The University of Southampton
University of Southampton Institutional Repository

19p13.1 is a triple-negative-specific breast cancer susceptibility locus

19p13.1 is a triple-negative-specific breast cancer susceptibility locus
19p13.1 is a triple-negative-specific breast cancer susceptibility locus
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.
0008-5472
1795-1803
Stevens, K.N.
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Fredericksen, Z.
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Vachon, C.M.
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Wang, X.
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Margolin, S.
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Lindblom, A.
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Nevanlinna, H.
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Greco, D.
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Aittomaki, K.
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Blomqvist, C.
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Chang-Claude, J.
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Vrieling, A.
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Flesch-Janys, D.
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Sinn, H.-P.
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Fischer, H.-P.
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Schott, S.
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Engel, C.
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Godwin, A.K.
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Weaver, J.
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Pathak, H.B.
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Sharma, P.
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Muller, H.
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Arndt, V.
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Stegmaier, C.
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Miron, P.
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Yannoukakos, D.
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Stavropoulou, A.
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Fountzilas, G.
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Gogas, H. J.
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Swann, R.
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Dwek, M.
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Perkins, A.
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Milne, R. L.
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Benitez, J.
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Perez, J. I. A.
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Bojesen, S. E.
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Nielsen, S. F.
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Nordestgaard, B. G.
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Flyger, H.
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Guenel, P.
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Truong, T.
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Burwinkel, B.
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Sohn, C.
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Sawyer, E.
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Tomlinson, I.
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Johnson, N.
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Fletcher, O.
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dos Santos Silva, I.
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Fasching, P. A.
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Beckmann, M. W.
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Hartmann, A.
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Wiangnon, S.
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Vachon, C.M.
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Wang, X.
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Margolin, S.
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Lindblom, A.
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Aittomaki, K.
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Blomqvist, C.
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Vrieling, A.
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Flesch-Janys, D.
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Sinn, H.-P.
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Wang-Gohrke, S.
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Brauch, H.
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Sharma, P.
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Arndt, V.
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Stegmaier, C.
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Miron, P.
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Yannoukakos, D.
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Stavropoulou, A.
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Fountzilas, G.
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Gogas, H. J.
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Swann, R.
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Dwek, M.
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Perkins, A.
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Milne, R. L.
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Benitez, J.
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Zamora, M. P.
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Perez, J. I. A.
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Bojesen, S. E.
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Nielsen, S. F.
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Nordestgaard, B. G.
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Flyger, H.
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Guenel, P.
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Truong, T.
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Menegaux, F.
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Cordina-Duverger, E.
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Burwinkel, B.
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Marme, F.
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Schneeweiss, A.
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Sohn, C.
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Sawyer, E.
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Tomlinson, I.
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Kerin, M. J.
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Peto, J.
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Johnson, N.
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Fletcher, O.
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dos Santos Silva, I.
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Fasching, P. A.
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Beckmann, M. W.
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Czene, K.
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Ambrosone, C. B.
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Ademuyiwa, F.
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Hwang, H.
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Eccles, D. M.
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Garcia-Closas, M.
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Figueroa, J. D.
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Stevens, K.N., Fredericksen, Z. and Vachon, C.M. et al. (2012) 19p13.1 is a triple-negative-specific breast cancer susceptibility locus. Cancer Research, 72 (7), 1795-1803. (doi:10.1158/0008-5472.CAN-11-3364). (PMID:22331459)

Record type: Article

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.

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Accepted/In Press date: 19 January 2012
e-pub ahead of print date: 13 February 2012
Published date: 1 April 2012
Organisations: Cancer Sciences

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Local EPrints ID: 383030
URI: http://eprints.soton.ac.uk/id/eprint/383030
ISSN: 0008-5472
PURE UUID: 2efde8a0-9a11-45c4-9f71-4e9ffd2fa926
ORCID for D. M. Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 19 Oct 2015 09:38
Last modified: 15 Mar 2024 02:40

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Contributors

Author: K.N. Stevens
Author: Z. Fredericksen
Author: C.M. Vachon
Author: X. Wang
Author: S. Margolin
Author: A. Lindblom
Author: H. Nevanlinna
Author: D. Greco
Author: K. Aittomaki
Author: C. Blomqvist
Author: J. Chang-Claude
Author: A. Vrieling
Author: D. Flesch-Janys
Author: H.-P. Sinn
Author: S. Wang-Gohrke
Author: S. Nickels
Author: H. Brauch
Author: Y.-D. Ko
Author: H.-P. Fischer
Author: R.K. Schmutzler
Author: A. Meindl
Author: C.R. Bartram
Author: S. Schott
Author: C. Engel
Author: A.K. Godwin
Author: J. Weaver
Author: H.B. Pathak
Author: P. Sharma
Author: H. Brenner
Author: H. Muller
Author: V. Arndt
Author: C. Stegmaier
Author: P. Miron
Author: D. Yannoukakos
Author: A. Stavropoulou
Author: G. Fountzilas
Author: H. J. Gogas
Author: R. Swann
Author: M. Dwek
Author: A. Perkins
Author: R. L. Milne
Author: J. Benitez
Author: M. P. Zamora
Author: J. I. A. Perez
Author: S. E. Bojesen
Author: S. F. Nielsen
Author: B. G. Nordestgaard
Author: H. Flyger
Author: P. Guenel
Author: T. Truong
Author: F. Menegaux
Author: E. Cordina-Duverger
Author: B. Burwinkel
Author: F. Marme
Author: A. Schneeweiss
Author: C. Sohn
Author: E. Sawyer
Author: I. Tomlinson
Author: M. J. Kerin
Author: J. Peto
Author: N. Johnson
Author: O. Fletcher
Author: I. dos Santos Silva
Author: P. A. Fasching
Author: M. W. Beckmann
Author: A. Hartmann
Author: A. B. Ekici
Author: A. Lophatananon
Author: K. Muir
Author: P. Puttawibul
Author: S. Wiangnon
Author: M. K. Schmidt
Author: A. Broeks
Author: L. M. Braaf
Author: E. H. Rosenberg
Author: J. L. Hopper
Author: C. Apicella
Author: D. J. Park
Author: M. C. Southey
Author: A. J. Swerdlow
Author: A. Ashworth
Author: N. Orr
Author: M. J. Schoemaker
Author: H. Anton-Culver
Author: A. Ziogas
Author: L. Bernstein
Author: C. C. Dur
Author: C.-Y. Shen
Author: J.-C. Yu
Author: H.-M. Hsu
Author: C.-N. Hsiung
Author: U. Hamann
Author: T. Dunnebier
Author: T. Rudiger
Author: H. U. Ulmer
Author: P. P. Pharoah
Author: A. M. Dunning
Author: M. K. Humphreys
Author: Q. Wang
Author: A. Cox
Author: S. S. Cross
Author: M. W. Reed
Author: P. Hall
Author: K. Czene
Author: C. B. Ambrosone
Author: F. Ademuyiwa
Author: H. Hwang
Author: D. M. Eccles ORCID iD
Author: M. Garcia-Closas
Author: J. D. Figueroa
Author: M. E. Sherman
Author: J. Lissowska
Author: P. Devilee
Author: C. Seynaeve
Author: R. A. E. M. Tollenaar
Author: M. J. Hooning
Author: I. L. Andrulis
Author: J. A. Knight
Author: G. Glendon
Author: A. M. Mulligan
Author: R. Winqvist
Author: K. Pylkas
Author: A. Jukkola-Vuorinen
Author: M. Grip
Author: E. M. John
Author: A. Miron
Author: G. G. Alnaes
Author: V. Kristensen
Author: A.-L. Borresen-Dale
Author: G. G. Giles
Author: L. Baglietto
Author: C. A. McLean
Author: G. Severi
Author: M. L. Kosel
Author: V. S. Pankratz
Author: S. Slager
Author: J. E. Olson
Author: P. Radice
Author: P. Peterlongo
Author: S. Manoukian
Author: M. Barile
Author: D. Lambrechts
Author: S. Hatse
Author: A.-S. Dieudonne
Author: M.-R. Christiaens
Author: G. Chenevix-Trench
Author: J. Beesley
Author: X. Chen
Author: A. Mannermaa
Author: V.-M. Kosma
Author: J. M. Hartikainen
Author: Y. Soini
Author: D. F. Easton
Author: F. J. Couch

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