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; Nicholas Orr; 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, Nicholas Orr, GENICA Network

School of Medicine, Dentistry and Biomedical Sciences

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

81 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 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.

Original language	English
Pages (from-to)	1795-803
Number of pages	9
Journal	Cancer Research
Volume	72
Issue number	7
DOIs	https://doi.org/10.1158/0008-5472.CAN-11-3364
Publication status	Published - 01 Apr 2012

Keywords

Breast Neoplasms
Chromosome Mapping
Chromosomes, Human, Pair 19
Female
Genetic Loci
Genetic Predisposition to Disease
Humans
Receptor, ErbB-2
Receptors, Estrogen
Receptors, Progesterone
Risk
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

UN SDGs

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

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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

@article{b6bc3575a05146849fc4939a7eec09af,

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.",

keywords = "Breast Neoplasms, Chromosome Mapping, Chromosomes, Human, Pair 19, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Risk, Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't",

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 Nicholas Orr and {GENICA Network}",

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 Inc.",

number = "7",

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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, Orr, N & GENICA Network 2012, '19p13.1 is a triple-negative-specific breast cancer susceptibility locus', Cancer Research, vol. 72, no. 7, pp. 1795-803. 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, 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 - Orr, Nicholas

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.

KW - Breast Neoplasms

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 19

KW - Female

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Humans

KW - Receptor, ErbB-2

KW - Receptors, Estrogen

KW - Receptors, Progesterone

KW - Risk

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, N.I.H., Intramural

KW - Research Support, Non-U.S. Gov't

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

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

M3 - 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

Abstract

Keywords

UN SDGs

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