Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.

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 × 1... Mehr ...

Verfasser: Bojesen, Stig E
Pooley, Karen A
Johnatty, Sharon E
Beesley, Jonathan
Michailidou, Kyriaki
Tyrer, Jonathan P
Edwards, Stacey L
Pickett, Hilda A
Shen, Howard C
Smart, Chanel E
Hillman, Kristine M
Mai, Phuong L
Lawrenson, Kate
Stutz, Michael D
Lu, Yi
Karevan, Rod
Woods, Nicholas
Johnston, Rebecca L
French, Juliet D
Chen, Xiaoqing
Weischer, Maren
Nielsen, Sune F
Maranian, Melanie J
Ghoussaini, Maya
Ahmed, Shahana
Baynes, Caroline
Bolla, Manjeet K
Wang, Qin
Dennis, Joe
McGuffog, Lesley
Barrowdale, Daniel
Lee, Andrew
Healey, Sue
Lush, Michael
Tessier, Daniel C
Vincent, Daniel
Bacot, Françis
Australian Cancer Study
Australian Ovarian Cancer Study
Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)
Gene Environment Interaction and Breast Cancer (GENICA)
Swedish Breast Cancer Study (SWE-BRCA)
Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON)
Epidemiological study of BRCA1 & BRCA2 Mutation Carriers (EMBRACE)
Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO)
Vergote, Ignace
Lambrechts, Sandrina
Despierre, Evelyn
Risch, Harvey A
González-Neira, Anna
Rossing, Mary Anne
Pita, Guillermo
Doherty, Jennifer A
Alvarez, Nuria
Larson, Melissa C
Fridley, Brooke L
Schoof, Nils
Chang-Claude, Jenny
Cicek, Mine S
Peto, Julian
Kalli, Kimberly R
Broeks, Annegien
Armasu, Sebastian M
Schmidt, Marjanka K
Braaf, Linde M
Winterhoff, Boris
Nevanlinna, Heli
Konecny, Gottfried E
Lambrechts, Diether
Rogmann, Lisa
Guénel, Pascal
Teoman, Attila
Milne, Roger L
Garcia, Joaquin J
Cox, Angela
Shridhar, Vijayalakshmi
Burwinkel, Barbara
Marme, Frederik
Hein, Rebecca
Sawyer, Elinor J
Haiman, Christopher A
Wang-Gohrke, Shan
Andrulis, Irene L
Moysich, Kirsten B
Hopper, John L
Odunsi, Kunle
Lindblom, Annika
Giles, Graham G
Brenner, Hermann
Simard, Jacques
Lurie, Galina
Fasching, Peter A
Carney, Michael E
Radice, Paolo
Wilkens, Lynne R
Swerdlow, Anthony
Goodman, Marc T
Brauch, Hiltrud
Garcia-Closas, Montserrat
Hillemanns, Peter
Dokumenttyp: Artikel
Erscheinungsdatum: 2013
Reihe/Periodikum: Nature genetics, vol 45, iss 4
Verlag/Hrsg.: eScholarship
University of California
Schlagwörter: Australian Cancer Study / Australian Ovarian Cancer Study / Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer / Gene Environment Interaction and Breast Cancer / Swedish Breast Cancer Study / Hereditary Breast and Ovarian Cancer Research Group Netherlands / Epidemiological study of BRCA1 & BRCA2 Mutation Carriers / Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers / Chromatin / Telomere / Humans / Breast Neoplasms / Ovarian Neoplasms / Genetic Predisposition to Disease / Luciferases / Telomerase / RNA / Messenger / Oligonucleotide Array Sequence Analysis / Risk Factors / Case-Control Studies / Gene Expression Profiling / Reverse Transcriptase Polymerase Chain Reaction / DNA Methylation / Alternative Splicing / Genotype / Polymorphism / Single Nucleotide / Female / Genome-Wide Association Study / Genetic Loci / Real-Time Polymerase Chain Reaction / Biomarkers / Tumor / Genetics / Breast Cancer / Cancer / Ovarian Cancer / Rare Diseases / Prevention / 2.1 Biological and endogenous factors / Aetiology / Biological Sciences / Medical and Health Sciences / Developmental Biology
Sprache: unknown
Permalink: https://search.fid-benelux.de/Record/base-29158532
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://escholarship.org/uc/item/7c505287

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.