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Title: 19p13.1 is a triple negative-specific breast cancer susceptibility locus
Authors: Stevens, Kristen N ×
Fredericksen, Zachary
Vachon, Celine M
Wang, Xianshu
Margolin, Sara
Lindblom, Annika
Nevanlinna, Heli
Greco, Dario
Aittomäki, Kristiina
Blomqvist, Carl
Chang-Claude, Jenny
Cox, Angela
Cross, Simon S
Reed, Malcom W
Hall, Per
Czene, Kamila
Ambrosone, Christine B
Ademuyiwa, Foluso
Hwang, Helena
Eccles, Diana M
Garcia-Closas, Montserrat
Vrieling, Alina
Figueroa, Jonine D
Sherman, Mark E
Lissowska, Jolanta
Devilee, Peter
Seynaeve, Caroline
Tollenaar, Rob A E M
Hooning, Maartje J
Andrulis, Irene L
Knight, Julia A
Glendon, Gord
Flesch-Janys, Dieter
Mulligan, Anna Marie
Winqvist, Robert
Pylkäs, Katri
Jukkola-Vuorinen, Arja
Grip, Mervi
John, Esther M
Miron, Alexander
Alnæs, Grethe Grenaker
Kristensen, Vessela
Børresen-Dale, Anne-Lise
Sinn, Hans-Peter
Giles, Graham G
Lambrechts, Diether
Baglietto, Laura
Hatse, Sigrid
McLean, Catriona A
Severi, Gianluca
Kosel, Matthew L
Pankratz, V S
Slager, Susan
Olson, Janet E
Wang-Gohrke, Shan
Radice, Paolo
Peterlongo, Paolo
Manoukian, Siranoush
Barile, Monica
Dieudonné, Anne-Sophie
Christiaens, Rose
Chenevix-Trench, Georgia
kConFab Investigators
AOCS Group
Beesley, Jonathan
Nickels, Stefan
Chen, Xiaoqing
Mannermaa, Arto
Kosma, Veli-Matti
Hartikainen, Jaana M
Soini, Ylermi
Easton, Douglas F
Couch, Fergus J
Brauch, Hiltrud
GENICA Network
Ko, Yon-Dschun
Fischer, Hans-Peter
Schmutzler, Rita K
Meindl, Alfons
Bartram, Claus R
Schott, Sarah
Engel, Christoph
Godwin, Andrew K
Weaver, Joellen
Pathak, Harsh B
Sharma, Priyanka
Brenner, Hermann
Müller, Heiko
Arndt, Volker
Stegmaier, Christa
Miron, Penelope
Yannoukakos, Drakoulis
Stavropoulou, Alexandra
Fountzilas, George
Gogas, Helen J
Swann, Ruth
Dwek, Miriam
Perkins, Annie
Milne, Roger L
Benítez, Javier
Zamora, María Pilar
Pérez, José Ignacio Arias
Bojesen, Stig E
Nielsen, Sune F
Nordestgaard, Børge G
Flyger, Henrik
Guénel, Pascal
Truong, Thérèse
Menegaux, Florence
Cordina-Duverger, Emilie
Burwinkel, Barbara
Marmé, Frederick
Schneeweiss, Andreas
Sohn, Christof
Sawyer, Elinor
Tomlinson, Ian
Kerin, Michael J
Peto, Julian
Johnson, Nichola
Fletcher, Olivia
Dos Santos Silva, Isabel
Fasching, Peter A
Beckmann, Matthias W
Hartmann, Arndt
Ekici, Arif B
Lophatananon, Artitaya
Muir, Kenneth
Puttawibul, Puttisak
Wiangnon, Surapon
Schmidt, Marjanka K
Broeks, Annegien
Braaf, Linde M
Rosenberg, Efraim H
Hopper, John L
Apicella, Carmel
Park, Daniel J
Southey, Melissa C
Swerdlow, Anthony J
Ashworth, Alan
Orr, Nicholas
Schoemaker, Minouk J
Anton-Culver, Hoda
Ziogas, Argyrios
Bernstein, Leslie
Dur, Christina Clarke
Shen, Chen-Yang
Yu, Jyh-Cherng
Hsu, Huan-Ming
Hsiung, Chia-Ni
Hamann, Ute
Dünnebier, Thomas
Rüdiger, Thomas
Ulmer, Hans Ulrich
Pharoah, Paul P
Dunning, Alison M
Humphreys, Manjeet K
Wang, Qin #
Issue Date: 1-Apr-2012
Publisher: Waverly Press
Series Title: Cancer Research vol:72 issue:7 pages:1795-1803
Abstract: The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 × 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 × 10(-7)). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18-1.33; P = 3.31 × 10(-13)]. Thus, 19p13.1 is the first triple-negative-specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways.
URI: 
ISSN: 0008-5472
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Surgical Oncology
Gynaecological Oncology
Laboratory of Experimental Oncology
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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