dc.contributor.author | Kerin, Michael J. | |
dc.contributor.author | Miller, Nicola | |
dc.date.accessioned | 2013-12-02T15:35:20Z | |
dc.date.available | 2013-12-02T15:35:20Z | |
dc.date.issued | 2013-04 | |
dc.identifier.citation | Bojesen, S. E., Pooley, K. A., Johnatty, S. E., Beesley, J., Michailidou, K., Tyrer, J. P., et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet, 45(4), 371-384. | en_US |
dc.identifier.issn | 1546-1718 | |
dc.identifier.uri | http://hdl.handle.net/10379/3883 | |
dc.description | Journal article | en_US |
dc.description.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. | en_US |
dc.description.sponsorship | European Commission Seventh Framework Programme (agreement 223175-HEALTH-F2-2009-223175); Cancer Research UK (C1287/A10118 and C1287/A12014) | en_US |
dc.format | application/pdf | en_US |
dc.language.iso | en | en_US |
dc.publisher | Nature Publishing Group (Macmillan) | en_US |
dc.relation.ispartof | Nature Genetics | en |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | Genetics | en_US |
dc.subject | Breast cancer susceptibility | en_US |
dc.title | Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. | en_US |
dc.type | Article | en_US |
dc.date.updated | 2013-07-03T11:30:39Z | |
dc.identifier.doi | 10.1038/ng.2566 | |
dc.local.publishedsource | http://dx.doi.org/10.1038/ng.2566 | en_US |
dc.description.peer-reviewed | peer-reviewed | |
dc.contributor.funder | |~| | |
dc.internal.rssid | 3829133 | |
dc.local.contact | Michael Kerin, Dept. Of Surgery, Clinical Science Institute, Nui Galway. 87-4203 Email: michael.kerin@nuigalway.ie | |
dc.local.copyrightchecked | No | |
dc.local.version | PUBLISHED | |
nui.item.downloads | 656 | |