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About this Publication
Title
Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression.
Pubmed ID
23535824 (View this publication on the PubMed website)
Publication
Hum. Mol. Genet. 2013 Jun; Volume 22 (Issue 12): Pages 2520-8
Authors

Kote-Jarai Z, Saunders EJ, Leongamornlert DA, Tymrakiewicz M, Dadaev T, Jugurnauth-Little S, Ross-Adams H, Al Olama AA, Benlloch S, Halim S, Russell R, Russel R, Dunning AM, Luccarini C, Dennis J, Neal DE, Hamdy FC, Donovan JL, Muir K, Giles GG, Severi G, Wiklund F, Gronberg H, Haiman CA, Schumacher F, Henderson BE, Le Marchand L, Lindstrom S, Kraft P, Hunter DJ, Gapstur S, Chanock S, Berndt SI, Albanes D, Andriole G, Schleutker J, Weischer M, Canzian F, Riboli E, Key TJ, Travis RC, Campa D, Ingles SA, John EM, Hayes RB, Pharoah P, Khaw KT, Stanford JL, Ostrander EA, Signorello LB, Thibodeau SN, Schaid D, Maier C, Vogel W, Kibel AS, Cybulski C, Lubinski J, Cannon-Albright L, Brenner H, Park JY, Kaneva R, Batra J, Spurdle A, Clements JA, Teixeira MR, Govindasami K, Guy M, Wilkinson RA, Sawyer EJ, Morgan A, Dicks E, Baynes C, Conroy D, Bojesen SE, Kaaks R, Vincent D, Bacot F, Tessier DC, COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative, UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology, UK ProtecT Study Collaborators, PRACTICAL Consortium, Easton DF, Eeles RA

Abstract

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.

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