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Title: Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
Author(s): Bojesen, S.E.; Pooley, K.A.; Johnatty, S.E.; Beesley, J.; Michailidou, K.; Tyrer, J.P.; Edwards, S.L.; Pickett, H.A.; Shen, H.C.; Smart, C.E.; Hillman, K.M.; Mai, P.L.; Lawrenson, K.; Stutz, M.D.; Lu, Y.; Karevan, R.; Woods, N.; Johnston, R.L.; French, J.D.; Chen, X.; Weischer, M.; Nielsen, S.F.; Maranian, M.J.; Ghoussaini, M.; Ahmed, S.; Baynes, C.; Bolla, M.K.; Wang, Q.; Dennis, J.; McGuffog, L.; Barrowdale, D.; Lee, A.; Healey, S.; Lush, M.; Tessier, D.C.; Vincent, D.; Bacot, F.; Vergote, I.; Lambrechts, S.; Despierre, E.; Risch, H.A.; Gonzalez-Neira, A.; Rossing, M.A.; Pita, G.; Doherty, J.A.; Alvarez, N.; Larson, M.C.; Fridley, B.L.; Schoof, N.; Chang-Claude, J.; Cicek, M.S.; Peto, J.; Kalli, K.R.; Broeks, A.; Armasu, S.M.; Schmidt, M.K.; Braaf, L.M.; Winterhoff, B.; Nevanlinna, H.; Konecny, G.E.; Lambrechts, D.; Rogmann, L.; Guenel, P.; Teoman, A.; Milne, R.L.; Garcia, J.J.; Cox, A; Shridhar, V.; Burwinkel, B.; Marme, F.; Hein, R.; Sawyer, E.J.; Haiman, C.A.; Wang-Gohrke, S.; Andrulis, I.L.; Moysich, K.B.; Hopper, J.L.; Odunsi, K.; Lindblom, A.; Giles, G.G.; Brenner, H.; Simard, J.; Lurie, G.; Fasching, P.A.; Carney, M.E.; Radice, P.; Wilkens, L.R.; Swerdlow, A.; Goodman, M.T.; Kiemeney, L.A.L.M. ; Aben, K.K.H. ; Altena, A.M. van ; Massuger, L.F.A.G. ; Mensenkamp, A.R. ; et al.
Publication year: 2013
Source: Nature Genetics, vol. 45, iss. 4, (2013), pp. 371-384
ISSN: 1061-4036
Related links: http://www.ncbi.nlm.nih.gov/pubmed/23535731
DOI: https://doi.org/10.1038/ng.2566
Publication type: Article / Letter to editor

Please use this identifier to cite or link to this item : http://hdl.handle.net/2066/118827   http://hdl.handle.net/2066/118827

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Subject: NCEBP 1: Molecular epidemiology ONCOL 5: Aetiology, screening and detection
ONCOL 1: Hereditary cancer and cancer-related syndromes
ONCOL 3: Translational research
ONCOL 3: Translational research IGMD 3: Genomic disorders and inherited multi-system disorders
ONCOL 5: Aetiology, screening and detection NCMLS 2: Immune Regulation
ONCOL 3: Translational research IGMD 3: Genomic disorders and inherited multi-system disorders
Organization: Health Evidence
Urology
Gynaecology
Human Genetics
Former Organization: Epidemiology, Biostatistics & HTA
Journal title:
Nature Genetics
Volume: vol. 45
Issue: iss. 4
Page start: p. 371
Page end: p. 384
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 approximately 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.

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