Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

作者：on behalf of EMBRACE, Chenjie Zeng, behalf of GEMO Study Collaborators, on behalf of HEBON, on behalf of KConFab, AOCS Investigators, Xingyi Guo, Jirong Long, Karoline Kuchenbaecker, Arnaud Droit, Kyriaki Michailidou, Maya Ghoussaini, Siddhartha Kar, Adam N. Freeman, John L. Hopper, Roger L. Milne, Manjeet K. Bolla, Qin Wang, Joe Dennis, Simona Agata, Shahana Ahmed, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton‐Culver, Natalia Antonenkova, Aðalgeir Arason, Volker Arndt, Banu Arun, Brita Arver, François Bacot, Daniel Barrowdale, Caroline Baynes, Alicia Beeghly‐Fadiel, Javier Benı́tez, Marina Bermisheva, Carl Blomqvist, William J. Blot, Natalia Bogdanova, Stig E. Bojesen, Bernardo Bonanni, Anne‐Lise Børresen‐Dale, Judith S. Brand, Hiltrud Brauch, Paul Brennan, Hermann Brenner, Annegien Broeks, Thomas Brüning, Barbara Burwinkel, Saundra S. Buys, Qiuyin Cai, Trinidad Caldés, Ian Campbell, Jane Carpenter, Jenny Chang‐Claude, Ji‐Yeob Choi, Kathleen Claes, Christine L. Clarke, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Miguel de la Hoya, Kim De Leeneer, Peter Devilee, Orland Dı́ez, Susan M. Domchek, Michele M. Doody, Cecilia M. Dorfling, Thilo Dörk, Isabel dos‐Santos‐Silva, Martine Dumont, Miriam Dwek, Bernd Dworniczak, Kathleen M. Egan, Ursula Eilber, Zakaria Einbeigi, Bent Ejlertsen, Steve Ellis, Debra Frost, Fiona Lalloo, Peter A. Fasching, Jonine D. Figueroa, Henrik Flyger, Michael Friedländer, Eitan Friedman, Gaetana Gambino, Yu‐Tang Gao, Judy E. Garber, Montserrat García‐Closas, Andrea Gehrig, Francesca Damiola, Fabienne Lesueur, Sylvie Mazoyer, Dominique Stoppa‐Lyonnet, Graham G. Giles, Andrew K. Godwin, David E. Goldgar, Anna González‐Neira, Mark H. Greene, Pascal Guénel, Lothar Haeberle, Christopher A. Haiman, Emily Hallberg, Ute Hamann, Thomas van Overeem Hansen, Steven N. Hart, Jaana M. Hartikainen, Mikael Hartman, Norhashimah Hassan, Sue Healey, Frans B.L. Hogervorst, Senno Verhoef, Carolyn B. Hendricks, Peter Hillemanns, Antoinette Hollestelle, Peter J. Hulick, David J. Hunter, Evgeny N. Imyanitov, Claudine Isaacs, Hidemi Ito, Anna Jakubowska, Ramunas Janavicius, Katarzyna Jaworska–Bieniek, Uffe Birk Jensen, Esther M. John, Charles Joly Beauparlant, Michael E. Jones, Maria Kabisch, Daehee Kang, Beth Y. Karlan, Saila Kauppila, Michael J. Kerin, Sofia Khan, Э. К. Хуснутдинова, Julia A. Knight, Irene Konstantopoulou, Peter Kraft, Ava Kwong, Yael Laitman, Diether Lambrechts, Conxi Lázaro, Loı̈c Le Marchand, Chuen Neng Lee, Min Hyuk Lee, Jenny Lester, Jingmei Li, Annelie Liljegren, Annika Lindblom, Artitaya Lophatananon, Jan Lubiński, Phuong L. Mai, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Frederik Marmé, Keitaro Matsuo, Lesley McGuffog, Alfons Meindl, F. Ménégaux, Marco Montagna, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Silje Nord, Robert L. Nussbaum, Kenneth Offit, Edith Oláh, Olufunmilayo I. Olopade, Curtis Olswold, Ana Osório, Laura Papi, Tjoung‐Won Park‐Simon, Ylva Paulsson-Karlsson, Stéphanie Peeters, Bernard Peissel, Paolo Peterlongo, Julian Peto, Georg Pfeiler, Catherine M. Phelan, Nadège Presneau, Paolo Radice, Nazneen Rahman, Susan J. Ramus, Muhammad Usman Rashid, Gad Rennert, Kerstin Rhiem, Anja Rudolph, Ritu Salani, Suleeporn Sangrajrang, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Minouk J. Schoemaker, Peter Schürmann, Caroline Seynaeve, Chen‐Yang Shen, Martha J. Shrubsole, Xiao-Ou Shu, Alice J. Sigurdson, Christian F. Singer, Susan Slager, Penny Soucy, Melissa C. Southey, Doris Steinemann, Anthony J. Swerdlow, Csilla I. Szabo, Sandrine Tchatchou, Manuel R. Teixeira, Soo‐Hwang Teo, Mary Beth Terry, Daniel C. Tessier, Àlex Teulé, Mads Thomassen, Laima Tihomirova, Marc Tischkowitz, Amanda E. Toland, Nadine Tung, Clare Turnbull, Ans M.W. van den Ouweland, Elizabeth J. van Rensburg, David ven den Berg, Joseph Vijai, Shan Wang‐Gohrke, Jeffrey N. Weitzel, Alice S. Whittemore, Robert Winqvist, Tien Yin Wong, Anna H. Wu, Drakoulis Yannoukakos, Jyh-Cherng Yu, Paul D.P. Pharoah, Per Hall, Georgia Chenevix‐Trench, Alison M. Dunning, Jacques Simard, Fergus J. Couch, Antonis C. Antoniou, Douglas F. Easton, Wei Zheng · 发表于：Breast Cancer Research · 年份：2016 · DOI：10.1186/s13058-016-0718-0 · 被引用次数：76 · 研究领域：BRCA gene mutations in cancer、Genetic Associations and Epidemiology、Genomics and Rare Diseases

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P <...