与雌激素受体阴性乳腺癌风险相关的十种变异的鉴定。
Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.
作者信息
Milne Roger L, Kuchenbaecker Karoline B, Michailidou Kyriaki, Beesley Jonathan, Kar Siddhartha, Lindström Sara, Hui Shirley, Lemaçon Audrey, Soucy Penny, Dennis Joe, Jiang Xia, Rostamianfar Asha, Finucane Hilary, Bolla Manjeet K, McGuffog Lesley, Wang Qin, Aalfs Cora M, Adams Marcia, Adlard Julian, Agata Simona, Ahmed Shahana, Ahsan Habibul, Aittomäki Kristiina, Al-Ejeh Fares, Allen Jamie, Ambrosone Christine B, Amos Christopher I, Andrulis Irene L, Anton-Culver Hoda, Antonenkova Natalia N, Arndt Volker, Arnold Norbert, Aronson Kristan J, Auber Bernd, Auer Paul L, Ausems Margreet G E M, Azzollini Jacopo, Bacot François, Balmaña Judith, Barile Monica, Barjhoux Laure, Barkardottir Rosa B, Barrdahl Myrto, Barnes Daniel, Barrowdale Daniel, Baynes Caroline, Beckmann Matthias W, Benitez Javier, Bermisheva Marina, Bernstein Leslie, Bignon Yves-Jean, Blazer Kathleen R, Blok Marinus J, Blomqvist Carl, Blot William, Bobolis Kristie, Boeckx Bram, Bogdanova Natalia V, Bojesen Anders, Bojesen Stig E, Bonanni Bernardo, Børresen-Dale Anne-Lise, Bozsik Aniko, Bradbury Angela R, Brand Judith S, Brauch Hiltrud, Brenner Hermann, Bressac-de Paillerets Brigitte, Brewer Carole, Brinton Louise, Broberg Per, Brooks-Wilson Angela, Brunet Joan, Brüning Thomas, Burwinkel Barbara, Buys Saundra S, Byun Jinyoung, Cai Qiuyin, Caldés Trinidad, Caligo Maria A, Campbell Ian, Canzian Federico, Caron Olivier, Carracedo Angel, Carter Brian D, Castelao J Esteban, Castera Laurent, Caux-Moncoutier Virginie, Chan Salina B, Chang-Claude Jenny, Chanock Stephen J, Chen Xiaoqing, Cheng Ting-Yuan David, Chiquette Jocelyne, Christiansen Hans, Claes Kathleen B M, Clarke Christine L, Conner Thomas, Conroy Don M, Cook Jackie, Cordina-Duverger Emilie, Cornelissen Sten, Coupier Isabelle, Cox Angela, Cox David G, Cross Simon S, Cuk Katarina, Cunningham Julie M, Czene Kamila, Daly Mary B, Damiola Francesca, Darabi Hatef, Davidson Rosemarie, De Leeneer Kim, Devilee Peter, Dicks Ed, Diez Orland, Ding Yuan Chun, Ditsch Nina, Doheny Kimberly F, Domchek Susan M, Dorfling Cecilia M, Dörk Thilo, Dos-Santos-Silva Isabel, Dubois Stéphane, Dugué Pierre-Antoine, Dumont Martine, Dunning Alison M, Durcan Lorraine, Dwek Miriam, Dworniczak Bernd, Eccles Diana, Eeles Ros, Ehrencrona Hans, Eilber Ursula, Ejlertsen Bent, Ekici Arif B, Eliassen A Heather, Engel Christoph, Eriksson Mikael, Fachal Laura, Faivre Laurence, Fasching Peter A, Faust Ulrike, Figueroa Jonine, Flesch-Janys Dieter, Fletcher Olivia, Flyger Henrik, Foulkes William D, Friedman Eitan, Fritschi Lin, Frost Debra, Gabrielson Marike, Gaddam Pragna, Gammon Marilie D, Ganz Patricia A, Gapstur Susan M, Garber Judy, Garcia-Barberan Vanesa, García-Sáenz José A, Gaudet Mia M, Gauthier-Villars Marion, Gehrig Andrea, Georgoulias Vassilios, Gerdes Anne-Marie, Giles Graham G, Glendon Gord, Godwin Andrew K, Goldberg Mark S, Goldgar David E, González-Neira Anna, Goodfellow Paul, Greene Mark H, Alnæs Grethe I Grenaker, Grip Mervi, Gronwald Jacek, Grundy Anne, Gschwantler-Kaulich Daphne, Guénel Pascal, Guo Qi, Haeberle Lothar, Hahnen Eric, Haiman Christopher A, Håkansson Niclas, Hallberg Emily, Hamann Ute, Hamel Nathalie, Hankinson Susan, Hansen Thomas V O, Harrington Patricia, Hart Steven N, Hartikainen Jaana M, Healey Catherine S, Hein Alexander, Helbig Sonja, Henderson Alex, Heyworth Jane, Hicks Belynda, Hillemanns Peter, Hodgson Shirley, Hogervorst Frans B, Hollestelle Antoinette, Hooning Maartje J, Hoover Bob, Hopper John L, Hu Chunling, Huang Guanmengqian, Hulick Peter J, Humphreys Keith, Hunter David J, Imyanitov Evgeny N, Isaacs Claudine, Iwasaki Motoki, Izatt Louise, Jakubowska Anna, James Paul, Janavicius Ramunas, Janni Wolfgang, Jensen Uffe Birk, John Esther M, Johnson Nichola, Jones Kristine, Jones Michael, Jukkola-Vuorinen Arja, Kaaks Rudolf, Kabisch Maria, Kaczmarek Katarzyna, Kang Daehee, Kast Karin, Keeman Renske, Kerin Michael J, Kets Carolien M, Keupers Machteld, Khan Sofia, Khusnutdinova Elza, Kiiski Johanna I, Kim Sung-Won, Knight Julia A, Konstantopoulou Irene, Kosma Veli-Matti, Kristensen Vessela N, Kruse Torben A, Kwong Ava, Lænkholm Anne-Vibeke, Laitman Yael, Lalloo Fiona, Lambrechts Diether, Landsman Keren, Lasset Christine, Lazaro Conxi, Le Marchand Loic, Lecarpentier Julie, Lee Andrew, Lee Eunjung, Lee Jong Won, Lee Min Hyuk, Lejbkowicz Flavio, Lesueur Fabienne, Li Jingmei, Lilyquist Jenna, Lincoln Anne, Lindblom Annika, Lissowska Jolanta, Lo Wing-Yee, Loibl Sibylle, Long Jirong, Loud Jennifer T, Lubinski Jan, Luccarini Craig, Lush Michael, MacInnis Robert J, Maishman Tom, Makalic Enes, Kostovska Ivana Maleva, Malone Kathleen E, Manoukian Siranoush, Manson JoAnn E, Margolin Sara, Martens John W M, Martinez Maria Elena, Matsuo Keitaro, Mavroudis Dimitrios, Mazoyer Sylvie, McLean Catriona, Meijers-Heijboer Hanne, Menéndez Primitiva, Meyer Jeffery, Miao Hui, Miller Austin, Miller Nicola, Mitchell Gillian, Montagna Marco, Muir Kenneth, Mulligan Anna Marie, Mulot Claire, Nadesan Sue, Nathanson Katherine L, Neuhausen Susan L, Nevanlinna Heli, Nevelsteen Ines, Niederacher Dieter, Nielsen Sune F, Nordestgaard Børge G, Norman Aaron, Nussbaum Robert L, Olah Edith, Olopade Olufunmilayo I, Olson Janet E, Olswold Curtis, Ong Kai-Ren, Oosterwijk Jan C, Orr Nick, Osorio Ana, Pankratz V Shane, Papi Laura, Park-Simon Tjoung-Won, Paulsson-Karlsson Ylva, Lloyd Rachel, Pedersen Inge Søkilde, Peissel Bernard, Peixoto Ana, Perez Jose I A, Peterlongo Paolo, Peto Julian, Pfeiler Georg, Phelan Catherine M, Pinchev Mila, Plaseska-Karanfilska Dijana, Poppe Bruce, Porteous Mary E, Prentice Ross, Presneau Nadege, Prokofieva Darya, Pugh Elizabeth, Pujana Miquel Angel, Pylkäs Katri, Rack Brigitte, Radice Paolo, Rahman Nazneen, Rantala Johanna, Rappaport-Fuerhauser Christine, Rennert Gad, Rennert Hedy S, Rhenius Valerie, Rhiem Kerstin, Richardson Andrea, Rodriguez Gustavo C, Romero Atocha, Romm Jane, Rookus Matti A, Rudolph Anja, Ruediger Thomas, Saloustros Emmanouil, Sanders Joyce, Sandler Dale P, Sangrajrang Suleeporn, Sawyer Elinor J, Schmidt Daniel F, Schoemaker Minouk J, Schumacher Fredrick, Schürmann Peter, Schwentner Lukas, Scott Christopher, Scott Rodney J, Seal Sheila, Senter Leigha, Seynaeve Caroline, Shah Mitul, Sharma Priyanka, Shen Chen-Yang, Sheng Xin, Shimelis Hermela, Shrubsole Martha J, Shu Xiao-Ou, Side Lucy E, Singer Christian F, Sohn Christof, Southey Melissa C, Spinelli John J, Spurdle Amanda B, Stegmaier Christa, Stoppa-Lyonnet Dominique, Sukiennicki Grzegorz, Surowy Harald, Sutter Christian, Swerdlow Anthony, Szabo Csilla I, Tamimi Rulla M, Tan Yen Y, Taylor Jack A, Tejada Maria-Isabel, Tengström Maria, Teo Soo H, Terry Mary B, Tessier Daniel C, Teulé Alex, Thöne Kathrin, Thull Darcy L, Tibiletti Maria Grazia, Tihomirova Laima, Tischkowitz Marc, Toland Amanda E, Tollenaar Rob A E M, Tomlinson Ian, Tong Ling, Torres Diana, Tranchant Martine, Truong Thérèse, Tucker Kathy, Tung Nadine, Tyrer Jonathan, Ulmer Hans-Ulrich, Vachon Celine, van Asperen Christi J, Van Den Berg David, van den Ouweland Ans M W, van Rensburg Elizabeth J, Varesco Liliana, Varon-Mateeva Raymonda, Vega Ana, Viel Alessandra, Vijai Joseph, Vincent Daniel, Vollenweider Jason, Walker Lisa, Wang Zhaoming, Wang-Gohrke Shan, Wappenschmidt Barbara, Weinberg Clarice R, Weitzel Jeffrey N, Wendt Camilla, Wesseling Jelle, Whittemore Alice S, Wijnen Juul T, Willett Walter, Winqvist Robert, Wolk Alicja, Wu Anna H, Xia Lucy, Yang Xiaohong R, Yannoukakos Drakoulis, Zaffaroni Daniela, Zheng Wei, Zhu Bin, Ziogas Argyrios, Ziv Elad, Zorn Kristin K, Gago-Dominguez Manuela, Mannermaa Arto, Olsson Håkan, Teixeira Manuel R, Stone Jennifer, Offit Kenneth, Ottini Laura, Park Sue K, Thomassen Mads, Hall Per, Meindl Alfons, Schmutzler Rita K, Droit Arnaud, Bader Gary D, Pharoah Paul D P, Couch Fergus J, Easton Douglas F, Kraft Peter, Chenevix-Trench Georgia, García-Closas Montserrat, Schmidt Marjanka K, Antoniou Antonis C, Simard Jacques
机构信息
Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
出版信息
Nat Genet. 2017 Dec;49(12):1767-1778. doi: 10.1038/ng.3785. Epub 2017 Oct 23.
Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
大多数常见的乳腺癌易感变异是通过对主要为雌激素受体（ER）阳性疾病的全基因组关联研究（GWAS）确定的。我们开展了一项GWAS，研究对象包括21468例ER阴性病例和100594例对照，并纳入了18908例BRCA1突变携带者（9414例患有乳腺癌），所有研究对象均为欧洲血统。我们在P < 5×10时确定了9个新位点的10个变异的独立关联。在P < 0.05时，我们重复了先前在ER阴性疾病或BRCA1突变携带者GWAS中报道的11个变异中的10个的关联，并观察到其他研究确定的105个易感变异与ER阴性疾病存在一致关联。这125个变异解释了这种乳腺癌亚型约16%的家族风险。ER阴性乳腺癌风险与BRCA1突变携带者的乳腺癌风险之间存在高度遗传相关性（0.72）。这些发现可能会改善风险预测，并为进一步的精细定位和功能研究提供信息，以更好地理解ER阴性乳腺癌的生物学基础。
Zotero 插件