The University of Southampton
University of Southampton Institutional Repository

Genome-wide association studies identify four ER negative–specific breast cancer risk loci

Genome-wide association studies identify four ER negative–specific breast cancer risk loci
Genome-wide association studies identify four ER negative–specific breast cancer risk loci
Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.
1061-4036
392-398
Garcia-Closas, Montserrat
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Couch, Fergus J.
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Sherman, Mark E.
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Garcia-Closas, Montserrat, Couch, Fergus J., Lindstrom, Sara, Michailidou, Kyriaki, Schmidt, Marjanka K., Brook, Mark N., Orr, Nick, Rhie, Suhn Kyong, Riboli, Elio, Feigelson, Heather S., Le Marchand, Loic, Buring, Julie E., Eccles, Diana, Miron, Penelope, Fasching, Peter A., Brauch, Hiltrud, Chang-Claude, Jenny, Carpenter, Jane, Godwin, Andrew K., Nevanlinna, Heli, Giles, Graham G., Cox, Angela, Hopper, John L., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Dicks, Ed, Howat, Will J., Schoof, Nils, Bojesen, Stig E., Lambrechts, Diether, Broeks, Annegien, Andrulis, Irene L., Guénel, Pascal, Burwinkel, Barbara, Sawyer, Elinor J., Hollestelle, Antoinette, Fletcher, Olivia, Winqvist, Robert, Brenner, Hermann, Mannermaa, Arto, Hamann, Ute, Meindl, Alfons, Lindblom, Annika, Zheng, Wei, Devillee, Peter, Goldberg, Mark S., Lubinski, Jan, Kristensen, Vessela, Swerdlow, Anthony, Anton-Culver, Hoda, Dörk, Thilo, Muir, Kenneth, Matsuo, Keitaro, Wu, Anna H., Radice, Paolo, Teo, Soo Hwang, Shu, Xiao-Ou, Blot, William, Kang, Daehee, Hartman, Mikael, Sangrajrang, Suleeporn, Shen, Chen-Yang, Southey, Melissa C., Park, Daniel J., Hammet, Fleur, Stone, Jennifer, Veer, Laura J. Van't, Rutgers, Emiel J., Lophatananon, Artitaya, Stewart-Brown, Sarah, Siriwanarangsan, Pornthep, Peto, Julian, Schrauder, Michael G., Ekici, Arif B., Beckmann, Matthias W., dos Santos Silva, Isabel, Johnson, Nichola, Warren, Helen, Tomlinson, Ian, Kerin, Michael J, Miller, Nicola, Marme, Federick, Schneeweiss, Andreas, Sohn, Christof, Truong, Therese, Laurent-Puig, Pierre, Kerbrat, Pierre, Nordestgaard, Børge G., Nielsen, Sune F., Flyger, Henrik, Milne, Roger L., Perez, Jose Ignacio Arias, Menéndez, Primitiva, Müller, Heiko, Arndt, Volker, Stegmaier, Christa, Lichtner, Peter, Lochmann, Magdalena, Justenhoven, Christina, Ko, Yon-Dschun, Muranen, Taru A., Aittomäki, Kristiina, Blomqvist, Carl, Greco, Dario, Heikkinen, Tuomas, Ito, Hidemi, Iwata, Hiroji, Yatabe, Yasushi, Antonenkova, Natalia N., Margolin, Sara, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Balleine, Rosemary, Tseng, Chiu-Chen, Berg, David Van Den, Stram, Daniel O., Neven, Patrick, Dieudonné, Anne-Sophie, Leunen, Karin, Rudolph, Anja, Nickels, Stefan, Flesch-Janys, Dieter, Peterlongo, Paolo, Peissel, Bernard, Bernard, Loris, Olson, Janet E., Wang, Xianshu, Stevens, Kristen, Severi, Gianluca, Baglietto, Laura, McLean, Catriona, Coetzee, Gerhard A., Feng, Ye, Henderson, Brian E., Schumacher, Fredrick, Bogdanova, Natalia V., Labrèche, France, Dumont, Martine, Yip, Cheng Har, Taib, Nur Aishah Mohd, Cheng, Ching-Yu, Shrubsole, Martha, Long, Jirong, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Kauppila, Saila, Knight, Julia A., Glendon, Gord, Mulligan, Anna Marie, Tollenaar, Robertus A. E. M., Seynaeve, Caroline M., Kriege, Mieke, Hooning, Maartje J., van den Ouweland, Ans M. W., van Deurzen, Carolien H. M., Lu, Wei, Gao, Yu-Tang, Cai, Hui, Balasubramanian, Sabapathy P., Cross, Simon S., Reed, Malcolm W. R., Signorello, Lisa, Cai, Qiuyin, Shah, Mitul, Miao, Hui, Chan, Ching Wan, Chia, Kee Seng, Jakubowska, Anna, Jaworska, Katarzyna, Durda, Katarzyna, Hsiung, Chia-Ni, Wu, Pei-Ei, Yu, Jyh-Cherng, Ashworth, Alan, Jones, Michael, Tessier, Daniel C., González-Neira, Anna, Pita, Guillermo, Alonso, M. Rosario, Vincent, Daniel, Bacot, Francois, Ambrosone, Christine B., Bandera, Elisa V., John, Esther M., Chen, Gary K., Hu, Jennifer J., Rodriguez-Gil, Jorge L., Bernstein, Leslie, Press, Michael F., Ziegler, Regina G., Millikan, Robert M., Deming-Halverson, Sandra L., Nyante, Sarah, Ingles, Sue A., Waisfisz, Quinten, Tsimiklis, Helen, Makalic, Enes, Schmidt, Daniel, Bui, Minh, Gibson, Lorna, Müller-Myhsok, Bertram, Schmutzler, Rita K., Hein, Rebecca, Dahmen, Norbert, Beckmann, Lars, Aaltonen, Kirsimari, Czene, Kamila, Irwanto, Astrid, Liu, Jianjun, Turnbull, Clare, Rahman, Nazneen, Meijers-Heijboer, Hanne, Uitterlinden, Andre G., Rivadeneira, Fernando, Olswold, Curtis, Slager, Susan, Pilarski, Robert, Ademuyiwa, Foluso, Konstantopoulou, Irene, Martin, Nicholas G., Montgomery, Grant W., Slamon, Dennis J., Rauh, Claudia, Lux, Michael P., Jud, Sebastian M., Bruning, Thomas, Weaver, JoEllen, Sharma, Priyanka, Pathak, Harsh, Tapper, Will, Gerty, Sue, Durcan, Lorraine, Trichopoulos, Dimitrios, Tumino, Rosario, Peeters, Petra H., Kaaks, Rudolf, Campa, Daniele, Canzian, Federico, Weiderpass, Elisabete, Johansson, Mattias, Khaw, Kay-Tee, Travis, Ruth, Clavel-Chapelon, Françoise, Kolonel, Laurence N., Chen, Constance, Beck, Andy, Hankinson, Susan E., Berg, Christine D., Hoover, Robert N., Lissowska, Jolanta, Figueroa, Jonine D., Chasman, Daniel I., Gaudet, Mia M., Diver, W. Ryan, Willett, Walter C., Hunter, David J., Simard, Jacques, Benitez, Javier, Dunning, Alison M., Sherman, Mark E., Chenevix-Trench, Georgia, Chanock, Stephen J., Hall, Per, Pharoah, Paul D. P., Vachon, Celine, Easton, Douglas F., Haiman, Christopher A. and Kraft, Peter (2013) Genome-wide association studies identify four ER negative–specific breast cancer risk loci. Nature Genetics, 45 (4), 392-398. (doi:10.1038/ng.2561). (PMID:23535733)

Record type: Article

Abstract

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

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e-pub ahead of print date: 27 March 2013
Published date: April 2013
Organisations: Cancer Sciences, Human Development & Health

Identifiers

Local EPrints ID: 352327
URI: http://eprints.soton.ac.uk/id/eprint/352327
ISSN: 1061-4036
PURE UUID: 81518bfc-306f-450b-b700-4fbbcaedcede
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169
ORCID for Will Tapper: ORCID iD orcid.org/0000-0002-5896-1889

Catalogue record

Date deposited: 09 May 2013 15:15
Last modified: 23 Jul 2022 01:45

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Contributors

Author: Montserrat Garcia-Closas
Author: Fergus J. Couch
Author: Sara Lindstrom
Author: Kyriaki Michailidou
Author: Marjanka K. Schmidt
Author: Mark N. Brook
Author: Nick Orr
Author: Suhn Kyong Rhie
Author: Elio Riboli
Author: Heather S. Feigelson
Author: Loic Le Marchand
Author: Julie E. Buring
Author: Diana Eccles ORCID iD
Author: Penelope Miron
Author: Peter A. Fasching
Author: Hiltrud Brauch
Author: Jenny Chang-Claude
Author: Jane Carpenter
Author: Andrew K. Godwin
Author: Heli Nevanlinna
Author: Graham G. Giles
Author: Angela Cox
Author: John L. Hopper
Author: Manjeet K. Bolla
Author: Qin Wang
Author: Joe Dennis
Author: Ed Dicks
Author: Will J. Howat
Author: Nils Schoof
Author: Stig E. Bojesen
Author: Diether Lambrechts
Author: Annegien Broeks
Author: Irene L. Andrulis
Author: Pascal Guénel
Author: Barbara Burwinkel
Author: Elinor J. Sawyer
Author: Antoinette Hollestelle
Author: Olivia Fletcher
Author: Robert Winqvist
Author: Hermann Brenner
Author: Arto Mannermaa
Author: Ute Hamann
Author: Alfons Meindl
Author: Annika Lindblom
Author: Wei Zheng
Author: Peter Devillee
Author: Mark S. Goldberg
Author: Jan Lubinski
Author: Vessela Kristensen
Author: Anthony Swerdlow
Author: Hoda Anton-Culver
Author: Thilo Dörk
Author: Kenneth Muir
Author: Keitaro Matsuo
Author: Anna H. Wu
Author: Paolo Radice
Author: Soo Hwang Teo
Author: Xiao-Ou Shu
Author: William Blot
Author: Daehee Kang
Author: Mikael Hartman
Author: Suleeporn Sangrajrang
Author: Chen-Yang Shen
Author: Melissa C. Southey
Author: Daniel J. Park
Author: Fleur Hammet
Author: Jennifer Stone
Author: Laura J. Van't Veer
Author: Emiel J. Rutgers
Author: Artitaya Lophatananon
Author: Sarah Stewart-Brown
Author: Pornthep Siriwanarangsan
Author: Julian Peto
Author: Michael G. Schrauder
Author: Arif B. Ekici
Author: Matthias W. Beckmann
Author: Isabel dos Santos Silva
Author: Nichola Johnson
Author: Helen Warren
Author: Ian Tomlinson
Author: Michael J Kerin
Author: Nicola Miller
Author: Federick Marme
Author: Andreas Schneeweiss
Author: Christof Sohn
Author: Therese Truong
Author: Pierre Laurent-Puig
Author: Pierre Kerbrat
Author: Børge G. Nordestgaard
Author: Sune F. Nielsen
Author: Henrik Flyger
Author: Roger L. Milne
Author: Jose Ignacio Arias Perez
Author: Primitiva Menéndez
Author: Heiko Müller
Author: Volker Arndt
Author: Christa Stegmaier
Author: Peter Lichtner
Author: Magdalena Lochmann
Author: Christina Justenhoven
Author: Yon-Dschun Ko
Author: Taru A. Muranen
Author: Kristiina Aittomäki
Author: Carl Blomqvist
Author: Dario Greco
Author: Tuomas Heikkinen
Author: Hidemi Ito
Author: Hiroji Iwata
Author: Yasushi Yatabe
Author: Natalia N. Antonenkova
Author: Sara Margolin
Author: Vesa Kataja
Author: Veli-Matti Kosma
Author: Jaana M. Hartikainen
Author: Rosemary Balleine
Author: Chiu-Chen Tseng
Author: David Van Den Berg
Author: Daniel O. Stram
Author: Patrick Neven
Author: Anne-Sophie Dieudonné
Author: Karin Leunen
Author: Anja Rudolph
Author: Stefan Nickels
Author: Dieter Flesch-Janys
Author: Paolo Peterlongo
Author: Bernard Peissel
Author: Loris Bernard
Author: Janet E. Olson
Author: Xianshu Wang
Author: Kristen Stevens
Author: Gianluca Severi
Author: Laura Baglietto
Author: Catriona McLean
Author: Gerhard A. Coetzee
Author: Ye Feng
Author: Brian E. Henderson
Author: Fredrick Schumacher
Author: Natalia V. Bogdanova
Author: France Labrèche
Author: Martine Dumont
Author: Cheng Har Yip
Author: Nur Aishah Mohd Taib
Author: Ching-Yu Cheng
Author: Martha Shrubsole
Author: Jirong Long
Author: Katri Pylkäs
Author: Arja Jukkola-Vuorinen
Author: Saila Kauppila
Author: Julia A. Knight
Author: Gord Glendon
Author: Anna Marie Mulligan
Author: Robertus A. E. M. Tollenaar
Author: Caroline M. Seynaeve
Author: Mieke Kriege
Author: Maartje J. Hooning
Author: Ans M. W. van den Ouweland
Author: Carolien H. M. van Deurzen
Author: Wei Lu
Author: Yu-Tang Gao
Author: Hui Cai
Author: Sabapathy P. Balasubramanian
Author: Simon S. Cross
Author: Malcolm W. R. Reed
Author: Lisa Signorello
Author: Qiuyin Cai
Author: Mitul Shah
Author: Hui Miao
Author: Ching Wan Chan
Author: Kee Seng Chia
Author: Anna Jakubowska
Author: Katarzyna Jaworska
Author: Katarzyna Durda
Author: Chia-Ni Hsiung
Author: Pei-Ei Wu
Author: Jyh-Cherng Yu
Author: Alan Ashworth
Author: Michael Jones
Author: Daniel C. Tessier
Author: Anna González-Neira
Author: Guillermo Pita
Author: M. Rosario Alonso
Author: Daniel Vincent
Author: Francois Bacot
Author: Christine B. Ambrosone
Author: Elisa V. Bandera
Author: Esther M. John
Author: Gary K. Chen
Author: Jennifer J. Hu
Author: Jorge L. Rodriguez-Gil
Author: Leslie Bernstein
Author: Michael F. Press
Author: Regina G. Ziegler
Author: Robert M. Millikan
Author: Sandra L. Deming-Halverson
Author: Sarah Nyante
Author: Sue A. Ingles
Author: Quinten Waisfisz
Author: Helen Tsimiklis
Author: Enes Makalic
Author: Daniel Schmidt
Author: Minh Bui
Author: Lorna Gibson
Author: Bertram Müller-Myhsok
Author: Rita K. Schmutzler
Author: Rebecca Hein
Author: Norbert Dahmen
Author: Lars Beckmann
Author: Kirsimari Aaltonen
Author: Kamila Czene
Author: Astrid Irwanto
Author: Jianjun Liu
Author: Clare Turnbull
Author: Nazneen Rahman
Author: Hanne Meijers-Heijboer
Author: Andre G. Uitterlinden
Author: Fernando Rivadeneira
Author: Curtis Olswold
Author: Susan Slager
Author: Robert Pilarski
Author: Foluso Ademuyiwa
Author: Irene Konstantopoulou
Author: Nicholas G. Martin
Author: Grant W. Montgomery
Author: Dennis J. Slamon
Author: Claudia Rauh
Author: Michael P. Lux
Author: Sebastian M. Jud
Author: Thomas Bruning
Author: JoEllen Weaver
Author: Priyanka Sharma
Author: Harsh Pathak
Author: Will Tapper ORCID iD
Author: Sue Gerty
Author: Lorraine Durcan
Author: Dimitrios Trichopoulos
Author: Rosario Tumino
Author: Petra H. Peeters
Author: Rudolf Kaaks
Author: Daniele Campa
Author: Federico Canzian
Author: Elisabete Weiderpass
Author: Mattias Johansson
Author: Kay-Tee Khaw
Author: Ruth Travis
Author: Françoise Clavel-Chapelon
Author: Laurence N. Kolonel
Author: Constance Chen
Author: Andy Beck
Author: Susan E. Hankinson
Author: Christine D. Berg
Author: Robert N. Hoover
Author: Jolanta Lissowska
Author: Jonine D. Figueroa
Author: Daniel I. Chasman
Author: Mia M. Gaudet
Author: W. Ryan Diver
Author: Walter C. Willett
Author: David J. Hunter
Author: Jacques Simard
Author: Javier Benitez
Author: Alison M. Dunning
Author: Mark E. Sherman
Author: Georgia Chenevix-Trench
Author: Stephen J. Chanock
Author: Per Hall
Author: Paul D. P. Pharoah
Author: Celine Vachon
Author: Douglas F. Easton
Author: Christopher A. Haiman
Author: Peter Kraft

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