL signals at rs1446669, rs699664 and rs1078004 for CAPG (p < 0.004), rs13394027 for C2orf43 (p = 2.25E-27), rs10993994 and rs4631830 for AGAP7P (p < 8.02E-5). Further analysis revealed an enhancer activity at genomic region surrounding rs4631830 which was expected to disrupt HOXB-like DNA binding affinity. This study identifies a set of candidate genes and their potential regulatory variants, and provides additional evidence showing the role of long-range chromatin interactions in prostate cancer etiology.
authors.affiliation: Department of Pathology, MCW Cancer Center, Medical College of Wisconsin, Milwaukee, 53226, WI, USA.
authors.forename: Meijun
authors.initials: M
authors.lastname: Du
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, 55905, MN, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Tillmans
authors.affiliation: Beijing 3H Medical Technology Co. Ltd., Beijing, 100176, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Gao
authors.affiliation: Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Pathology, MCW Cancer Center, Medical College of Wisconsin, Milwaukee, 53226, WI, USA.
authors.forename: Tiezheng
authors.initials: T
authors.lastname: Yuan
authors.affiliation: Department of Pathology, MCW Cancer Center, Medical College of Wisconsin, Milwaukee, 53226, WI, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Dittmar
authors.affiliation: Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Biostatistics, Institute for Health &Society, Medical College of Wisconsin, Milwaukee, 53226, WI, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Sahr
authors.affiliation: Division of Biostatistics, Institute for Health &Society, Medical College of Wisconsin, Milwaukee, 53226, WI, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Gong-Hong
authors.initials: GH
authors.lastname: Wei
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, 55905, MN, USA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.affiliation: Department of Pathology, MCW Cancer Center, Medical College of Wisconsin, Milwaukee, 53226, WI, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics*; D044127:Epigenesis, Genetic; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D058977:Molecular Sequence Annotation; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D012306:Risk; D017422:Sequence Analysis, DNA
chemical_list: D002843:Chromatin