Oxford University Press (OUP), Human Molecular Genetics, 20(22), p. 4239-4239
DOI: 10.1093/hmg/ddt334
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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. ; Kote-Jarai, Zsofia Saunders, Edward J Leongamornlert, Daniel A Tymrakiewicz, Malgorzata Dadaev, Tokhir Jugurnauth-Little, Sarah Ross-Adams, Helen Al Olama, Ali Amin Benlloch, Sara Halim, Silvia Russel, Roslin Dunning, Alison M Luccarini, Craig Dennis, Joe Neal, David E Hamdy, Freddie C Donovan, Jenny L Muir, Ken Giles, Graham G Severi, Gianluca Wiklund, Fredrik Gronberg, Henrik Haiman, Christopher A Schumacher, Fredrick Henderson, Brian E Marchand, Loic Le Lindstrom, Sara Kraft, Peter Hunter, David J Gapstur, Susan Chanock, Stephen Berndt, Sonja I Albanes, Demetrius Andriole, Gerald Schleutker, Johanna Weischer, Maren Canzian, Federico Riboli, Elio Key, Tim J Travis, Ruth C Campa, Daniele Ingles, Sue A John, Esther M Hayes, Richard B Pharoah, Paul Khaw, Kay-Tee Stanford, Janet L Ostrander, Elaine A Signorello, Lisa B Thibodeau, Stephen N Schaid, Dan Maier, Christiane Vogel, Walther Kibel, Adam S Cybulski, Cezary Lubinski, Jan Cannon-Albright, Lisa Brenner, Hermann Park, Jong Y Kaneva, Radka Batra, Jyotsna Spurdle, Amanda Clements, Judith A Teixeira, Manuel R Govindasami, Koveela Guy, Michelle Wilkinson, Rosemary A Sawyer, Emma J Morgan, Angela Dicks, Ed Baynes, Caroline Conroy, Don Bojesen, Stig E Kaaks, Rudolf Vincent, Daniel Bacot, Francois Tessier, Daniel C COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative The UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology The UK ProtecT Study Collaborators The PRACTICAL Consortium Easton, Douglas F Eeles, Rosalind A Human molecular genetics Hum Mol Genet. 2013 Mar 27.