Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-04

AUTHORS

Stig E Bojesen, Karen A Pooley, Sharon E Johnatty, Jonathan Beesley, Kyriaki Michailidou, Jonathan P Tyrer, Stacey L Edwards, Hilda A Pickett, Howard C Shen, Chanel E Smart, Kristine M Hillman, Phuong L Mai, Kate Lawrenson, Michael D Stutz, Yi Lu, Rod Karevan, Nicholas Woods, Rebecca L Johnston, Juliet D French, Xiaoqing Chen, Maren Weischer, Sune F Nielsen, Melanie J Maranian, Maya Ghoussaini, Shahana Ahmed, Caroline Baynes, Manjeet K Bolla, Qin Wang, Joe Dennis, Lesley McGuffog, Daniel Barrowdale, Andrew Lee, Sue Healey, Michael Lush, Daniel C Tessier, Daniel Vincent, Françis Bacot, Australian Cancer Study, Australian Ovarian Cancer Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, Gene Environment Interaction and Breast Cancer, Swedish Breast Cancer Study, Breast and Ovarian Cancer Research Group Netherlands, Epidemiological study of BRCA1 & BRCA2 Mutation Carriers, Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers, Ignace Vergote, Sandrina Lambrechts, Evelyn Despierre, Harvey A Risch, Anna González-Neira, Mary Anne Rossing, Guillermo Pita, Jennifer A Doherty, Nuria Álvarez, Melissa C Larson, Brooke L Fridley, Nils Schoof, Jenny Chang-Claude, Mine S Cicek, Julian Peto, Kimberly R Kalli, Annegien Broeks, Sebastian M Armasu, Marjanka K Schmidt, Linde M Braaf, Boris Winterhoff, Heli Nevanlinna, Gottfried E Konecny, Diether Lambrechts, Lisa Rogmann, Pascal Guénel, Attila Teoman, Roger L Milne, Joaquin J Garcia, Angela Cox, Vijayalakshmi Shridhar, Barbara Burwinkel, Frederik Marme, Rebecca Hein, Elinor J Sawyer, Christopher A Haiman, Shan Wang-Gohrke, Irene L Andrulis, Kirsten B Moysich, John L Hopper, Kunle Odunsi, Annika Lindblom, Graham G Giles, Hermann Brenner, Jacques Simard, Galina Lurie, Peter A Fasching, Michael E Carney, Paolo Radice, Lynne R Wilkens, Anthony Swerdlow, Marc T Goodman, Hiltrud Brauch, Montserrat Garcia-Closas, Peter Hillemanns, Robert Winqvist, Matthias Dürst, Peter Devilee, Ingo Runnebaum, Anna Jakubowska, Jan Lubinski, Arto Mannermaa, Ralf Butzow, Natalia V Bogdanova, Thilo Dörk, Liisa M Pelttari, Wei Zheng, Arto Leminen, Hoda Anton-Culver, Clareann H Bunker, Vessela Kristensen, Roberta B Ness, Kenneth Muir, Robert Edwards, Alfons Meindl, Florian Heitz, Keitaro Matsuo, Andreas du Bois, Anna H Wu, Philipp Harter, Soo-Hwang Teo, Ira Schwaab, Xiao-Ou Shu, William Blot, Satoyo Hosono, Daehee Kang, Toru Nakanishi, Mikael Hartman, Yasushi Yatabe, Ute Hamann, Beth Y Karlan, Suleeporn Sangrajrang, Susanne Krüger Kjaer, Valerie Gaborieau, Allan Jensen, Diana Eccles, Estrid Høgdall, Chen-Yang Shen, Judith Brown, Yin Ling Woo, Mitul Shah, Mat Adenan Noor Azmi, Robert Luben, Siti Zawiah Omar, Kamila Czene, Robert A Vierkant, Børge G Nordestgaard, Henrik Flyger, Celine Vachon, Janet E Olson, Xianshu Wang, Douglas A Levine, Anja Rudolph, Rachel Palmieri Weber, Dieter Flesch-Janys, Edwin Iversen, Stefan Nickels, Joellen M Schildkraut, Isabel Dos Santos Silva, Daniel W Cramer, Lorna Gibson, Kathryn L Terry, Olivia Fletcher, Allison F Vitonis, C Ellen van der Schoot, Elizabeth M Poole, Frans B L Hogervorst, Shelley S Tworoger, Jianjun Liu, Elisa V Bandera, Jingmei Li, Sara H Olson, Keith Humphreys, Irene Orlow, Carl Blomqvist, Lorna Rodriguez-Rodriguez, Kristiina Aittomäki, Helga B Salvesen, Taru A Muranen, Elisabeth Wik, Barbara Brouwers, Camilla Krakstad, Els Wauters, Mari K Halle, Hans Wildiers, Lambertus A Kiemeney, Claire Mulot, Katja K Aben, Pierre Laurent-Puig, Anne Mvan Altena, Thérèse Truong, Leon F A G Massuger, Javier Benitez, Tanja Pejovic, Jose Ignacio Arias Perez, Maureen Hoatlin, M Pilar Zamora, Linda S Cook, Sabapathy P Balasubramanian, Linda E Kelemen, Andreas Schneeweiss, Nhu D Le, Christof Sohn, Angela Brooks-Wilson, Ian Tomlinson, Michael J Kerin, Nicola Miller, Cezary Cybulski, Brian E Henderson, Janusz Menkiszak, Fredrick Schumacher, Nicolas Wentzensen, Loic Le Marchand, Hannah P Yang, Anna Marie Mulligan, Gord Glendon, Svend Aage Engelholm, Julia A Knight, Claus K Høgdall, Carmel Apicella, Martin Gore, Helen Tsimiklis, Honglin Song, Melissa C Southey, Agnes Jager, Ans M Wvan den Ouweland, Robert Brown, John W M Martens, James M Flanagan, Mieke Kriege, James Paul, Sara Margolin, Nadeem Siddiqui, Gianluca Severi, Alice S Whittemore, Laura Baglietto, Valerie McGuire, Christa Stegmaier, Weiva Sieh, Heiko Müller, Volker Arndt, France Labrèche, Yu-Tang Gao, Mark S Goldberg, Gong Yang, Martine Dumont, John R McLaughlin, Arndt Hartmann, Arif B Ekici, Matthias W Beckmann, Catherine M Phelan, Michael P Lux, Jenny Permuth-Wey, Bernard Peissel, Thomas A Sellers, Filomena Ficarazzi, Monica Barile, Argyrios Ziogas, Alan Ashworth, Aleksandra Gentry-Maharaj, Michael Jones, Susan J Ramus, Nick Orr, Usha Menon, Celeste L Pearce, Thomas Brüning, Malcolm C Pike, Yon-Dschun Ko, Jolanta Lissowska, Jonine Figueroa, Jolanta Kupryjanczyk, Stephen J Chanock, Agnieszka Dansonka-Mieszkowska, Arja Jukkola-Vuorinen, Iwona K Rzepecka, Katri Pylkäs, Mariusz Bidzinski, Saila Kauppila, Antoinette Hollestelle, Caroline Seynaeve, Rob A E M Tollenaar, Katarzyna Durda, Katarzyna Jaworska, Jaana M Hartikainen, Veli-Matti Kosma, Vesa Kataja, Natalia N Antonenkova, Jirong Long, Martha Shrubsole, Sandra Deming-Halverson, Artitaya Lophatananon, Pornthep Siriwanarangsan, Sarah Stewart-Brown, Nina Ditsch, Peter Lichtner, Rita K Schmutzler, Hidemi Ito, Hiroji Iwata, Kazuo Tajima, Chiu-Chen Tseng, Daniel O Stram, David van den Berg, Cheng Har Yip, M Kamran Ikram, Yew-Ching Teh, Hui Cai, Wei Lu, Lisa B Signorello, Qiuyin Cai, Dong-Young Noh, Keun-Young Yoo, Hui Miao, Philip Tsau-Choong Iau, Yik Ying Teo, James McKay, Charles Shapiro, Foluso Ademuyiwa, George Fountzilas, Chia-Ni Hsiung, Jyh-Cherng Yu, Ming-Feng Hou, Catherine S Healey, Craig Luccarini, Susan Peock, Dominique Stoppa-Lyonnet, Paolo Peterlongo, Timothy R Rebbeck, Marion Piedmonte, Christian F Singer, Eitan Friedman, Mads Thomassen, Kenneth Offit, Thomas V O Hansen, Susan L Neuhausen, Csilla I Szabo, Ignacio Blanco, Judy Garber, Steven A Narod, Jeffrey N Weitzel, Marco Montagna, Edith Olah, Andrew K Godwin, Drakoulis Yannoukakos, David E Goldgar, Trinidad Caldes, Evgeny N Imyanitov, Laima Tihomirova, Banu K Arun, Ian Campbell, Arjen R Mensenkamp, Christi J van Asperen, Kees E P van Roozendaal, Hanne Meijers-Heijboer, J Margriet Collée, Jan C Oosterwijk, Maartje J Hooning, Matti A Rookus, Rob B van der Luijt, Theo A Mvan Os, D Gareth Evans, Debra Frost, Elena Fineberg, Julian Barwell, Lisa Walker, M John Kennedy, Radka Platte, Rosemarie Davidson, Steve D Ellis, Trevor Cole, Brigitte Bressac-de Paillerets, Bruno Buecher, Francesca Damiola, Laurence Faivre, Marc Frenay, Olga M Sinilnikova, Olivier Caron, Sophie Giraud, Sylvie Mazoyer, Valérie Bonadona, Virginie Caux-Moncoutier, Aleksandra Toloczko-Grabarek, Jacek Gronwald, Tomasz Byrski, Amanda B Spurdle, Bernardo Bonanni, Daniela Zaffaroni, Giuseppe Giannini, Loris Bernard, Riccardo Dolcetti, Siranoush Manoukian, Norbert Arnold, Christoph Engel, Helmut Deissler, Kerstin Rhiem, Dieter Niederacher, Hansjoerg Plendl, Christian Sutter, Barbara Wappenschmidt, Åke Borg, Beatrice Melin, Johanna Rantala, Maria Soller, Katherine L Nathanson, Susan M Domchek, Gustavo C Rodriguez, Ritu Salani, Daphne Gschwantler Kaulich, Muy-Kheng Tea, Shani Shimon Paluch, Yael Laitman, Anne-Bine Skytte, Torben A Kruse, Uffe Birk Jensen, Mark Robson, Anne-Marie Gerdes, Bent Ejlertsen, Lenka Foretova, Sharon A Savage, Jenny Lester, Penny Soucy, Karoline B Kuchenbaecker, Curtis Olswold, Julie M Cunningham, Susan Slager, Vernon S Pankratz, Ed Dicks, Sunil R Lakhani, Fergus J Couch, Per Hall, Alvaro N A Monteiro, Simon A Gayther, Paul D P Pharoah, Roger R Reddel, Ellen L Goode, Mark H Greene, Douglas F Easton, Andrew Berchuck, Antonis C Antoniou, Georgia Chenevix-Trench, Alison M Dunning

ABSTRACT

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10(-8)) and BRCA1 mutation carrier (P = 1.1 × 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10(-12)) and BRCA1 mutation carrier (P = 1.6 × 10(-14)) breast and invasive ovarian (P = 1.3 × 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant. More... »

PAGES

371

References to SciGraph publications

Journal

TITLE

Nature Genetics

ISSUE

4

VOLUME

45

Author Affiliations

  • University of Cambridge
  • QIMR Berghofer Medical Research Institute
  • University of Queensland
  • University of Sydney
  • University of Southern California
  • National Cancer Institute
  • Moffitt Cancer Center
  • McGill University and Génome Québec Innovation Centre
  • Universitaire Ziekenhuizen Leuven
  • Yale University
  • Spanish National Cancer Research Centre
  • Fred Hutchinson Cancer Research Center
  • Dartmouth College
  • Mayo Clinic
  • University of Kansas Cancer Center
  • Karolinska Institute
  • German Cancer Research Center
  • London School of Hygiene & Tropical Medicine
  • Antoni van Leeuwenhoek Hospital
  • University of California Los Angeles
  • Flanders Institute for Biotechnology
  • University of Paris-Sud
  • University of Sheffield
  • Heidelberg University
  • University of Cologne
  • King's College London
  • University of Ulm
  • University of Toronto
  • Roswell Park Cancer Institute
  • University of Melbourne
  • Monash University
  • Centre Hospitalier Universitaire de Québec
  • University of Hawaii at Manoa
  • Universitätsklinikum Erlangen
  • Istituto Nazionale dei Tumori
  • Institute of Cancer Research
  • Cedars-Sinai Medical Center
  • University of Tübingen
  • Hannover Medical School
  • University of Oulu
  • Jena University Hospital
  • Leiden University Medical Center
  • Pomeranian Medical University
  • University of Eastern Finland
  • Helsinki University Central Hospital
  • University of California, Irvine
  • University of Pittsburgh
  • University of Oslo
  • The University of Texas Health Science Center at Houston
  • University of Manchester
  • Kliniken Essen-Mitte
  • Aichi Cancer Center
  • University Malaya Medical Centre
  • International Epidemiology Institute
  • Seoul National University
  • Okazaki City Hospital
  • National University of Singapore
  • National Cancer Institute of Thailand
  • Rigshospitalet
  • International Agency For Research On Cancer
  • Danish Cancer Society
  • University of Copenhagen
  • Institute of Biomedical Sciences, Academia Sinica
  • Memorial Sloan Kettering Cancer Center
  • Duke University Hospital
  • University Medical Center Hamburg-Eppendorf
  • Duke University
  • Harvard University
  • Sanquin
  • Brigham and Women's Hospital
  • Genome Institute of Singapore
  • Rutgers University
  • University of Bergen
  • Radboud University Nijmegen Medical Centre
  • French Institute of Health and Medical Research
  • Centre for Biomedical Network Research on Rare Diseases
  • Oregon Health & Science University
  • Hospital Monte Naranco
  • Hospital Universitario La Paz
  • University of New Mexico
  • University of Calgary
  • BC Cancer Agency
  • Simon Fraser University
  • University of Oxford
  • National University of Ireland, Galway
  • University Health Network
  • Lunenfeld-Tanenbaum Research Institute
  • Royal Marsden Hospital
  • Erasmus University Medical Center
  • Imperial College London
  • Beatson West of Scotland Cancer Centre
  • Glasgow Royal Infirmary
  • Cancer Council Victoria
  • Stanford University
  • Krebsregister Saarland
  • University of Montreal
  • Shanghai Cancer Institute
  • Royal Victoria Hospital
  • University of Erlangen-Nuremberg
  • European Institute of Oncology
  • Ruhr University Bochum
  • Centrum Onkologii Instytut
  • Medical University of Warsaw
  • Ministry of Public Health
  • University of Warwick
  • Ludwig Maximilian University of Munich
  • Technical University Munich
  • University Hospital Cologne
  • The Ohio State University
  • Aristotle University of Thessaloniki
  • Tri-Service General Hospital
  • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Paris Descartes University
  • University of Pennsylvania
  • Medical University of Vienna
  • Sheba Medical Center
  • Odense University Hospital
  • City Of Hope National Medical Center
  • University of Delaware
  • Dana–Farber Cancer Institute
  • Istituto Oncologico Veneto
  • National Institute of Oncology
  • University of Kansas Medical Center
  • National Centre of Scientific Research Demokritos
  • University of Utah
  • Hospital Clínico San Carlos
  • Institute of Oncology NN Petrov
  • Latvian Biomedical Research and Study Centre
  • The University of Texas MD Anderson Cancer Center
  • Peter MacCallum Cancer Centre
  • Maastricht University Medical Centre
  • VU University Medical Center
  • University Medical Center Groningen
  • University Medical Center Utrecht
  • Academic Medical Center
  • Manchester University NHS Foundation Trust
  • University Hospitals of Leicester NHS Trust
  • Churchill Hospital
  • St. James's Hospital
  • Southern General Hospital
  • Institut Gustave Roussy
  • Institute Curie
  • Cancer Center of Lyon
  • Centre Georges François Leclerc
  • Centre Antoine Lacassagne
  • Claude Bernard University Lyon 1
  • Sapienza University of Rome
  • Centro di Riferimento Oncologico
  • Kiel University
  • Leipzig University
  • Heinrich Heine University Düsseldorf
  • Lund University
  • Umeå University
  • Karolinska University Hospital
  • Skåne University Hospital
  • NorthShore University HealthSystem
  • Vejle Sygehus
  • Aarhus University Hospital
  • Masaryk Memorial Cancer Institute
  • Royal Brisbane and Women's Hospital
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2566

    DOI

    http://dx.doi.org/10.1038/ng.2566

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1022170805

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23535731


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