@article{e92c89dbecc34f7aabc4a84b0d688b11,
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.",
author = "Bojesen, {Stig E} and Pooley, {Karen A} and Johnatty, {Sharon E} and Jonathan Beesley and Kyriaki Michailidou and Tyrer, {Jonathan P} and Edwards, {Stacey L} and Pickett, {Hilda A} and Shen, {Howard C} and Smart, {Chanel E} and Hillman, {Kristine M} and Mai, {Phuong L} and Kate Lawrenson and Stutz, {Michael D} and Yi Lu and Rod Karevan and Nicholas Woods and Johnston, {Rebecca L} and French, {Juliet D} and Xiaoqing Chen and Maren Weischer and Nielsen, {Sune F} and Maranian, {Melanie J} and Maya Ghoussaini and Shahana Ahmed and Caroline Baynes and Bolla, {Manjeet K} and Qin Wang and Joe Dennis and Lesley McGuffog and Daniel Barrowdale and Lee, {Andrew Roger} and Sue Healey and Michael Lush and Tessier, {Daniel C} and Daniel Vincent and Fran{\c c}is Bacot and Ignace Vergote and Sandrina Lambrechts and Evelyn Despierre and Kjaer, {Susanne Kr{\"u}ger} and Allan Jensen and Estrid H{\o}gdall and Nordestgaard, {B{\o}rge G} and Henrik Flyger and Engelholm, {Svend Aage} and H{\o}gdall, {Claus K} and Hansen, {Thomas V O} and Anne-Marie Gerdes and Bent Ejlertsen and {Australian Cancer Study}",
year = "2013",
month = apr,
doi = "10.1038/ng.2566",
language = "English",
volume = "45",
pages = "371--84, 384e1--2",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "4",
}