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

SE Bojesen; KA Pooley; SE Johnatty; J Beesley; K Michailidou; JP Tyrer; SL Edwards; HA Pickett; HC Shen; CE Smart; KM Hillman; PL Mai; K Lawrenson; MD Stutz; Y Lu; R Karevan; N Woods; RL Johnston; JD French; X Chen; M Weischer; SF Nielsen; MJ Maranian; M Ghoussaini; S Ahmed; C Baynes; MK Bolla; Q Wang; J Dennis; L McGuffog; D Barrowdale; A Lee; S Healey; M Lush; DC Tessier; D Vincent; F Bacot; I Vergote; S Lambrechts; E Despierre; HA Risch; A González-Neira; MA Rossing; G Pita; JA Doherty; N Álvarez; MC Larson; BL Fridley; N Schoof; J Chang-Claude; MS Cicek; J Peto; KR Kalli; A Broeks; SM Armasu; MK Schmidt; LM Braaf; B Winterhoff; H Nevanlinna; GE Konecny; D Lambrechts; L Rogmann; P Guénel; A Teoman; RL Milne; JJ Garcia; A Cox; V Shridhar; B Burwinkel; F Marme; R Hein; EJ Sawyer; CA Haiman; S Wang-Gohrke; IL Andrulis; KB Moysich; JL Hopper; K Odunsi; A Lindblom; GG Giles; H Brenner; J Simard; G Lurie; PA Fasching; ME Carney; P Radice; LR Wilkens; A Swerdlow; MT Goodman; H Brauch; M Garcia-Closas; P Hillemanns; R Winqvist; M Dürst; P Devilee; I Runnebaum; A Jakubowska; J Lubinski; A Mannermaa; R Butzow

Journal article

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

SE Bojesen, KA Pooley, SE Johnatty, J Beesley, K Michailidou, JP Tyrer, SL Edwards, HA Pickett, HC Shen, CE Smart, KM Hillman, PL Mai, K Lawrenson, MD Stutz, Y Lu, R Karevan, N Woods, RL Johnston, JD French, X Chen Show all

Nature Genetics | NATURE PUBLISHING GROUP | Published : 2013

DOI: 10.1038/ng.2566

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. ..

View full abstract

University of Melbourne Researchers

Roger Milne Author

Graham Giles Author

Melissa Southey Author

Riccardo Dolcetti Author

Grants

Awarded by National Institutes of Health

Funding Acknowledgements

We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. COGS is funded through a grant from the European Commission's Seventh Framework Programme (agreement 223175 HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK (C1287/A10118 and C1287/Al2014). BCAC meetings have been funded by the European Union Cooperation in Science and Technology (COST) programme (BM0606). Telomere length measurement and analysis were funded by Cancer Research UK project grant C1287/A9540 and Chief Physician Johan Boserup and Lise Boserup's Fund. CIMBA data management and analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. OCAC is supported by a grant from the Ovarian Cancer Research Fund thanks to the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program (J.S. and D.E.) and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701; J.S., D.E. and P. Hall). Scientific development and funding of the OCAC portion of this project were supported by Genetic Associations and Mechanisms in Oncology (GAME-ON; U19-CA148112). CIMBA genotyping was supported by US National Institutes of Health (NIH) grant CAl28978, a National Cancer Institute (NCI) Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a US Department of Defense Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. This study made use of data generated by The Wellcome Trust Case Control Consortium (funding was provided by Wellcome Trust award 076113) and the TCGA Pilot Project established by NCI and the National Human Genome Research Institute.