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

Author:
  • 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. Johnstonw
  • 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
  • Francis Bacot
  • Ignace Vergote
  • Sandrina Lambrechts
  • Evelyn Despierre
  • Harvey A. Risch
  • Anna Gonzalez-Neira
  • Mary Anne Rossing
  • Guillermo Pita
  • Jennifer A. Doherty
  • Nuria Alvarez
  • 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 Guenel
  • 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 Durst
  • Peter Devilee
  • Ingo Runnebaum
  • Anna Jakubowska
  • Jan Lubinski
  • Arto Mannermaa
  • Ralf Butzow
  • Natalia V. Bogdanova
  • Thilo Doerk
  • 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 Kruger Kjaer
  • Valerie Gaborieau
  • Allan Jensen
  • Diana Eccles
  • Estrid Hogdall
  • Chen-Yang Shen
  • Judith Brown
  • Yin Ling Woo
  • Mitul Shah
  • Mat Adenan Noor Azmi
  • Robert Luben
  • Siti Zawiah Omar
  • Kamila Czene
  • Robert A. Vierkant
  • Borge 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 Row
  • Carl Blomqvist
  • Lorna Rodriguez-Rodriguez
  • Kristiina Aittomaki
  • 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
  • Therese 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. Hogdall
  • 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 Mueller
  • Volker Arndt
  • France Labreche
  • 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 Bruening
  • 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 Pylkas
  • 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 Ikrarn
  • 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 Roozendaa
  • Hanne Meijers-Heijboer
  • J. Margriet Collee
  • 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
  • Valerie 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 Pendl
  • Christian Sutter
  • Barbara Wappenschmidt
  • Åke Borg
  • Beatrice Mein
  • 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 Lesterm
  • 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
Publishing year: 2013
Language: English
Pages: 371-384
Publication/Series: Nature Genetics
Volume: 45
Issue: 4
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 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 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 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 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 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.

Keywords

  • Medical Genetics

Other

Published
  • ISSN: 1546-1718
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90