Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer Journal Article
| Authors: | 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.; González-Neira, A.; Rossing, M. A.; Pita, G.; Doherty, J. A.; Álvarez, 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.; Guénel, 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.; Brauch, H.; Garcia-Closas, M.; Hillemanns, P.; Winqvist, R.; Dürst, M.; Devilee, P.; Runnebaum, I.; Jakubowska, A.; Lubinski, J.; Mannermaa, A.; Butzow, R.; Levine, D. A.; Olson, S. H.; Orlow, I.; Pike, M. C.; Offit, K.; Robson, M. |
| Article Title: | Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer |
| 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. |
| Journal Title: | Nature Genetics |
| Volume: | 45 |
| Issue: | 4 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2013-04-01 |
| Start Page: | 371 |
| End Page: | 384 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 23535731 |
| DOI: | 10.1038/ng.2566 |
| PMCID: | PMC3670748 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):1 - "Export Date: 1 May 2013" - "CODEN: NGENE" - ":doi 10.1038/ng.2566" - "Source: Scopus" |
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