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

Junjie Feng, Jielin Sun, Seong Tae Kim, Yizhen Lu, Zhong Wang, Zheng Zhang, Henrik Gronberg, William B Isaacs, S. Lilly Zheng, Jianfeng Xu

Research output: Contribution to journalArticle

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,weutilized 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). Conclusion: We have identified a novel genetic locus that is associated with PCa risk. Impact: 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.

Original languageEnglish (US)
Pages (from-to)2396-2403
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume20
Issue number11
DOIs
StatePublished - Nov 2011

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Androgen Receptors
Prostatic Neoplasms
Genome
Single Nucleotide Polymorphism
Genetic Loci
Genome-Wide Association Study
Cancer Care Facilities
Genetic Predisposition to Disease
Keratins
Genetic Markers
Sweden
Population
Meta-Analysis
Surveys and Questionnaires
Prostate
Neoplasms
Carcinogenesis
Alleles
Binding Sites
Proteins

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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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. / Feng, Junjie; Sun, Jielin; Kim, Seong Tae; Lu, Yizhen; Wang, Zhong; Zhang, Zheng; Gronberg, Henrik; Isaacs, William B; Zheng, S. Lilly; Xu, Jianfeng.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 20, No. 11, 11.2011, p. 2396-2403.

Research output: Contribution to journalArticle

Feng, Junjie ; Sun, Jielin ; Kim, Seong Tae ; Lu, Yizhen ; Wang, Zhong ; Zhang, Zheng ; Gronberg, Henrik ; Isaacs, William B ; Zheng, S. Lilly ; Xu, Jianfeng. / 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. In: Cancer Epidemiology Biomarkers and Prevention. 2011 ; Vol. 20, No. 11. pp. 2396-2403.
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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,weutilized 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). Conclusion: We have identified a novel genetic locus that is associated with PCa risk. Impact: 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.",
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T1 - 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

AU - Feng, Junjie

AU - Sun, Jielin

AU - Kim, Seong Tae

AU - Lu, Yizhen

AU - Wang, Zhong

AU - Zhang, Zheng

AU - Gronberg, Henrik

AU - Isaacs, William B

AU - Zheng, S. Lilly

AU - Xu, Jianfeng

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N2 - 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,weutilized 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). Conclusion: We have identified a novel genetic locus that is associated with PCa risk. Impact: 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.

AB - 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,weutilized 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). Conclusion: We have identified a novel genetic locus that is associated with PCa risk. Impact: 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.

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