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

K. N. Stevens; Zachary Fredericksen; C. M. Vachon; X. Wang; Sara Margolin; Annika Lindblom; Heli Nevanlinna; D. Greco; K. Aittomaki; Carl Blomqvist; Jenny Chang-Claude; A. Vrieling; Dieter Flesch-Janys; H.-P. Sinn; Shan Wang-Gohrke; Stefan Nickels; Hiltrud Brauch; Y.-D. Ko; H.-P. Fischer; R. K. Schmutzler; Alfons Meindl; C. R. Bartram; Sarah Schott; Christoph Engel; A. K. Godwin; J. Weaver; H. B. Pathak; P. Sharma; Hermann Brenner; Heiko Mul̈ler; Volker Arndt; Christa Stegmaier; P. Miron; Drakoulis Yannoukakos; A. Stavropoulou; George Fountzilas; H. J. Gogas; Ruth Swann; Miriam Dwek; Annie Perkins; R. L. Milne; Javier Benitez; M. P. Zamora; J. I. A. Perez; S. E. Bojesen; S. F. Nielsen; B. G. Nordestgaard; Henrik Flyger; P. Guenel; T. Truong; Florence Menegaux; Emilie Cordina-Duverger; Barbara Burwinkel; F. Marme; Andreas Schneeweiss; Christof Sohn; E. Sawyer; I. Tomlinson; Michael J. Kerin; Julian Peto; N. Johnson; Olivia Fletcher; Isabel Dos Santos Silva; P. A. Fasching; Matthias W. Beckmann; A. Hartmann; A. B. Ekici; Artitaya Lophatananon; K. Muir; Puttisak Puttawibul; S. Wiangnon; M. K. Schmidt; Annegien Broeks; L. M. Braaf; E. H. Rosenberg; J. L. Hopper; Carmel Apicella; D. J. Park; M. C. Southey; A. J. Swerdlow; Alan Ashworth; N. Orr; M. J. Schoemaker; Hoda Anton-Culver; Argyrios Ziogas; Leslie Bernstein; C. C. Dur; C.-Y. Shen; J.-C. Yu; H.-M. Hsu; C.-N. Hsiung; Ute Hamann; T. Dunnebier; T. Rudiger; H. U. Ulmer; P. P. Pharoah; A. M. Dunning; M. K. Humphreys; Q. Wang; A. Cox; S. S. Cross; M. W. Reed; Per Hall; Kamila Czene; C. B. Ambrosone; F. Ademuyiwa; H. Hwang; D. M. Eccles; Montserrat Garcia-Closas; J. D. Figueroa; M. E. Sherman; Jolanta Lissowska; Peter Devilee; C. Seynaeve; Robert A. E. M. Tollenaar; M. J. Hooning; I. L. Andrulis; J. A. Knight; Gord Glendon; A. M. Mulligan; Robert Winqvist; Katri Pylkas; Arja Jukkola-Vuorinen; Mervi Grip; E. M. John; Alexander Miron; G. G. Alnaes; V. Kristensen; A.-L. Borresen-Dale; G. G. Giles; Laura Baglietto; C. A. McLean; Gianluca Severi; M. L. Kosel; V. S. Pankratz; Susan Slager; J. E. Olson; Paolo Radice; Paolo Peterlongo; Siranoush Manoukian; Monica Barile; D. Lambrechts; S. Hatse; A.-S. Dieudonne; M.-R. Christiaens; Georgia Chenevix-Trench; Jonathan Beesley; X. Chen; Arto Mannermaa; V.-M. Kosma; J. M. Hartikainen; Ylermi Soini; D. F. Easton; Fergus J. Couch

doi:10.13025/24805

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

K. N. Stevens
, Zachary Fredericksen
, C. M. Vachon
, X. Wang
, Sara Margolin
, Annika Lindblom
, Heli Nevanlinna
, D. Greco
, K. Aittomaki
, Carl Blomqvist
, Jenny Chang-Claude
, A. Vrieling
, Dieter Flesch-Janys
, H.-P. Sinn
, Shan Wang-Gohrke
, Stefan Nickels
, Hiltrud Brauch
, Y.-D. Ko
, H.-P. Fischer
, R. K. Schmutzler

Alfons Meindl, C. R. Bartram, Sarah Schott, Christoph Engel, A. K. Godwin, J. Weaver, H. B. Pathak, P. Sharma, Hermann Brenner, Heiko Mul̈ler, Volker Arndt, Christa Stegmaier, P. Miron, Drakoulis Yannoukakos, A. Stavropoulou, George Fountzilas, H. J. Gogas, Ruth Swann, Miriam Dwek, Annie Perkins, R. L. Milne, Javier Benitez, M. P. Zamora, J. I. A. Perez, S. E. Bojesen, S. F. Nielsen, B. G. Nordestgaard, Henrik Flyger, P. Guenel, T. Truong, Florence Menegaux, Emilie Cordina-Duverger, Barbara Burwinkel, F. Marme, Andreas Schneeweiss, Christof Sohn, E. Sawyer, I. Tomlinson, Michael J. Kerin, Julian Peto, N. Johnson, Olivia Fletcher, Isabel Dos Santos Silva, P. A. Fasching, Matthias W. Beckmann, A. Hartmann, A. B. Ekici, Artitaya Lophatananon, K. Muir, Puttisak Puttawibul, S. Wiangnon, M. K. Schmidt, Annegien Broeks, L. M. Braaf, E. H. Rosenberg, J. L. Hopper, Carmel Apicella, D. J. Park, M. C. Southey, A. J. Swerdlow, Alan Ashworth, N. Orr, M. J. Schoemaker, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, C. C. Dur, C.-Y. Shen, J.-C. Yu, H.-M. Hsu, C.-N. Hsiung, Ute Hamann, T. Dunnebier, T. Rudiger, H. U. Ulmer, P. P. Pharoah, A. M. Dunning, M. K. Humphreys, Q. Wang, A. Cox, S. S. Cross, M. W. Reed, Per Hall, Kamila Czene, C. B. Ambrosone, F. Ademuyiwa, H. Hwang, D. M. Eccles, Montserrat Garcia-Closas, J. D. Figueroa, M. E. Sherman, Jolanta Lissowska, Peter Devilee, C. Seynaeve, Robert A. E. M. Tollenaar, M. J. Hooning, I. L. Andrulis, J. A. Knight, Gord Glendon, A. M. Mulligan, Robert Winqvist, Katri Pylkas, Arja Jukkola-Vuorinen, Mervi Grip, E. M. John, Alexander Miron, G. G. Alnaes, V. Kristensen, A.-L. Borresen-Dale, G. G. Giles, Laura Baglietto, C. A. McLean, Gianluca Severi, M. L. Kosel, V. S. Pankratz, Susan Slager, J. E. Olson, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, D. Lambrechts, S. Hatse, A.-S. Dieudonne, M.-R. Christiaens, Georgia Chenevix-Trench, Jonathan Beesley, X. Chen, Arto Mannermaa, V.-M. Kosma, J. M. Hartikainen, Ylermi Soini, D. F. Easton, Fergus J. Couch

Mayo Clinic
Karolinska University Hospital
University of Helsinki
Helsinki University Central Hospital
German Cancer Research Center
University Medical Center Hamburg-Eppendorf
Ruprecht-Karls-University Heidelberg
Ulm University
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
University of Tübingen
Johanniter Krankenhaus
Medical Faculty of the University of Bonn
University Hospital Cologne
Klinikum Rechts der Isar
Heidelberg University
University of Leipzig
University of Kansas Medical Center
Fox Chase Cancer Center
University of Kansas Medical Center
Saarland Cancer Registry
Dana-Farber Cancer Institute
Institute of Biosciences and Applications
Aristotle University of Thessaloniki
University of Athens
University of Westminster
La Paz University Hospital
Hospital Monte Naranco
Gentofte University Hospital
National Institutes of Health (NIH)
Université Paris-Sud
King's College London
Wellcome Trust Centre for Human Genetics
Galway University Hospital
London School of Hygiene and Tropical Medicine
Divisions of Molecular Pathology and Cancer Therapeutics
McGill University
University Hospital Erlangen
University of Erlangen-Nuremberg
Warwick Medical School
Prince of Songkla University
Khon Kaen University
The Netherlands Cancer Institute
University of Melbourne
University of California
City of Hope National Med Center
Cancer Prevention Institute of California
Academia Sinica, Institute of Biomedical Sciences
Tri-Service General Hospital
Städtisches Klinikum Karlsruhe
University of Cambridge
University of Sheffield
Karolinska Institutet
Roswell Park Cancer Institute
University of Southampton, Faculty of Medicine
National Cancer Institute (NCI)
M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
Leiden University Medical Center
Erasmus MC
University of Toronto Faculty of Medicine
University of Toronto
Princess Margaret Hospital
Li Ka Shing Knowledge Institute
University of Oulu
University of Oslo
Faculty of Medicine
Cancer Council Victoria
Alfred Hospital
Fondazione IRCCS (Istituto di Ricovero e Cura A Carattere Scientifico)
IFOM - The FIRC Institute of Molecular Oncology
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan
Department of Experimental Oncology
VIB Center for the Biology of Disease
KU Leuven
KU Leuven– University Hospital Leuven
QIMR Berghofer Medical Research Institute
University of Eastern Finland

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

84 Citations (Scopus)

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 ERnegative 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.

Original language	English
Pages (from-to)	1795-1803
Number of pages	9
Journal	Cancer Research
Volume	72
Issue number	7
DOIs	https://doi.org/10.13025/24805 https://doi.org/10.1158/0008-5472.can-11-3364
Publication status	Published - 1 Apr 2012
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.13025/24805Licence: CC BY-NC-ND
10.1158/0008-5472.can-11-3364

Cite this

Stevens, K. N., Fredericksen, Z., Vachon, C. M., Wang, X., Margolin, S., Lindblom, A., Nevanlinna, H., Greco, D., Aittomaki, K., Blomqvist, C., Chang-Claude, J., Vrieling, A., Flesch-Janys, D., Sinn, H.-P., Wang-Gohrke, S., Nickels, S., Brauch, H., Ko, Y.-D., Fischer, H.-P., ... Couch, F. J. (2012). 19p13.1 Is a triple-negative-specific breast cancer susceptibility locus. Cancer Research, 72(7), 1795-1803. https://doi.org/10.13025/24805, https://doi.org/10.1158/0008-5472.can-11-3364

@article{d9916665f7ec406e8c9300fdc8ce508e,

title = "19p13.1 Is a triple-negative-specific breast cancer susceptibility locus",

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 ERnegative 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.",

author = "Stevens, \{K. N.\} and Zachary Fredericksen and Vachon, \{C. M.\} and X. Wang and Sara Margolin and Annika Lindblom and Heli Nevanlinna and D. Greco and K. Aittomaki and Carl Blomqvist and Jenny Chang-Claude and A. Vrieling and Dieter Flesch-Janys and H.-P. Sinn and Shan Wang-Gohrke and Stefan Nickels and Hiltrud Brauch and Y.-D. Ko and H.-P. Fischer and Schmutzler, \{R. K.\} and Alfons Meindl and Bartram, \{C. R.\} and Sarah Schott and Christoph Engel and Godwin, \{A. K.\} and J. Weaver and Pathak, \{H. B.\} and P. Sharma and Hermann Brenner and Heiko Mu{\"l}ler and Volker Arndt and Christa Stegmaier and P. Miron and Drakoulis Yannoukakos and A. Stavropoulou and George Fountzilas and Gogas, \{H. J.\} and Ruth Swann and Miriam Dwek and Annie Perkins and Milne, \{R. L.\} and Javier Benitez and Zamora, \{M. P.\} and Perez, \{J. I. A.\} and Bojesen, \{S. E.\} and Nielsen, \{S. F.\} and Nordestgaard, \{B. G.\} and Henrik Flyger and P. Guenel and T. Truong and Florence Menegaux and Emilie Cordina-Duverger and Barbara Burwinkel and F. Marme and Andreas Schneeweiss and Christof Sohn and E. Sawyer and I. Tomlinson and Kerin, \{Michael J.\} and Julian Peto and N. Johnson and Olivia Fletcher and \{Dos Santos Silva\}, Isabel and Fasching, \{P. A.\} and Beckmann, \{Matthias W.\} and A. Hartmann and Ekici, \{A. B.\} and Artitaya Lophatananon and K. Muir and Puttisak Puttawibul and S. Wiangnon and Schmidt, \{M. K.\} and Annegien Broeks and Braaf, \{L. M.\} and Rosenberg, \{E. H.\} and Hopper, \{J. L.\} and Carmel Apicella and Park, \{D. J.\} and Southey, \{M. C.\} and Swerdlow, \{A. J.\} and Alan Ashworth and N. Orr and Schoemaker, \{M. J.\} and Hoda Anton-Culver and Argyrios Ziogas and Leslie Bernstein and Dur, \{C. C.\} and C.-Y. Shen and J.-C. Yu and H.-M. Hsu and C.-N. Hsiung and Ute Hamann and T. Dunnebier and T. Rudiger and Ulmer, \{H. U.\} and Pharoah, \{P. P.\} and Dunning, \{A. M.\} and Humphreys, \{M. K.\} and Q. Wang and A. Cox and Cross, \{S. S.\} and Reed, \{M. W.\} and Per Hall and Kamila Czene and Ambrosone, \{C. B.\} and F. Ademuyiwa and H. Hwang and Eccles, \{D. M.\} and Montserrat Garcia-Closas and Figueroa, \{J. D.\} and Sherman, \{M. E.\} and Jolanta Lissowska and Peter Devilee and C. Seynaeve and Tollenaar, \{Robert A. E. M.\} and Hooning, \{M. J.\} and Andrulis, \{I. L.\} and Knight, \{J. A.\} and Gord Glendon and Mulligan, \{A. M.\} and Robert Winqvist and Katri Pylkas and Arja Jukkola-Vuorinen and Mervi Grip and John, \{E. M.\} and Alexander Miron and Alnaes, \{G. G.\} and V. Kristensen and A.-L. Borresen-Dale and Giles, \{G. G.\} and Laura Baglietto and McLean, \{C. A.\} and Gianluca Severi and Kosel, \{M. L.\} and Pankratz, \{V. S.\} and Susan Slager and Olson, \{J. E.\} and Paolo Radice and Paolo Peterlongo and Siranoush Manoukian and Monica Barile and D. Lambrechts and S. Hatse and A.-S. Dieudonne and M.-R. Christiaens and Georgia Chenevix-Trench and Jonathan Beesley and X. Chen and Arto Mannermaa and V.-M. Kosma and Hartikainen, \{J. M.\} and Ylermi Soini and Easton, \{D. F.\} and Couch, \{Fergus J.\}",

year = "2012",

month = apr,

day = "1",

doi = "10.13025/24805",

language = "English",

volume = "72",

pages = "1795--1803",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research Inc.",

number = "7",

}

Stevens, KN, Fredericksen, Z, Vachon, CM, Wang, X, Margolin, S, Lindblom, A, Nevanlinna, H, Greco, D, Aittomaki, K, Blomqvist, C, Chang-Claude, J, Vrieling, A, Flesch-Janys, D, Sinn, H-P, Wang-Gohrke, S, Nickels, S, Brauch, H, Ko, Y-D, Fischer, H-P, Schmutzler, RK, Meindl, A, Bartram, CR, Schott, S, Engel, C, Godwin, AK, Weaver, J, Pathak, HB, Sharma, P, Brenner, H, Mul̈ler, H, Arndt, V, Stegmaier, C, Miron, P, Yannoukakos, D, Stavropoulou, A, Fountzilas, G, Gogas, HJ, Swann, R, Dwek, M, Perkins, A, Milne, RL, Benitez, J, Zamora, MP, Perez, JIA, Bojesen, SE, Nielsen, SF, Nordestgaard, BG, Flyger, H, Guenel, P, Truong, T, Menegaux, F, Cordina-Duverger, E, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Sawyer, E, Tomlinson, I, Kerin, MJ, Peto, J, Johnson, N, Fletcher, O, Dos Santos Silva, I, Fasching, PA, Beckmann, MW, Hartmann, A, Ekici, AB, Lophatananon, A, Muir, K, Puttawibul, P, Wiangnon, S, Schmidt, MK, Broeks, A, Braaf, LM, Rosenberg, EH, Hopper, JL, Apicella, C, Park, DJ, Southey, MC, Swerdlow, AJ, Ashworth, A, Orr, N, Schoemaker, MJ, Anton-Culver, H, Ziogas, A, Bernstein, L, Dur, CC, Shen, C-Y, Yu, J-C, Hsu, H-M, Hsiung, C-N, Hamann, U, Dunnebier, T, Rudiger, T, Ulmer, HU, Pharoah, PP, Dunning, AM, Humphreys, MK, Wang, Q, Cox, A, Cross, SS, Reed, MW, Hall, P, Czene, K, Ambrosone, CB, Ademuyiwa, F, Hwang, H, Eccles, DM, Garcia-Closas, M, Figueroa, JD, Sherman, ME, Lissowska, J, Devilee, P, Seynaeve, C, Tollenaar, RAEM, Hooning, MJ, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, John, EM, Miron, A, Alnaes, GG, Kristensen, V, Borresen-Dale, A-L, Giles, GG, Baglietto, L, McLean, CA, Severi, G, Kosel, ML, Pankratz, VS, Slager, S, Olson, JE, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Lambrechts, D, Hatse, S, Dieudonne, A-S, Christiaens, M-R, Chenevix-Trench, G, Beesley, J, Chen, X, Mannermaa, A, Kosma, V-M, Hartikainen, JM, Soini, Y, Easton, DF & Couch, FJ 2012, '19p13.1 Is a triple-negative-specific breast cancer susceptibility locus', Cancer Research, vol. 72, no. 7, pp. 1795-1803. https://doi.org/10.13025/24805, https://doi.org/10.1158/0008-5472.can-11-3364

TY - JOUR

T1 - 19p13.1 Is a triple-negative-specific breast cancer susceptibility locus

AU - Stevens, K. N.

AU - Fredericksen, Zachary

AU - Vachon, C. M.

AU - Wang, X.

AU - Margolin, Sara

AU - Lindblom, Annika

AU - Nevanlinna, Heli

AU - Greco, D.

AU - Aittomaki, K.

AU - Blomqvist, Carl

AU - Chang-Claude, Jenny

AU - Vrieling, A.

AU - Flesch-Janys, Dieter

AU - Sinn, H.-P.

AU - Wang-Gohrke, Shan

AU - Nickels, Stefan

AU - Brauch, Hiltrud

AU - Ko, Y.-D.

AU - Fischer, H.-P.

AU - Schmutzler, R. K.

AU - Meindl, Alfons

AU - Bartram, C. R.

AU - Schott, Sarah

AU - Engel, Christoph

AU - Godwin, A. K.

AU - Weaver, J.

AU - Pathak, H. B.

AU - Sharma, P.

AU - Brenner, Hermann

AU - Mul̈ler, Heiko

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Miron, P.

AU - Yannoukakos, Drakoulis

AU - Stavropoulou, A.

AU - Fountzilas, George

AU - Gogas, H. J.

AU - Swann, Ruth

AU - Dwek, Miriam

AU - Perkins, Annie

AU - Milne, R. L.

AU - Benitez, Javier

AU - Zamora, M. P.

AU - Perez, J. I. A.

AU - Bojesen, S. E.

AU - Nielsen, S. F.

AU - Nordestgaard, B. G.

AU - Flyger, Henrik

AU - Guenel, P.

AU - Truong, T.

AU - Menegaux, Florence

AU - Cordina-Duverger, Emilie

AU - Burwinkel, Barbara

AU - Marme, F.

AU - Schneeweiss, Andreas

AU - Sohn, Christof

AU - Sawyer, E.

AU - Tomlinson, I.

AU - Kerin, Michael J.

AU - Peto, Julian

AU - Johnson, N.

AU - Fletcher, Olivia

AU - Dos Santos Silva, Isabel

AU - Fasching, P. A.

AU - Beckmann, Matthias W.

AU - Hartmann, A.

AU - Ekici, A. B.

AU - Lophatananon, Artitaya

AU - Muir, K.

AU - Puttawibul, Puttisak

AU - Wiangnon, S.

AU - Schmidt, M. K.

AU - Broeks, Annegien

AU - Braaf, L. M.

AU - Rosenberg, E. H.

AU - Hopper, J. L.

AU - Apicella, Carmel

AU - Park, D. J.

AU - Southey, M. C.

AU - Swerdlow, A. J.

AU - Ashworth, Alan

AU - Orr, N.

AU - Schoemaker, M. J.

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Bernstein, Leslie

AU - Dur, C. C.

AU - Shen, C.-Y.

AU - Yu, J.-C.

AU - Hsu, H.-M.

AU - Hsiung, C.-N.

AU - Hamann, Ute

AU - Dunnebier, T.

AU - Rudiger, T.

AU - Ulmer, H. U.

AU - Pharoah, P. P.

AU - Dunning, A. M.

AU - Humphreys, M. K.

AU - Wang, Q.

AU - Cox, A.

AU - Cross, S. S.

AU - Reed, M. W.

AU - Hall, Per

AU - Czene, Kamila

AU - Ambrosone, C. B.

AU - Ademuyiwa, F.

AU - Hwang, H.

AU - Eccles, D. M.

AU - Garcia-Closas, Montserrat

AU - Figueroa, J. D.

AU - Sherman, M. E.

AU - Lissowska, Jolanta

AU - Devilee, Peter

AU - Seynaeve, C.

AU - Tollenaar, Robert A. E. M.

AU - Hooning, M. J.

AU - Andrulis, I. L.

AU - Knight, J. A.

AU - Glendon, Gord

AU - Mulligan, A. M.

AU - Winqvist, Robert

AU - Pylkas, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - John, E. M.

AU - Miron, Alexander

AU - Alnaes, G. G.

AU - Kristensen, V.

AU - Borresen-Dale, A.-L.

AU - Giles, G. G.

AU - Baglietto, Laura

AU - McLean, C. A.

AU - Severi, Gianluca

AU - Kosel, M. L.

AU - Pankratz, V. S.

AU - Slager, Susan

AU - Olson, J. E.

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Barile, Monica

AU - Lambrechts, D.

AU - Hatse, S.

AU - Dieudonne, A.-S.

AU - Christiaens, M.-R.

AU - Chenevix-Trench, Georgia

AU - Beesley, Jonathan

AU - Chen, X.

AU - Mannermaa, Arto

AU - Kosma, V.-M.

AU - Hartikainen, J. M.

AU - Soini, Ylermi

AU - Easton, D. F.

AU - Couch, Fergus J.

PY - 2012/4/1

Y1 - 2012/4/1

N2 - 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 ERnegative 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.

AB - 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 ERnegative 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.

UR - http://hdl.handle.net/10379/14018

UR - https://www.scopus.com/pages/publications/84859375225

U2 - 10.13025/24805

DO - 10.13025/24805

M3 - Article

SN - 0008-5472

VL - 72

SP - 1795

EP - 1803

JO - Cancer Research

JF - Cancer Research

IS - 7

ER -

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

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