Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression.
Kote-Jarai, Zsofia 1,*; Saunders, Edward J. 1,+; Leongamornlert, Daniel A. 1,+; Tymrakiewicz, Malgorzata 1,+; Dadaev, Tokhir 1,+; Jugurnauth-Little, Sarah 1,+; Ross-Adams, Helen 2; Al Olama, Ali Amin 3; Benlloch, Sara 3; Halim, Silvia 2; Russel, Roslin 2; Dunning, Alison M. 3; Luccarini, Craig 3; Dennis, Joe 3; Neal, David E. 4,5,++; Hamdy, Freddie C. 6,7,++; Donovan, Jenny L. 8,++; Muir, Ken 9,++; Giles, Graham G. 10,11,++; Severi, Gianluca 10,11,++; Wiklund, Fredrik 12,++; Gronberg, Henrik 12,++; Haiman, Christopher A. 13,++; Schumacher, Fredrick 13,++; Henderson, Brian E. 13,++; Le Marchand, Loic 14,++; Lindstrom, Sara 15,++; Kraft, Peter 15,++; Hunter, David J. 15,++; Gapstur, Susan 16,++; Chanock, Stephen 17,++; Berndt, Sonja I. 17,++; Albanes, Demetrius 18,++; Andriole, Gerald 19,++; Schleutker, Johanna 20,21,++; Weischer, Maren 22,++; Canzian, Federico 23,++; Riboli, Elio 24,++; Key, Tim J. 25,++; Travis, Ruth C. 26,27,++; Campa, Daniele 20,21,++; Ingles, Sue A. 13,++; John, Esther M. 26,27,++; Hayes, Richard B. 28,++; Pharoah, Paul 3,++; Khaw, Kay-Tee 29,++; Stanford, Janet L. 30,31,++; Ostrander, Elaine A. 32,++; Signorello, Lisa B. 33,34,++; Thibodeau, Stephen N. 35,++; Schaid, Dan 35,++; Maier, Christiane 36,++; Vogel, Walther 36,++; Kibel, Adam S. 37,++; Cybulski, Cezary 38,++; Lubinski, Jan 38,++; Cannon-Albright, Lisa 39,40,++; Brenner, Hermann 41,++; Park, Jong Y. 42,++; Kaneva, Radka 43,++; Batra, Jyotsna 44,45,++; Spurdle, Amanda 46,++; Clements, Judith A. 44,45,++; Teixeira, Manuel R. 47,48,++; Govindasami, Koveela 1; Guy, Michelle 1; Wilkinson, Rosemary A. 1; Sawyer, Emma J. 1; Morgan, Angela 1; Dicks, Ed 3; Baynes, Caroline 3; Conroy, Don 3; Bojesen, Stig E. 22; Kaaks, Rudolf 23; Vincent, Daniel 49; Bacot, Francois 49; Tessier, Daniel C. 49; COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative [P]; The UK Genetic Prostate Cancer Study CollaboratorsBritish Association of Urological Surgeons' Section of Oncology /[S]; The UK ProtecT Study Collaborators [S]; The PRACTICAL Consortium [S]; Easton, Douglas F. 3; Eeles, Rosalind A. 1
[Article]
Human Molecular Genetics.
22(12):2520-2528, June 15, 2013.
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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.
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