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Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

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  • Zsofia Kote-Jarai
  • Edward J Saunders
  • Daniel A Leongamornlert
  • Malgorzata Tymrakiewicz
  • Tokhir Dadaev
  • Sarah Jugurnauth-Little
  • Helen Ross-Adams
  • Ali Amin Al Olama
  • Sara Benlloch
  • Silvia Halim
  • Roslin Russel
  • Alison M Dunning
  • Craig Luccarini
  • Joe Dennis
  • David E Neal
  • Freddie C Hamdy
  • Jenny L Donovan
  • Ken Muir
  • Graham G Giles
  • Gianluca Severi
  • Fredrik Wiklund
  • Henrik Gronberg
  • Christopher A Haiman
  • Fredrick Schumacher
  • Brian E Henderson
  • Loic Le Marchand
  • Sara Lindstrom
  • Peter Kraft
  • David J Hunter
  • Susan Gapstur
  • Stephen Chanock
  • Sonja I Berndt
  • Demetrius Albanes
  • Gerald Andriole
  • Johanna Schleutker
  • Maren Weischer
  • Federico Canzian
  • Elio Riboli
  • Tim J Key
  • Ruth C Travis
  • Daniele Campa
  • Sue A Ingles
  • Esther M John
  • Richard B Hayes
  • Paul Pharoah
  • Kay-Tee Khaw
  • Janet L Stanford
  • Elaine A Ostrander
  • Lisa B Signorello
  • Stig E Bojesen
  • COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative
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Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.
Original languageEnglish
JournalHuman Molecular Genetics
Volume22
Issue number12
Pages (from-to)2520-8
Number of pages9
ISSN0964-6906
DOIs
Publication statusPublished - 15 Jun 2013

ID: 39766137