1. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
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Michael Lush, Hans Wildiers, Christopher A. Haiman, Nils Schoof, Per Hall, Beatrice Melin, Hiltrud Brauch, Liisa M. Pelttari, Angela Brooks-Wilson, Laima Tihomirova, Ingo B. Runnebaum, Hui Cai, Kenneth Offit, Michael P. Lux, Robert Edwards, Julia A. Knight, Ignace Vergote, Arto Leminen, Alan Ashworth, Kyriaki Michailidou, Martha J. Shrubsole, Sophie Giraud, Nadeem Siddiqui, Katri Pylkäs, Sune F. Nielsen, Vernon S. Pankratz, Lenka Foretova, Anna González-Neira, Ian Tomlinson, Thérèse Truong, Anna Marie Mulligan, Andreas du Bois, Christi J. van Asperen, Nuria Álvarez, M. Pilar Zamora, Theo A. Mvan Os, Susan J. Ramus, Olivia Fletcher, Usha Menon, Olivier Caron, Dieter Flesch-Janys, Sara H. Olson, Ellen L. Goode, Yael Laitman, Jingmei Li, Lynne R. Wilkens, Carmel Apicella, Brooke L. Fridley, Robert Luben, Mark S. Goldberg, Mary Anne Rossing, Dominique Stoppa-Lyonnet, Jonathan Beesley, Jan Lubinski, Paolo Peterlongo, Phuong L. Mai, Henrik Flyger, Thilo Dörk, Douglas A. Levine, Rob B. van der Luijt, Stig E. Bojesen, Javier Benitez, Natalia Bogdanova, Stephen J. Chanock, Andrew K. Godwin, Sharon E. Johnatty, Helga B. Salvesen, Juliet D. French, Daphne Gschwantler Kaulich, Rod Karevan, Arif B. Ekici, Marc Frenay, Taru A. Muranen, Jirong Long, Catherine S. Healey, Craig Luccarini, Chen-Yang Shen, Lorna Gibson, Pascal Guénel, Hidemi Ito, Nicholas T. Woods, Drakoulis Yannoukakos, Thomas Hansen, Francesca Damiola, Valérie Bonadona, Satoyo Hosono, Marion Piedmonte, Steve Ellis, Suleeporn Sangrajrang, Aleksandra Gentry-Maharaj, James McKay, Olga M. Sinilnikova, Jennifer A. Doherty, Xiao-Ou Shu, Curtis Olswold, Nhu D. Le, Michael J. Kerin, Malcolm C. Pike, Jenny Chang-Claude, Gianluca Severi, Michael Jones, Linda E. Kelemen, Loic Le Marchand, Maureen E. Hoatlin, Fredrick R. Schumacher, Dieter Niederacher, Michael E. Carney, Angela Cox, Attila Teoman, Hannah P. Yang, Graham G. Giles, Jianjun Liu, Xiaoqing Chen, Elisa V. Bandera, Tanja Pejovic, Galina Lurie, Karoline Kuchenbaecker, Mariusz Bidziński, Chanel E. Smart, Maartje J. Hooning, Jose Ignacio Arias Perez, Anne-Marie Gerdes, L. Rogmann, Christoph Engel, Harvey A. Risch, Ignacio Blanco, Isabel dos Santos Silva, Hoda Anton-Culver, Camilla Krakstad, Volker Arndt, Foluso O. Ademuyiwa, Frans B. L. Hogervorst, Stacey L. Edwards, Florian Heitz, Veli-Matti Kosma, Beth Y. Karlan, Robert A. Vierkant, Irene L. Andrulis, Agnieszka Dansonka-Mieszkowska, Hanne Meijers-Heijboer, Alison M. Dunning, Sabapathy P. Balasubramanian, Penny Soucy, Edwin S. Iversen, Heli Nevanlinna, Celeste Leigh Pearce, Melissa C. Southey, Howard C. Shen, Kenneth Muir, Jolanta Lissowska, Clareann H. Bunker, Judy Garber, David Van Den Berg, Yin Ling Woo, Brigitte Bressac-de Paillerets, Rebecca Hein, Norbert Arnold, Saila Kauppila, Lisa Walker, Cezary Cybulski, Estrid Høgdall, Anthony J. Swerdlow, Robert Winqvist, Susanne K. Kjaer, Christa Stegmaier, Kazuo Tajima, Caroline Baynes, Valerie Gaborieau, Keitaro Matsuo, Ed Dicks, Irene Orlow, Torben A Kruse, Rachel Palmieri Weber, David E. Goldgar, Anna Jakubowska, Honglin Song, Antonis C. Antoniou, Paul D.P. Pharoah, Katja K.H. Aben, Lambertus A. Kiemeney, Laurence Faivre, Stefan Nickels, Joellen M. Schildkraut, Yu Tang Gao, Valerie McGuire, Charles L. Shapiro, Sebastian M. Armasu, Katherine L. Nathanson, Marjanka K. Schmidt, Susan L. Neuhausen, Jolanta Kupryjanczyk, Janet E. Olson, Nicolas Wentzensen, Dong Young Noh, Maya Ghoussaini, Ian G. Campbell, Annegien Broeks, Gustavo C. Rodriguez, Rebecca L. Johnston, Shan Wang-Gohrke, Monica Barile, Vesa Kataja, Melanie Maranian, Shahana Ahmed, Christof Sohn, Julie M. Cunningham, Weiva Sieh, Shani Shimon Paluch, Riccardo Dolcetti, John W.M. Martens, Manjeet K. Bolla, Shelley S. Tworoger, Robert S. Brown, Allan Jensen, Hui Miao, Boris Winterhoff, Mari K. Halle, Arndt Hartmann, Loris Bernard, Brian E. Henderson, Els Wauters, Carl Blomqvist, Daniel O. Stram, Karen A. Pooley, Roberta B. Ness, James Paul, Hilda A. Pickett, Wei Zheng, Sandra Deming-Halverson, Soo Hwang Teo, Andrew Lee, Thomas A. Sellers, Philip Iau, D. Gareth Evans, Françis Bacot, Sunil R. Lakhani, Qin Wang, Nick Orr, Celine M. Vachon, Edith Olah, Gong Yang, Svend Aage Engelholm, Martine Dumont, Linda S. Cook, Daniel C. Tessier, Evgeny N. Imyanitov, Paolo Radice, Mikael Hartman, Annika Lindblom, John R. McLaughlin, Radka Platte, Jenny Permuth-Wey, Keun-Young Yoo, Andrew Berchuck, Roger R. Reddel, M. John Kennedy, Toru Nakanishi, Allison F. Vitonis, Melissa C. Larson, Anna H. Wu, Helmut Deissler, Giuseppe Giannini, Barbara Wappenschmidt, Tomasz Byrski, M. Kamran Ikram, Natalia Antonenkova, Banu Arun, Peter Hillemanns, William Blot, Siti Zawiah Omar, Sue Healey, Trevor Cole, Cheng Har Yip, Matthias Dürst, Mark E. Robson, Roger L. Milne, Timothy R. Rebbeck, Jaana M. Hartikainen, Mieke Kriege, C. Ellen van der Schoot, Hansjoerg Plendl, Yasushi Yatabe, Jan C. Oosterwijk, Claus Høgdall, Rob A. E. M. Tollenaar, Jacek Gronwald, Yi Lu, Kate Lawrenson, Michael D. Stutz, Chia-Ni Hsiung, Alvaro N.A. Monteiro, Maren Weischer, Philipp Harter, Nicola Miller, Lisa B. Signorello, Katarzyna Durda, Peter Lichtner, Ritu Salani, Alfons Meindl, Montserrat Garcia-Closas, George Fountzilas, Uffe Birk Jensen, Thomas Brüning, Laura Baglietto, Anne M. van Altena, Kristine M. Hillman, Bernard Peissel, Trinidad Caldés, Rosemarie Davidson, Julian Barwell, Peter Devilee, Jenny Lester, Qiuyin Cai, Heiko Müller, Jyh Cherng Yu, Kerstin Rhiem, Muy Kheng Tea, Sharon A. Savage, Åke Borg, Daniel Vincent, Antoinette Hollestelle, Katarzyna Jaworska, Mat Adenan Noor Azmi, Yon Ko, Kimberly R. Kalli, Debra Frost, Martin Gore, Chiu-Chen Tseng, Georgia Chenevix-Trench, Pornthep Siriwanarangsan, Evelyn Despierre, Fergus J. Couch, Vijayalakshmi Shridhar, Artitaya Lophatananon, Amanda B. Spurdle, Joe Dennis, Ute Hamann, Vessela N. Kristensen, Frederik Marmé, Jonathan Tyrer, Arja Jukkola-Vuorinen, Wei Lu, Peter A. Fasching, Bruno Buecher, Kristiina Aittomäki, Kirsten B. Moysich, Lesley McGuffog, Mine S. Cicek, Guillermo Pita, Arjen R. Mensenkamp, Agnes Jager, Catherine M. Phelan, Jacques Simard, Ming-Feng Hou, Hiroji Iwata, James M. Flanagan, Elena Fineberg, Susan M. Domchek, Csilla Szabo, Diether Lambrechts, Anja Rudolph, Daehee Kang, Gottfried E. Konecny, Eitan Friedman, Argyrios Ziogas, Arto Mannermaa, Susan Peock, Matti A. Rookus, Christian F. Singer, Claire Mulot, Siranoush Manoukian, Johanna Rantala, Helen Tsimiklis, Gord Glendon, Pierre Laurent-Puig, Barbara Brouwers, Filomena Ficarazzi, Jonine D. Figueroa, Anne-Bine Skytte, Caroline Seynaeve, Christian Sutter, Rita K. Schmutzler, Julian Peto, Jeffrey N. Weitzel, Kathryn L. Terry, Børge G. Nordestgaard, Simon A. Gayther, Barbara Burwinkel, Ira Schwaab, Steven A. Narod, Elisabeth Wik, Ralf Bützow, Marco Montagna, Mark H. Greene, Linde M. Braaf, Janusz Menkiszak, Kamila Czene, Sarah Stewart-Brown, Kees E. P. van Roozendaal, Andreas Schneeweiss, Daniel Barrowdale, Elinor J. Sawyer, Alice S. Whittemore, Marc T. Goodman, Judith E. Brown, Kunle Odunsi, John L. Hopper, Nina Ditsch, Leon F.A.G. Massuger, Hermann Brenner, Joaquin J. Garcia, Xianshu Wang, Susan L. Slager, Aleksandra Tołoczko-Grabarek, Sylvie Mazoyer, Diana Eccles, Yik Ying Teo, Iwona K. Rzepecka, Bernardo Bonanni, Sara Margolin, Daniela Zaffaroni, Yew Ching Teh, Ans M Wvan Den Ouweland, Bent Ejlertsen, Maria Soller, Mitul Shah, Matthias W. Beckmann, Elizabeth M. Poole, J. Margriet Collée, Lorna Rodriguez-Rodriguez, Sandrina Lambrechts, Daniel W. Cramer, Douglas F. Easton, Virginie Caux-Moncoutier, Mads Thomassen, Keith Humphreys, ~, Landsteiner Laboratory, Clinical Haematology, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human Genetics, MUMC+: DA KG Lab Centraal Lab (9), Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Human genetics, CCA - Oncogenesis, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Clinical Genetics, Cardiothoracic Surgery, and Medical Oncology
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Telomerase ,Messenger ,Càncer d'ovari ,Estrogen receptor ,Aetiology, screening and detection [ONCOL 5] ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Alternative Splicing ,Biomarkers, Tumor ,Breast Neoplasms ,Case-Control Studies ,Chromatin ,DNA Methylation ,Female ,Gene Expression Profiling ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Humans ,Luciferases ,Oligonucleotide Array Sequence Analysis ,Ovarian Neoplasms ,Polymorphism, Single Nucleotide ,RNA, Messenger ,Real-Time Polymerase Chain Reaction ,Reverse Transcriptase Polymerase Chain Reaction ,Telomere ,Genetics ,BUCCAL CELLS ,0303 health sciences ,Tumor ,Telòmer ,GENETIC-VARIATION ,COMMON VARIANTS ,Single Nucleotide ,tert-clptm1l locus ,genome-wide association ,genetic-variation ,susceptibility loci ,buccal cells ,fibroblasts ,common variants ,carcinoma ,reverse-transcriptase htert ,metaanalysis ,Aetiology, screening and detection Immune Regulation [ONCOL 5] ,3. Good health ,Tumor Markers, Biological ,030220 oncology & carcinogenesis ,FIBROBLASTS ,SUSCEPTIBILITY LOCI ,CARCINOMA ,Single-nucleotide polymorphism ,Biology ,Article ,Càncer de mama ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Translational research [ONCOL 3] ,Ovarian cancer ,medicine ,Polymorphism ,Allele ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,030304 developmental biology ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,Breast cancer susceptibility ,Hereditary cancer and cancer-related syndromes [ONCOL 1] ,Translational research Genomic disorders and inherited multi-system disorders [ONCOL 3] ,medicine.disease ,Molecular biology ,TERT-CLPTM1L LOCUS ,Minor allele frequency ,RNA ,Biomarkers ,REVERSE-TRANSCRIPTASE HTERT - Abstract
Journal article 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. European Commission Seventh Framework Programme (agreement 223175-HEALTH-F2-2009-223175); Cancer Research UK (C1287/A10118 and C1287/A12014) peer-reviewed
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- 2013
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