The University of Southampton
University of Southampton Institutional Repository

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

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
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.
1061-4036
371-384
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Hall, Per
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Monteiro, Alvaro N.A.
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Pharoah, Paul D.P.
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Reddel, Roger R.
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Goode, Ellen L.
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Berchuck, Andrew
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Chenevix-Trench, Georgia
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Bojesen, Stig E., Pooley, Karen A. and Johnatty, Sharon E. et al. (2013) Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nature Genetics, 45 (4), 371-384. (doi:10.1038/ng.2566). (PMID:23535731)

Record type: Article

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.

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More information

Accepted/In Press date: 31 January 2013
e-pub ahead of print date: 27 March 2013
Published date: April 2013
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 383028
URI: https://eprints.soton.ac.uk/id/eprint/383028
ISSN: 1061-4036
PURE UUID: 66e60dec-280f-4b59-8578-ef485879e89c

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Date deposited: 19 Oct 2015 09:20
Last modified: 04 Dec 2017 17:31

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Author: Stig E. Bojesen
Author: Karen A. Pooley
Author: Sharon E. Johnatty
Author: Jonathan Beesley
Author: Kyriaki Michailidou
Author: Jonathan P. Tyrer
Author: Stacey L. Edwards
Author: Hilda A. Pickett
Author: Howard C. Shen
Author: Chanel E. Smart
Author: Kristine M. Hillman
Author: Phuong L. Mai
Author: Kate Lawrenson
Author: Michael D. Stutz
Author: Yi Lu
Author: Rod Karevan
Author: Nicholas Woods
Author: Rebecca L. Johnston
Author: Juliet D. French
Author: Xiaoqing Chen
Author: Maren Weischer
Author: Sune F. Nielsen
Author: Melanie J. Maranian
Author: Maya Ghoussaini
Author: Shahana Ahmed
Author: Caroline Baynes
Author: Manjeet K. Bolla
Author: Qin Wang
Author: Joe Dennis
Author: Lesley McGuffog
Author: Daniel Barrowdale
Author: Andrew Lee
Author: Sue Healey
Author: Michael Lush
Author: Daniel C. Tessier
Author: Daniel Vincent
Author: Françis Bacot
Author: Ignace Vergote
Author: Sandrina Lambrechts
Author: Evelyn Despierre
Author: Harvey A. Risch
Author: Anna González-Neira
Author: Mary Anne Rossing
Author: Guillermo Pita
Author: Jennifer A. Doherty
Author: Nuria Álvarez
Author: Melissa C. Larson
Author: Brooke L. Fridley
Author: Nils Schoof
Author: Jenny Chang-Claude
Author: Mine S. Cicek
Author: Julian Peto
Author: Kimberly R. Kalli
Author: Annegien Broeks
Author: Sebastian M. Armasu
Author: Marjanka K. Schmidt
Author: Linde M. Braaf
Author: Boris Winterhoff
Author: Heli Nevanlinna
Author: Gottfried E. Konecny
Author: Diether Lambrechts
Author: Lisa Rogmann
Author: Pascal Guénel
Author: Attila Teoman
Author: Roger L. Milne
Author: Joaquin J. Garcia
Author: Angela Cox
Author: Vijayalakshmi Shridhar
Author: Barbara Burwinkel
Author: Frederik Marme
Author: Rebecca Hein
Author: Elinor J. Sawyer
Author: Christopher A. Haiman
Author: Shan Wang-Gohrke
Author: Irene L. Andrulis
Author: Kirsten B. Moysich
Author: John L. Hopper
Author: Kunle Odunsi
Author: Annika Lindblom
Author: Graham G. Giles
Author: Hermann Brenner
Author: Jacques Simard
Author: Galina Lurie
Author: Peter A. Fasching
Author: Michael E. Carney
Author: Paolo Radice
Author: Lynne R. Wilkens
Author: Anthony Swerdlow
Author: Marc T. Goodman
Author: Hiltrud Brauch
Author: Montserrat Garcia-Closas
Author: Peter Hillemanns
Author: Robert Winqvist
Author: Matthias Dürst
Author: Peter Devilee
Author: Ingo Runnebaum
Author: Anna Jakubowska
Author: Jan Lubinski
Author: Arto Mannermaa
Author: Ralf Butzow
Author: Natalia V Bogdanova
Author: Thilo Dörk
Author: Liisa M. Pelttari
Author: Wei Zheng
Author: Arto Leminen
Author: Hoda Anton-Culver
Author: Clareann H. Bunker
Author: Vessela Kristensen
Author: Roberta B Ness
Author: Kenneth Muir
Author: Robert Edwards
Author: Alfons Meindl
Author: Florian Heitz
Author: Keitaro Matsuo
Author: Andreas du Bois
Author: Anna H Wu
Author: Philipp Harter
Author: Soo-Hwang Teo
Author: Ira Schwaab
Author: Xiao-Ou Shu
Author: William Blot
Author: Satoyo Hosono
Author: Daehee Kang
Author: Toru Nakanishi
Author: Mikael Hartman
Author: Yasushi Yatabe
Author: Ute Hamann
Author: Beth Y Karlan
Author: Suleeporn Sangrajrang
Author: Susanne Krüger Kjaer
Author: Valerie Gaborieau
Author: Allan Jensen
Author: Diana Eccles
Author: Estrid Høgdall
Author: Chen-Yang Shen
Author: Judith Brown
Author: Yin Ling Woo
Author: Mitul Shah
Author: Mat Adenan Noor Azmi
Author: Robert Luben
Author: Siti Zawiah Omar
Author: Kamila Czene
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