Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast–ovarian cancer susceptibility locus
Nature Communications2016Vol. 7(1), pp. 12675–12675
Citations Over TimeTop 10% of 2016 papers
Kate Lawrenson, Siddhartha Kar, Karen McCue, Karoline Kuchenbaeker, Kyriaki Michailidou, Jonathan P. Tyrer, Jonathan Beesley, Susan J. Ramus, Qiyuan Li, Melissa K. Delgado, Janet M. Lee, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton‐Culver, Volker Arndt, Banu Arun, Brita Arver, Elisa V. Bandera, Monica Barile, Rósa B. Barkardóttir, Daniel Barrowdale, Matthias W. Beckmann, Javier Benı́tez, Andrew Berchuck, Maria Bisogna, Line Bjørge, Carl Blomqvist, William J. Blot, Natalia Bogdanova, Anders Bojesen, Stig E. Bojesen, Manjeet K. Bolla, Bernardo Bonanni, Anne‐Lise Børresen‐Dale, Hiltrud Brauch, Paul Brennan, Hermann Brenner, Fiona Bruinsma, Joan Brunet, Shaik Ahmad Buhari, Barbara Burwinkel, Ralf Bützow, Saundra S. Buys, Qiuyin Cai, Trinidad Caldés, Ian Campbell, Rikki Cannioto, Jenny Chang‐Claude, Jocelyne Chiquette, Ji‐Yeob Choi, Kathleen Claes, GEMO Study Collaborators, Marie- Agnès Collonge-Rame, Alexandre Damette, Emmanuelle Barouk-Simonet, Françoise Bonnet, Virginie Bubien, Nicolas Sévenet, Michel Longy, Pascaline Berthet, Dominique Vaur, Laurent Castéra, Sandra Fert Ferrer, Yves‐Jean Bignon, Nancy Uhrhammer, Fanny Coron, Laurence Faivre, Amandine Baurand, Caroline Jacquot, Geoffrey Bertolone, Sarab Lizard, Dominique Leroux, Hélène Dreyfus, Christine Rebischung, Magalie Peysselon, Jean‐Philippe Peyrat, Joëlle Fournier, Françoise Révillion, Claude Adenis, Laurence Venat‐Bouvet, Mélanie Léone, Nadia Boutry‐Kryza, Alain Calender, Sophie Giraud, Carole Verny-Pierre, Christine Lasset, Valérie Bonadona, Laure Barjhoux, Hagay Sobol, Violaine Bourdon, Tetsuro Noguchi, Audrey Remenieras, Isabelle Coupier, Pascal Pujol, Johanna Sokolowska, Myriam Bronner, Capucine Delnatte, Stéphane Bezieau, Véronique Mari, Marion Gauthier‐Villars, Bruno Buecher, Étienne Rouleau, Lisa Golmard, Virginie Moncoutier, Muriel Belotti, Antoine De Pauw, Camille Elan, Emmanuelle Fourme, Anne‐Marie Birot, Claire Saule, M Laurent, Claude Houdayer, Fabienne Lesueur, Noura Mebirouk, Florence Coulet, Chrystelle Colas, Florent Soubrier, Mathilde Warcoin, Fabienne Prieur, Marine Lebrun, Caroline Kientz, Danièle Muller, Jean‐Pierre Fricker, Christine Toulas, Rosine Guimbaud, Laurence Gladieff, V. Feillel, Isabelle Mortemousque, Brigitte Bressac–de Paillerets, Olivier Caron, Marine Guillaud-Bataille, Linda S. Cook, Angela Cox, Daniel W. Cramer, Simon S. Cross, Cezary Cybulski, Kamila Czene, Mary B. Daly, Francesca Damiola, Agnieszka Dansonka‐Mieszkowska, Hatef Darabi, Joe Dennis, Peter Devilee, Orland Dı́ez, Jennifer A. Doherty, Susan M. Domchek, Cecilia M. Dorfling, Thilo Dörk, Martine Dumont, Hans Ehrencrona, Bent Ejlertsen, Ian O. Ellis, EMBRACE, Helen Gregory, Zosia Miedzybrodzka, Patrick J. Morrison, Alan Donaldson, Mark T. Rogers, Michael J. Kennedy, Mary Porteous, Angela Brady, Julian Barwell, Claire Foo, Fiona Lalloo, Lucy Side, Jacqueline Eason, Alex Henderson, Lisa Walker, Jackie Cook, Katie Snape, Alex Murray, Emma McCann, Christoph Engel, Eunjung Lee, D. Gareth Evans, Peter A. Fasching, Lídia Feliubadaló, Jonine D. Figueroa, Dieter Flesch‐Janys, Olivia Fletcher, Henrik Flyger, Lenka Foretová, Florentia Fostira, William D. Foulkes, Brooke L. Fridley, Eitan Friedman, Debra Frost, Gaetana Gambino, Patricia A. Ganz, Judy E. Garber, Montserrat García‐Closas, Aleksandra Gentry‐Maharaj, Maya Ghoussaini, Graham G. Giles, Rosalind Glasspool, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González‐Neira, Ellen L. Goode, Marc T. Goodman, Mark H. Greene, Jacek Gronwald, Pascal Guénel, Christopher A. Haiman, Per Hall, Emily Hallberg, Ute Hamann, Thomas van Overeem Hansen, Patricia Harrington, Mikael Hartman, Norhashimah Hassan, Sue Healey, Matti A. Rookus, F.E. van Leeuwen, Lizet E. van der Kolk, Marjanka K. Schmidt, Nicola S. Russell, Jeffrey L. Lange, R. Wijnands, J. Margriet Collée, Maartje J. Hooning, Caroline Seynaeve, Carolien H. M. van Deurzen, Inge-Marie Obdeijn, Christi J. van Asperen, Rob A.�E.�M. Tollenaar, T. C. T. E. F. van Cronenburg, C. Marleen Kets, Margreet G.E.M. Ausems, Carmen C. van der Pol, Theo A.M. van Os, Quinten Waisfisz, Hanne Meijers‐Heijboer, E. Gómez, Jan C. Oosterwijk, M J E Mourits, Geertruida H. de Bock, Hans F. A. Vasen, Sabine Siesling, Janneke Verloop, Lucy Overbeek, Florian Heitz, Josef Herzog, Estrid Høgdall, Claus Høgdall, Frans B.L. Hogervorst, Antoinette Hollestelle, John L. Hopper, Peter J. Hulick, Tomasz Huzarski, Evgeny N. Imyanitov, KConFab Investigators, Stephen B. Fox, Judy Kirk, Geoffrey J. Lindeman, Melanie A. Price, Australian Ovarian Cancer Study Group, David D.L. Bowtell, Anna DeFazio, Penelope M. Webb, Claudine Isaacs, Hidemi Ito, Anna Jakubowska, Ramūnas Janavičius, Allan Jensen, Esther M. John, Nichola Johnson, Maria Kabisch, Daehee Kang, Miroslav Kapuscinski, Beth Y. Karlan, Sofia Khan, Lambertus A. Kiemeney, Susanne K. Kjær, Julia A. Knight, Irene Konstantopoulou, Veli‐Matti Kosma, Vessela Kristensen, Jolanta Kupryjańczyk, Ava Kwong, Miguel de la Hoya, Yael Laitman, Diether Lambrechts, Nhu D. Le, Kim De Leeneer, Jenny Lester, Douglas A. Levine, Jingmei Li, Annika Lindblom, Jirong Long, Artitaya Lophatananon, Jennifer T. Loud, Karen Lu, Jan Lubiński, Arto Mannermaa, Siranoush Manoukian, Loı̈c Le Marchand, Sara Margolin, Frederik Marmé, Leon F.A.G. Massuger, Keitaro Matsuo, Sylvie Mazoyer, Lesley McGuffog, Catriona McLean, Iain A. McNeish, Alfons Meindl, Usha Menon, Arjen R. Mensenkamp, Roger L. Milne, Marco Montagna, Kirsten B. Moysich, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, Roberta B. Ness, Susan L. Neuhausen, Heli Nevanlinna, Silje Nord, Robert L. Nussbaum, Kunle Odunsi, Kenneth Offit, Edith Oláh, Olufunmilayo I. Olopade, Janet E. Olson, Curtis Olswold, David M. O’Malley, Irene Orlow, Nick Orr, Ana Osório, Sue K. Park, Celeste Leigh Pearce, Tanja Pejović, Paolo Peterlongo, Georg Pfeiler, Catherine M. Phelan, Elizabeth M. Poole, Katri Pylkäs, Paolo Radice, Johanna Rantala, Muhammad Usman Rashid, Gad Rennert, Valerie Rhenius, Kerstin Rhiem, Harvey A. Risch, Gus Rodriguez, Mary Anne Rossing, Anja Rudolph, Helga B. Salvesen, Suleeporn Sangrajrang, Elinor J. Sawyer, Joellen M. Schildkraut, Marjanka K. Schmidt, Rita K. Schmutzler, Thomas A. Sellers, Caroline Seynaeve, Mitul Shah, Chen‐Yang Shen, Xiao‐Ou Shu, Weiva Sieh, Christian F. Singer, Olga M. Sinilnikova, Susan Slager, Honglin Song, Penny Soucy, Melissa C. Southey, Marie Stenmark‐Askmalm, Dominique Stoppa‐Lyonnet, Christian Sutter, Anthony J. Swerdlow, Sandrine Tchatchou, Manuel R. Teixeira, Soo‐Hwang Teo, Kathryn L. Terry, Mary Beth Terry, Mads Thomassen, Maria Grazia Tibiletti, Laima Tihomirova, Silvia Tognazzo, Amanda E. Toland, Ian Tomlinson, Diana Torres, Thérèse Truong, Chiu-Chen Tseng, Nadine Tung, Shelley S. Tworoger, Celine M. Vachon, Ans M.W. van den Ouweland, Helena C. van Doorn, Elizabeth J. van Rensburg, Laura J. van’t Veer, Adriaan Vanderstichele, Ignace Vergote, Joseph Vijai, Sophia Wang, Shan Wang‐Gohrke, Jeffrey N. Weitzel, Nicolas Wentzensen, Alice S. Whittemore, Hans Wildiers, Robert Winqvist, Anna H. Wu, Drakoulis Yannoukakos, Sook‐Yee Yoon, Jyh‐Cherng Yu, Wei Zheng, Ying Zheng, Kum Kum Khanna, Jacques Simard, Álvaro N.A. Monteiro, Juliet D. French, Fergus J. Couch, Matthew L. Freedman, Douglas F. Easton, Alison M. Dunning, Paul D.P. Pharoah, Stacey L. Edwards, Georgia Chenevix‐Trench, Antonis C. Antoniou, Simon A. Gayther
Abstract
A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-negative BC (P=1.1 × 10(-13)), BRCA1-associated BC (P=7.7 × 10(-16)) and triple negative BC (P-diff=2 × 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10(-3)) and ABHD8 (P<2 × 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
Related Papers
- → Identifying association model for single-nucleotide polymorphisms of ORAI1 gene for breast cancer(2014)22 cited
- → Single Nucleotide Polymorphisms (SNP) and SNP-SNP Interactions of the Surfactant Protein Genes Are Associated With Idiopathic Pulmonary Fibrosis in a Mexican Study Group; Comparison With Hypersensitivity Pneumonitis(2022)14 cited
- → Single Nucleotide Polymorphisms Interactions of the Surfactant Protein Genes Associated With Respiratory Distress Syndrome Susceptibility in Preterm Infants(2021)12 cited
- → Identification of SNPs Affecting Porcine Carcass Weight with the 60K SNP Chip(2013)4 cited
- → Construction and analysis of single nucleotide polymorphism–single nucleotide polymorphism interaction networks(2013)