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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.
Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
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;Vergote, Ignace;Lambrechts, Sandrina;Despierre, Evelyn;Risch, Harvey A.;González Neira, Anna;Rossing, Mary Anne;Pita, Guillermo;Doherty, Jennifer A.;Álvarez, 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;Winqvist, Robert;Dürst, Matthias;Devilee, Peter;Runnebaum, Ingo;Jakubowska, Anna;Lubinski, Jan;Mannermaa, Arto;Butzow, Ralf;Bogdanova, Natalia V.;Dörk, Thilo;Pelttari, Liisa M.;Zheng, Wei;Leminen, Arto;Anton Culver, Hoda;Bunker, Clareann H.;Kristensen, Vessela;Ness, Roberta B.;Muir, Kenneth;Edwards, Robert;Meindl, Alfons;Heitz, Florian;Matsuo, Keitaro;Du Bois, Andreas;Wu, Anna H.;Harter, Philipp;Teo, Soo Hwang;Schwaab, Ira;Shu, Xiao Ou;Blot, William;Hosono, Satoyo;Kang, Daehee;Nakanishi, Toru;Hartman, Mikael;Yatabe, Yasushi;Hamann, Ute;Karlan, Beth Y.;Sangrajrang, Suleeporn;Kjaer, Susanne Krüger;Gaborieau, Valerie;Jensen, Allan;Eccles, Diana;Høgdall, Estrid;Shen, Chen Yang;Brown, Judith;Woo, Yin Ling;Shah, Mitul;Azmi, Mat Adenan Noor;Luben, Robert;Omar, Siti Zawiah;Czene, Kamila;Vierkant, Robert A.;Nordestgaard, Børge G.;Flyger, Henrik;Vachon, Celine;Olson, Janet E.;Wang, Xianshu;Levine, Douglas A.;Rudolph, Anja;Weber, Rachel Palmieri;Flesch Janys, Dieter;Iversen, Edwin;Nickels, Stefan;Schildkraut, Joellen M.;Silva, Isabel Dos Santos;Cramer, Daniel W.;Gibson, Lorna;Terry, Kathryn L.;Fletcher, Olivia;Vitonis, Allison F.;Van Der Schoot, C. Ellen;Poole, Elizabeth M.;Hogervorst, Frans B. L.;Tworoger, Shelley S.;Liu, Jianjun;Bandera, Elisa V.;Li, Jingmei;Olson, Sara H.;Humphreys, Keith;Orlow, Irene;Blomqvist, Carl;Rodriguez Rodriguez, Lorna;Aittomäki, Kristiina;Salvesen, Helga B.;Muranen, Taru A.;Wik, Elisabeth;Brouwers, Barbara;Krakstad, Camilla;Wauters, Els;Halle, Mari K.;Wildiers, Hans;Kiemeney, Lambertus A.;Mulot, Claire;Aben, Katja K.;Laurent Puig, Pierre;Altena, Anne Mvan;Truong, Thérèse;Massuger, Leon F. A. G.;Benitez, Javier;Pejovic, Tanja;Perez, Jose Ignacio Arias;Hoatlin, Maureen;Zamora, M. Pilar;Cook, Linda S.;Balasubramanian, Sabapathy P.;Kelemen, Linda E.;Schneeweiss, Andreas;Le, Nhu D.;Sohn, Christof;Brooks Wilson, Angela;Tomlinson, Ian;Kerin, Michael J.;Miller, Nicola;Cybulski, Cezary;Henderson, Brian E.;Menkiszak, Janusz;Schumacher, Fredrick;Wentzensen, Nicolas;Le Marchand, Loic;Yang, Hannah P.;Mulligan, Anna Marie;Glendon, Gord;Engelholm, Svend Aage;Knight, Julia A.;Høgdall, Claus K.;Apicella, Carmel;Gore, Martin;Tsimiklis, Helen;Song, Honglin;Southey, Melissa C.;Jager, Agnes;Den Ouweland, Ans M. Wvan;Brown, Robert;Martens, John W. M.;Flanagan, James M.;Kriege, Mieke;Paul, James;Margolin, Sara;Siddiqui, Nadeem;Severi, Gianluca;Whittemore, Alice S.;BAGLIETTO, LAURA;Mcguire, Valerie;Stegmaier, Christa;Sieh, Weiva;Müller, Heiko;Arndt, Volker;Labrèche, France;Gao, Yu Tang;Goldberg, Mark S.;Yang, Gong;Dumont, Martine;Mclaughlin, John R.;Hartmann, Arndt;Ekici, Arif B.;Beckmann, Matthias W.;Phelan, Catherine M.;Lux, Michael P.;Permuth Wey, Jenny;Peissel, Bernard;Sellers, Thomas A.;Ficarazzi, Filomena;Barile, Monica;Ziogas, Argyrios;Ashworth, Alan;Gentry Maharaj, Aleksandra;Jones, Michael;Ramus, Susan J.;Orr, Nick;Menon, Usha;Pearce, Celeste L.;Brüning, Thomas;Pike, Malcolm C.;Ko, Yon Dschun;Lissowska, Jolanta;Figueroa, Jonine;Kupryjanczyk, Jolanta;Chanock, Stephen J.;Dansonka Mieszkowska, Agnieszka;Jukkola Vuorinen, Arja;Rzepecka, Iwona K.;Pylkäs, Katri;Bidzinski, Mariusz;Kauppila, Saila;Hollestelle, Antoinette;Seynaeve, Caroline;Tollenaar, Rob A. E. M.;Durda, Katarzyna;Jaworska, Katarzyna;Hartikainen, Jaana M.;Kosma, Veli Matti;Kataja, Vesa;Antonenkova, Natalia N.;Long, Jirong;Shrubsole, Martha;Deming Halverson, Sandra;Lophatananon, Artitaya;Siriwanarangsan, Pornthep;Stewart Brown, Sarah;Ditsch, Nina;Lichtner, Peter;Schmutzler, Rita K.;Ito, Hidemi;Iwata, Hiroji;Tajima, Kazuo;Tseng, Chiu Chen;Stram, Daniel O.;Van Den Berg, David;Yip, Cheng Har;Ikram, M. Kamran;Teh, Yew Ching;Cai, Hui;Lu, Wei;Signorello, Lisa B.;Cai, Qiuyin;Noh, Dong Young;Yoo, Keun Young;Miao, Hui;Iau, Philip Tsau Choong;Teo, Yik Ying;Mckay, James;Shapiro, Charles;Ademuyiwa, Foluso;Fountzilas, George;Hsiung, Chia Ni;Yu, Jyh Cherng;Hou, Ming Feng;Healey, Catherine S.;Luccarini, Craig;Peock, Susan;Stoppa Lyonnet, Dominique;Peterlongo, Paolo;Rebbeck, Timothy R.;Piedmonte, Marion;Singer, Christian F.;Friedman, Eitan;Thomassen, Mads;Offit, Kenneth;Hansen, Thomas V. O.;Neuhausen, Susan L.;Szabo, Csilla I.;Blanco, Ignacio;Garber, Judy;Narod, Steven A.;Weitzel, Jeffrey N.;Montagna, Marco;Olah, Edith;Godwin, Andrew K.;Yannoukakos, Drakoulis;Goldgar, David E.;Caldes, Trinidad;Imyanitov, Evgeny N.;Tihomirova, Laima;Arun, Banu K.;Campbell, Ian;Mensenkamp, Arjen R.;Van Asperen, Christi J.;Van Roozendaal, Kees E. P.;Meijers Heijboer, Hanne;Collée, J. Margriet;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, Åke;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.
2013-01-01
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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/817872
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.