Please use this identifier to cite or link to this item:
https://hdl.handle.net/2445/126080
Title: | Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer |
Author: | Blanco Guillermo, Ignacio Australian Cancer Study Australian Ovarian Cancer Study Group GENICA (Gene Environment Interaction and Breast Cancer) SWE-BRCA Group HEBON Investigators EMBRACE Collaborators GEMO Study Collaborators |
Keywords: | Càncer d'ovari Càncer de mama Telòmer Ovarian cancer Breast cancer Telomere |
Issue Date: | 27-Mar-2013 |
Publisher: | Nature Publishing Group |
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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1038/ng.2566 |
It is part of: | Nature Genetics, 2013, vol. 45, num. 4, p. 371-384 |
URI: | https://hdl.handle.net/2445/126080 |
Related resource: | https://doi.org/10.1038/ng.2566 |
ISSN: | 1061-4036 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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