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Oosterwijk Jan C, Hooning Maartje J, Rookus Matti A, van der Luijt Rob B, Os Theo A Mvan, Evans D Gareth, Frost Debra, Fineberg Elena, Barwell Julian, Walker Lisa, Kennedy M John, Platte Radka, Davidson Rosemarie, Ellis Steve D, Cole Trevor, Bressac-de Paillerets Brigitte, Buecher Bruno, Damiola Francesca, Faivre Laurence, Frenay Marc, Sinilnikova Olga M, Caron Olivier, Giraud Sophie, Mazoyer Sylvie, Bonadona Valérie, Caux-Moncoutier Virginie, Toloczko-Grabarek Aleksandra, Gronwald Jacek, Byrski Tomasz, Spurdle Amanda B, Bonanni Bernardo, Zaffaroni Daniela, Giannini Giuseppe, Bernard Loris, Dolcetti Riccardo, Manoukian Siranoush, Arnold Norbert, Engel Christoph, Deissler Helmut, Rhiem Kerstin, Niederacher Dieter, Plendl Hansjoerg, Sutter Christian, Wappenschmidt Barbara, Borg Ake, Melin Beatrice, Rantala Johanna, Soller Maria, Nathanson Katherine L, Domchek Susan M, Rodriguez Gustavo C, Salani Ritu, Kaulich Daphne Gschwantler, Tea Muy-Kheng, Paluch Shani Shimon, Laitman Yael, Skytte Anne-Bine, Kruse Torben A, Jensen Uffe Birk, Robson Mark, Gerdes Anne-Marie, Ejlertsen Bent, Foretova Lenka, Savage Sharon A, Lester Jenny, Soucy Penny, Kuchenbaecker Karoline B, Olswold Curtis, Cunningham Julie M, Slager Susan, Pankratz Vernon S, Dicks Ed, Lakhani Sunil R, Couch Fergus J, Hall Per, Monteiro Alvaro N A, Gayther Simon A, Pharoah Paul D P, Reddel Roger R, Goode Ellen L, Greene Mark H, Easton Douglas F, Berchuck Andrew, Antoniou Antonis C, Chenevix-Trench Georgia, Dunning Alison M
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.
