TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed approximately 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 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 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 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10(-14)) breast and invasive ovarian (P = 1.3 x 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. ; 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, Francis 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 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