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

Kristen N. Stevens; Zachary Fredericksen; Celine M. Vachon; Xianshu Wang; Sara Margolin; Annika Lindblom; Heli Nevanlinna; Dario Greco; Kristiina Aittomak̈i; Carl Blomqvist; Jenny Chang-Claude; Alina Vrieling; Dieter Flesch-Janys; Hans Peter Sinn; Shan Wang-Gohrke; Stefan Nickels; Hiltrud Brauch; Yon Dschun Ko; Hans Peter Fischer; Rita K. Schmutzler; Alfons Meindl; Claus R. Bartram; Sarah Schott; Christoph Engel; Andrew K. Godwin; JoEllen Weaver; Harsh B. Pathak; Priyanka Sharma; Hermann Brenner; Heiko Mul̈ler; Volker Arndt; Christa Stegmaier; Penelope Miron; Drakoulis Yannoukakos; Alexandra Stavropoulou; George Fountzilas; Helen J. Gogas; Ruth Swann; Miriam Dwek; Annie Perkins; Roger L. Milne; Javier Benit́ez; Mariá Pilar Zamora; José Ignacio Arias Peŕez; Stig E. Bojesen; Sune F. Nielsen; Brøge G. Nordestgaard; Henrik Flyger; Pascal Gueńel; Theŕeśe Truong; Florence Menegaux; Emilie Cordina-Duverger; Barbara Burwinkel; Frederick Marme; Andreas Schneeweiss; Christof Sohn; Elinor Sawyer; Ian Tomlinson; Michael J. Kerin; Julian Peto; Nichola Johnson; Olivia Fletcher; Isabel Dos Santos Silva; Peter A. Fasching; Matthias W. Beckmann; Arndt Hartmann; Arif B. Ekici; Artitaya Lophatananon; Kenneth Muir; Puttisak Puttawibul; Surapon Wiangnon; Marjanka K. Schmidt; Annegien Broeks; Linde M. Braaf; Efraim H. Rosenberg; John L. Hopper; Carmel Apicella; Daniel J. Park; Melissa C. Southey; Anthony J. Swerdlow; Alan Ashworth; Orr Nicholas; Minouk J. Schoemaker; Hoda Anton-Culver; Argyrios Ziogas; Leslie Bernstein; Christina Clarke Dur; Chen Yang Shen; Jyh Cherng Yu; Huan Ming Hsu; Chia Ni Hsiung; Ute Hamann; Thomas Dun̈nebier; Thomas Rud̈iger; Hans Ulrich Ulmer; Paul P. Pharoah; Alison M. Dunning; Manjeet K. Humphreys; Qin Wang; Angela Cox; Simon S. Cross; Malcom W. Reed; Per Hall; Kamila Czene; Christine B. Ambrosone; Foluso Ademuyiwa; Helena Hwang; Diana M. Eccles; Montserrat Garcia-Closas; Jonine D. Figueroa; Mark E. Sherman; Jolanta Lissowska; Peter Devilee; Caroline Seynaeve; Rob A E M Tollenaar; Maartje J. Hooning; Irene L. Andrulis; Julia A. Knight; Gord Glendon; Anna Marie Mulligan; Robert Winqvist; Katri Pylkas̈; Arja Jukkola-Vuorinen; Mervi Grip; Esther M. John; Alexander Miron; Grethe Grenaker Alnsæ; Vessela Kristensen; Anne Lise Brøresen-Dale; Graham G. Giles; Laura Baglietto; Catriona A. McLean; Gianluca Severi; Matthew L. Kosel; V. S. Pankratz; Susan Slager; Janet E. Olson; Paolo Radice; Paolo Peterlongo; Siranoush Manoukian; Monica Barile; Diether Lambrechts; Sigrid Hatse; Anne Sophie Dieudonne; Marie Rose Christiaens; Georgia Chenevix-Trench; Jonathan Beesley; Xiaoqing Chen; Arto Mannermaa; Veli Matti Kosma; Jaana M. Hartikainen; Ylermi Soini; Douglas F. Easton; Fergus J. Couch

doi:10.1158/0008-5472.CAN-11-3364

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

Kristen N. Stevens, Zachary Fredericksen, Celine M. Vachon, Xianshu Wang, Sara Margolin, Annika Lindblom, Heli Nevanlinna, Dario Greco, Kristiina Aittomak̈i, Carl Blomqvist, Jenny Chang-Claude, Alina Vrieling, Dieter Flesch-Janys, Hans Peter Sinn, Shan Wang-Gohrke, Stefan Nickels, Hiltrud Brauch, Yon Dschun Ko, Hans Peter Fischer, Rita K. SchmutzlerAlfons Meindl, Claus R. Bartram, Sarah Schott, Christoph Engel, Andrew K. Godwin, JoEllen Weaver, Harsh B. Pathak, Priyanka Sharma, Hermann Brenner, Heiko Mul̈ler, Volker Arndt, Christa Stegmaier, Penelope Miron, Drakoulis Yannoukakos, Alexandra Stavropoulou, George Fountzilas, Helen J. Gogas, Ruth Swann, Miriam Dwek, Annie Perkins, Roger L. Milne, Javier Benit́ez, Mariá Pilar Zamora, José Ignacio Arias Peŕez, Stig E. Bojesen, Sune F. Nielsen, Brøge G. Nordestgaard, Henrik Flyger, Pascal Gueńel, Theŕeśe Truong, Florence Menegaux, Emilie Cordina-Duverger, Barbara Burwinkel, Frederick Marme, Andreas Schneeweiss, Christof Sohn, Elinor Sawyer, Ian Tomlinson, Michael J. Kerin, Julian Peto, Nichola Johnson, Olivia Fletcher, Isabel Dos Santos Silva, Peter A. Fasching, Matthias W. Beckmann, Arndt Hartmann, Arif B. Ekici, Artitaya Lophatananon, Kenneth Muir, Puttisak Puttawibul, Surapon Wiangnon, Marjanka K. Schmidt, Annegien Broeks, Linde M. Braaf, Efraim H. Rosenberg, John L. Hopper, Carmel Apicella, Daniel J. Park, Melissa C. Southey, Anthony J. Swerdlow, Alan Ashworth, Orr Nicholas, Minouk J. Schoemaker, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina Clarke Dur, Chen Yang Shen, Jyh Cherng Yu, Huan Ming Hsu, Chia Ni Hsiung, Ute Hamann, Thomas Dun̈nebier, Thomas Rud̈iger, Hans Ulrich Ulmer, Paul P. Pharoah, Alison M. Dunning, Manjeet K. Humphreys, Qin Wang, Angela Cox, Simon S. Cross, Malcom W. Reed, Per Hall, Kamila Czene, Christine B. Ambrosone, Foluso Ademuyiwa, Helena Hwang, Diana M. Eccles, Montserrat Garcia-Closas, Jonine D. Figueroa, Mark E. Sherman, Jolanta Lissowska, Peter Devilee, Caroline Seynaeve, Rob A E M Tollenaar, Maartje J. Hooning, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Anna Marie Mulligan, Robert Winqvist, Katri Pylkas̈, Arja Jukkola-Vuorinen, Mervi Grip, Esther M. John, Alexander Miron, Grethe Grenaker Alnsæ, Vessela Kristensen, Anne Lise Brøresen-Dale, Graham G. Giles, Laura Baglietto, Catriona A. McLean, Gianluca Severi, Matthew L. Kosel, V. S. Pankratz, Susan Slager, Janet E. Olson, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Diether Lambrechts, Sigrid Hatse, Anne Sophie Dieudonne, Marie Rose Christiaens, Georgia Chenevix-Trench, Jonathan Beesley, Xiaoqing Chen, Arto Mannermaa, Veli Matti Kosma, Jaana M. Hartikainen, Ylermi Soini, Douglas F. Easton, Fergus J. Couch

Research output: Contribution to journal › Article › peer-review

81 Scopus citations

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 (US)
Pages (from-to)	1795-1803
Number of pages	9
Journal	Cancer research
Volume	72
Issue number	7
DOIs	https://doi.org/10.1158/0008-5472.CAN-11-3364
State	Published - Apr 1 2012

ASJC Scopus subject areas

Oncology
Cancer Research

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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., Aittomak̈i, 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/10.1158/0008-5472.CAN-11-3364

Stevens, KN, Fredericksen, Z, Vachon, CM, Wang, X, Margolin, S, Lindblom, A, Nevanlinna, H, Greco, D, Aittomak̈i, K, Blomqvist, C, Chang-Claude, J, Vrieling, A, Flesch-Janys, D, Sinn, HP, Wang-Gohrke, S, Nickels, S, Brauch, H, Ko, YD, Fischer, HP, 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, Benit́ez, J, Zamora, MP, Peŕez, JIA, Bojesen, SE, Nielsen, SF, Nordestgaard, BG, Flyger, H, Gueńel, 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, Nicholas, O, Schoemaker, MJ, Anton-Culver, H, Ziogas, A, Bernstein, L, Dur, CC, Shen, CY, Yu, JC, Hsu, HM, Hsiung, CN, Hamann, U, Dun̈nebier, T, Rud̈iger, 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, Pylkas̈, K, Jukkola-Vuorinen, A, Grip, M, John, EM, Miron, A, Alnsæ, GG, Kristensen, V, Brøresen-Dale, AL, 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, AS, Christiaens, MR, Chenevix-Trench, G, Beesley, J, Chen, X, Mannermaa, A, Kosma, VM, 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/10.1158/0008-5472.CAN-11-3364

@article{a414667629e34988ae6ac8731198d781,

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, {Kristen N.} and Zachary Fredericksen and Vachon, {Celine M.} and Xianshu Wang and Sara Margolin and Annika Lindblom and Heli Nevanlinna and Dario Greco and Kristiina Aittoma{\"k}i and Carl Blomqvist and Jenny Chang-Claude and Alina Vrieling and Dieter Flesch-Janys and Sinn, {Hans Peter} and Shan Wang-Gohrke and Stefan Nickels and Hiltrud Brauch and Ko, {Yon Dschun} and Fischer, {Hans Peter} and Schmutzler, {Rita K.} and Alfons Meindl and Bartram, {Claus R.} and Sarah Schott and Christoph Engel and Godwin, {Andrew K.} and JoEllen Weaver and Pathak, {Harsh B.} and Priyanka Sharma and Hermann Brenner and Heiko Mu{\"l}ler and Volker Arndt and Christa Stegmaier and Penelope Miron and Drakoulis Yannoukakos and Alexandra Stavropoulou and George Fountzilas and Gogas, {Helen J.} and Ruth Swann and Miriam Dwek and Annie Perkins and Milne, {Roger L.} and Javier Beni{\'t}ez and Zamora, {Mari{\'a} Pilar} and Pe{\'r}ez, {Jos{\'e} Ignacio Arias} and Bojesen, {Stig E.} and Nielsen, {Sune F.} and Nordestgaard, {Br{\o}ge G.} and Henrik Flyger and Pascal Gue{\'n}el and The{\'r}e{\'s}e Truong and Florence Menegaux and Emilie Cordina-Duverger and Barbara Burwinkel and Frederick Marme and Andreas Schneeweiss and Christof Sohn and Elinor Sawyer and Ian Tomlinson and Kerin, {Michael J.} and Julian Peto and Nichola Johnson and Olivia Fletcher and {Dos Santos Silva}, Isabel and Fasching, {Peter A.} and Beckmann, {Matthias W.} and Arndt Hartmann and Ekici, {Arif B.} and Artitaya Lophatananon and Kenneth Muir and Puttisak Puttawibul and Surapon Wiangnon and Schmidt, {Marjanka K.} and Annegien Broeks and Braaf, {Linde M.} and Rosenberg, {Efraim H.} and Hopper, {John L.} and Carmel Apicella and Park, {Daniel J.} and Southey, {Melissa C.} and Swerdlow, {Anthony J.} and Alan Ashworth and Orr Nicholas and Schoemaker, {Minouk J.} and Hoda Anton-Culver and Argyrios Ziogas and Leslie Bernstein and Dur, {Christina Clarke} and Shen, {Chen Yang} and Yu, {Jyh Cherng} and Hsu, {Huan Ming} and Hsiung, {Chia Ni} and Ute Hamann and Thomas Du{\"n}nebier and Thomas Ru{\"d}iger and Ulmer, {Hans Ulrich} and Pharoah, {Paul P.} and Dunning, {Alison M.} and Humphreys, {Manjeet K.} and Qin Wang and Angela Cox and Cross, {Simon S.} and Reed, {Malcom W.} and Per Hall and Kamila Czene and Ambrosone, {Christine B.} and Foluso Ademuyiwa and Helena Hwang and Eccles, {Diana M.} and Montserrat Garcia-Closas and Figueroa, {Jonine D.} and Sherman, {Mark E.} and Jolanta Lissowska and Peter Devilee and Caroline Seynaeve and Tollenaar, {Rob A E M} and Hooning, {Maartje J.} and Andrulis, {Irene L.} and Knight, {Julia A.} and Gord Glendon and Mulligan, {Anna Marie} and Robert Winqvist and Katri Pylka{\"s} and Arja Jukkola-Vuorinen and Mervi Grip and John, {Esther M.} and Alexander Miron and Alns{\ae}, {Grethe Grenaker} and Vessela Kristensen and Br{\o}resen-Dale, {Anne Lise} and Giles, {Graham G.} and Laura Baglietto and McLean, {Catriona A.} and Gianluca Severi and Kosel, {Matthew L.} and Pankratz, {V. S.} and Susan Slager and Olson, {Janet E.} and Paolo Radice and Paolo Peterlongo and Siranoush Manoukian and Monica Barile and Diether Lambrechts and Sigrid Hatse and Dieudonne, {Anne Sophie} and Christiaens, {Marie Rose} and Georgia Chenevix-Trench and Jonathan Beesley and Xiaoqing Chen and Arto Mannermaa and Kosma, {Veli Matti} and Hartikainen, {Jaana M.} and Ylermi Soini and Easton, {Douglas F.} and Couch, {Fergus J.}",

year = "2012",

month = apr,

day = "1",

doi = "10.1158/0008-5472.CAN-11-3364",

language = "English (US)",

volume = "72",

pages = "1795--1803",

journal = "Cancer research",

issn = "0008-5472",

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

number = "7",

}

TY - JOUR

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

AU - Stevens, Kristen N.

AU - Fredericksen, Zachary

AU - Vachon, Celine M.

AU - Wang, Xianshu

AU - Margolin, Sara

AU - Lindblom, Annika

AU - Nevanlinna, Heli

AU - Greco, Dario

AU - Aittomak̈i, Kristiina

AU - Blomqvist, Carl

AU - Chang-Claude, Jenny

AU - Vrieling, Alina

AU - Flesch-Janys, Dieter

AU - Sinn, Hans Peter

AU - Wang-Gohrke, Shan

AU - Nickels, Stefan

AU - Brauch, Hiltrud

AU - Ko, Yon Dschun

AU - Fischer, Hans Peter

AU - Schmutzler, Rita K.

AU - Meindl, Alfons

AU - Bartram, Claus R.

AU - Schott, Sarah

AU - Engel, Christoph

AU - Godwin, Andrew K.

AU - Weaver, JoEllen

AU - Pathak, Harsh B.

AU - Sharma, Priyanka

AU - Brenner, Hermann

AU - Mul̈ler, Heiko

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Miron, Penelope

AU - Yannoukakos, Drakoulis

AU - Stavropoulou, Alexandra

AU - Fountzilas, George

AU - Gogas, Helen J.

AU - Swann, Ruth

AU - Dwek, Miriam

AU - Perkins, Annie

AU - Milne, Roger L.

AU - Benit́ez, Javier

AU - Zamora, Mariá Pilar

AU - Peŕez, José Ignacio Arias

AU - Bojesen, Stig E.

AU - Nielsen, Sune F.

AU - Nordestgaard, Brøge G.

AU - Flyger, Henrik

AU - Gueńel, Pascal

AU - Truong, Theŕeśe

AU - Menegaux, Florence

AU - Cordina-Duverger, Emilie

AU - Burwinkel, Barbara

AU - Marme, Frederick

AU - Schneeweiss, Andreas

AU - Sohn, Christof

AU - Sawyer, Elinor

AU - Tomlinson, Ian

AU - Kerin, Michael J.

AU - Peto, Julian

AU - Johnson, Nichola

AU - Fletcher, Olivia

AU - Dos Santos Silva, Isabel

AU - Fasching, Peter A.

AU - Beckmann, Matthias W.

AU - Hartmann, Arndt

AU - Ekici, Arif B.

AU - Lophatananon, Artitaya

AU - Muir, Kenneth

AU - Puttawibul, Puttisak

AU - Wiangnon, Surapon

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Braaf, Linde M.

AU - Rosenberg, Efraim H.

AU - Hopper, John L.

AU - Apicella, Carmel

AU - Park, Daniel J.

AU - Southey, Melissa C.

AU - Swerdlow, Anthony J.

AU - Ashworth, Alan

AU - Nicholas, Orr

AU - Schoemaker, Minouk J.

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Bernstein, Leslie

AU - Dur, Christina Clarke

AU - Shen, Chen Yang

AU - Yu, Jyh Cherng

AU - Hsu, Huan Ming

AU - Hsiung, Chia Ni

AU - Hamann, Ute

AU - Dun̈nebier, Thomas

AU - Rud̈iger, Thomas

AU - Ulmer, Hans Ulrich

AU - Pharoah, Paul P.

AU - Dunning, Alison M.

AU - Humphreys, Manjeet K.

AU - Wang, Qin

AU - Cox, Angela

AU - Cross, Simon S.

AU - Reed, Malcom W.

AU - Hall, Per

AU - Czene, Kamila

AU - Ambrosone, Christine B.

AU - Ademuyiwa, Foluso

AU - Hwang, Helena

AU - Eccles, Diana M.

AU - Garcia-Closas, Montserrat

AU - Figueroa, Jonine D.

AU - Sherman, Mark E.

AU - Lissowska, Jolanta

AU - Devilee, Peter

AU - Seynaeve, Caroline

AU - Tollenaar, Rob A E M

AU - Hooning, Maartje J.

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Glendon, Gord

AU - Mulligan, Anna Marie

AU - Winqvist, Robert

AU - Pylkas̈, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - John, Esther M.

AU - Miron, Alexander

AU - Alnsæ, Grethe Grenaker

AU - Kristensen, Vessela

AU - Brøresen-Dale, Anne Lise

AU - Giles, Graham G.

AU - Baglietto, Laura

AU - McLean, Catriona A.

AU - Severi, Gianluca

AU - Kosel, Matthew L.

AU - Pankratz, V. S.

AU - Slager, Susan

AU - Olson, Janet E.

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Barile, Monica

AU - Lambrechts, Diether

AU - Hatse, Sigrid

AU - Dieudonne, Anne Sophie

AU - Christiaens, Marie Rose

AU - Chenevix-Trench, Georgia

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - Mannermaa, Arto

AU - Kosma, Veli Matti

AU - Hartikainen, Jaana M.

AU - Soini, Ylermi

AU - Easton, Douglas 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://www.scopus.com/inward/record.url?scp=84859375225&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859375225&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-11-3364

DO - 10.1158/0008-5472.CAN-11-3364

M3 - Article

C2 - 22331459

AN - SCOPUS:84859375225

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

Abstract

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