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 Aittomäki; 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 Müller; 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 Benítez; María Pilar Zamora; José Ignacio Arias Pérez; Stig E Bojesen; Sune F Nielsen; Børge G Nordestgaard; Henrik Flyger; Pascal Guénel; Thérèse Truong; GENICA Network

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 Aittomäki, 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 Müller, 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 Benítez, María Pilar Zamora, José Ignacio Arias Pérez, Stig E Bojesen, Sune F Nielsen, Børge G Nordestgaard, Henrik Flyger, Pascal Guénel, Thérèse Truong, GENICA Network

75 Citationer (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 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.

Originalsprog	Engelsk
Tidsskrift	Cancer Research
Vol/bind	72
Udgave nummer	7
Sider (fra-til)	1795-803
Antal sider	9
ISSN	0008-5472
DOI	https://doi.org/10.1158/0008-5472.CAN-11-3364
Status	Udgivet - 1 apr. 2012

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10.1158/0008-5472.CAN-11-3364

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Stevens, K. N., Fredericksen, Z., Vachon, C. M., Wang, X., Margolin, S., Lindblom, A., Nevanlinna, H., Greco, D., Aittomäki, 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., ... GENICA Network (2012). 19p13.1 is a triple-negative-specific breast cancer susceptibility locus. Cancer Research, 72(7), 1795-803. 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, Aittomäki, 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, Müller, H, Arndt, V, Stegmaier, C, Miron, P, Yannoukakos, D, Stavropoulou, A, Fountzilas, G, Gogas, HJ, Swann, R, Dwek, M, Perkins, A, Milne, RL, Benítez, J, Zamora, MP, Pérez, JIA, Bojesen, SE, Nielsen, SF, Nordestgaard, BG, Flyger, H, Guénel, P, Truong, T & GENICA Network 2012, '19p13.1 is a triple-negative-specific breast cancer susceptibility locus', Cancer Research, bind 72, nr. 7, s. 1795-803. https://doi.org/10.1158/0008-5472.CAN-11-3364

@article{28481ffd0397406ea2c11724e5d5adcd,

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 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.",

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 Aittom{\"a}ki and Carl Blomqvist and Jenny Chang-Claude and Alina Vrieling and Dieter Flesch-Janys and Hans-Peter Sinn and Shan Wang-Gohrke and Stefan Nickels and Hiltrud Brauch and Yon-Dschun Ko and Hans-Peter Fischer 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 M{\"u}ller 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 Ben{\'i}tez and Zamora, {Mar{\'i}a Pilar} and P{\'e}rez, {Jos{\'e} Ignacio Arias} and Bojesen, {Stig E} and Nielsen, {Sune F} and Nordestgaard, {B{\o}rge G} and Henrik Flyger and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and B{\o}rge Nordestgaard",

note = "{\textcopyright}2012 AACR.",

year = "2012",

month = apr,

day = "1",

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

language = "English",

volume = "72",

pages = "1795--803",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research",

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 - Aittomäki, 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 - Müller, 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 - Benítez, Javier

AU - Zamora, María Pilar

AU - Pérez, José Ignacio Arias

AU - Bojesen, Stig E

AU - Nielsen, Sune F

AU - Nordestgaard, Børge G

AU - Flyger, Henrik

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - GENICA Network

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 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.

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 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.

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

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

M3 - Journal article

C2 - 22331459

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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