Kote-Jarai, Zsofia1; Saunders, Edward J1; Leongamornlert, Daniel A1; Tymrakiewicz, Malgorzata1; Dadaev, Tokhir1; Jugurnauth-Little, Sarah1; Ross-Adams, Helen1; Al Olama, Ali Amin1; Benlloch, Sara1; Halim, Silvia1; Russel, Roslin1; Dunning, Alison M1; Luccarini, Craig1; Dennis, Joe1; Neal, David E1; Hamdy, Freddie C1; Donovan, Jenny L1; Muir, Ken1; Giles, Graham G1; Severi, Gianluca1; Wiklund, Fredrik1; Gronberg, Henrik1; Haiman, Christopher A1; Schumacher, Fredrick1; Henderson, Brian E1; Le Marchand, Loic1; Lindstrom, Sara1; Kraft, Peter1; Hunter, David J1; Gapstur, Susan1; Chanock, Stephen1; Berndt, Sonja I1; Albanes, Demetrius1; Andriole, Gerald1; Schleutker, Johanna1; Weischer, Maren2; Canzian, Federico1; Riboli, Elio1; Key, Tim J1; Travis, Ruth C1; Campa, Daniele1; Ingles, Sue A1; John, Esther M1; Hayes, Richard B1; Pharoah, Paul1; Khaw, Kay-Tee1; Stanford, Janet L1; Ostrander, Elaine A1; Signorello, Lisa B1; Thibodeau, Stephen N1; Schaid, Dan1; Maier, Christiane1; Vogel, Walther1; Kibel, Adam S1; Cybulski, Cezary1; Lubinski, Jan1; Cannon-Albright, Lisa1; Brenner, Hermann1; Park, Sung Jong3; Kaneva, Radka1; Batra, Jyotsna1; Spurdle, Amanda1; Clements, Judith A1; Teixeira, Manuel R1; Govindasami, Koveela1; Guy, Michelle1; Wilkinson, Rosemary A1; Sawyer, Emma J1; Morgan, Angela1; Dicks, Ed1; Baynes, Caroline1; Conroy, Don1; Bojesen, Stig E2; Kaaks, Rudolf1; Vincent, Daniel1; Bacot, François1; Tessier, Daniel C1; Easton, Douglas F1; Eeles, Rosalind A1
1 unknown2 Clinical Biochemistry, Herlev and Gentofte Hospital, The Capital Region of Denmark3 Institut for Fysik og Astronomi
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.
Human Molecular Genetics, 2013, Vol 22, Issue 12, p. 2520-8