Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

Jingjing Liu, Wendy J.C. Prager-van der Smissen, J. Margriet Collée, Manjeet K. Bolla, Qin Wang, Kyriaki Michailidou, Joe Dennis, Thomas U. Ahearn, Kristiina Aittomäki, Christine B. Ambrosone, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Norbert Arnold, Kristan J. Aronson, Annelie Augustinsson, Päivi Auvinen, Heiko Becher, Matthias W. BeckmannSabine Behrens, Marina Bermisheva, Leslie Bernstein, Natalia V. Bogdanova, Nadja Bogdanova-Markov, Stig E. Bojesen, Hiltrud Brauch, Hermann Brenner, Ignacio Briceno, Sara Y. Brucker, Thomas Brüning, Barbara Burwinkel, Qiuyin Cai, Hui Cai, Daniele Campa, Federico Canzian, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Ji Yeob Choi, Melissa Christiaens, Christine L. Clarke, Fergus J. Couch, Kamila Czene, Mary B. Daly, Peter Devilee, Isabel Dos-Santos-Silva, Miriam Dwek, Diana M. Eccles, A. Heather Eliassen, Peter A. Fasching, Jonine Figueroa, Henrik Flyger, Lin Fritschi, Manuela Gago-Dominguez, Susan M. Gapstur, Montserrat García-Closas, José A. García-Sáenz, Mia M. Gaudet, Graham G. Giles, Mark S. Goldberg, David E. Goldgar, Pascal Guénel, Christopher A. Haiman, Niclas Håkansson, Per Hall, Patricia A. Harrington, Steven N. Hart, Mikael Hartman, Peter Hillemanns, John L. Hopper, Ming Feng Hou, David J. Hunter, Dezheng Huo, Hidemi Ito, Motoki Iwasaki, Milena Jakimovska, Anna Jakubowska, Esther M. John, Rudolf Kaaks, Daehee Kang, Renske Keeman, Elza Khusnutdinova, Sung Won Kim, Peter Kraft, Vessela N. Kristensen, Allison W. Kurian, Loic Le Marchand, Jingmei Li, Annika Lindblom, Artitaya Lophatananon, Robert N. Luben, Jan Lubiński, Arto Mannermaa, Mehdi Manoochehri, Siranoush Manoukian, Sara Margolin, Shivaani Mariapun, Keitaro Matsuo, Tabea Maurer, Dimitrios Mavroudis, Alfons Meindl, Usha Menon, Roger L. Milne, Kenneth Muir, Anna Marie Mulligan, Susan L. Neuhausen, Heli Nevanlinna, Kenneth Offit, Olufunmilayo I. Olopade, Janet E. Olson, Håkan Olsson, Nick Orr, Sue K. Park, Paolo Peterlongo, Julian Peto, Dijana Plaseska-Karanfilska, Nadege Presneau, Brigitte Rack, Rohini Rau-Murthy, Gad Rennert, Hedy S. Rennert, Valerie Rhenius, Atocha Romero, Matthias Ruebner, Emmanouil Saloustros, Rita K. Schmutzler, Andreas Schneeweiss, Christopher Scott, Mitul Shah, Chen Yang Shen, Xiao Ou Shu, Jacques Simard, Christof Sohn, Melissa C. Southey, John J. Spinelli, Rulla M. Tamimi, William J. Tapper, Soo H. Teo, Mary Beth Terry, Diana Torres, Thérèse Truong, Michael Untch, Celine M. Vachon, Christi J. van Asperen, Alicja Wolk, Taiki Yamaji, Wei Zheng, Argyrios Ziogas, Elad Ziv, Gabriela Torres-Mejía, Thilo Dörk, Anthony J. Swerdlow, Ute Hamann, Marjanka K. Schmidt, Alison M. Dunning, Paul D.P. Pharoah, Douglas F. Easton, Maartje J. Hooning, John W.M. Martens, Antoinette Hollestelle, NBCS Collaborators, ABCTB Investigators

Research output: Contribution to journalArticleResearchpeer-review

Abstract

In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.

Original languageEnglish
Article number9688
Number of pages14
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 16 Jun 2020

Cite this