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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