A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

Antonis C. Antoniou; Xianshu Wang; Zachary S. Fredericksen; Lesley McGuffog; Robert Tarrell; Olga M. Sinilnikova; Sue Healey; Jonathan Morrison; Christiana Kartsonaki; Timothy Lesnick; Maya Ghoussaini; Daniel Barrowdale; Susan Peock; Margaret Cook; Clare Oliver; Debra Frost; Diana Eccles; D. Gareth Evans; Ros Eeles; Louise Izatt; Carol Chu; Fiona Douglas; Joan Paterson; Dominique Stoppa-Lyonnet; Claude Houdayer; Sylvie Mazoyer; Sophie Giraud; Christine Lasset; Audrey Remenieras; Olivier Caron; Agnès Hardouin; Pascaline Berthet; Frans B.L. Hogervorst; Matti A. Rookus; Agnes Jager; Ans Van Den Ouweland; Nicoline Hoogerbrugge; Rob B. Van Der Luijt; Hanne Meijers-Heijboer; Encarna B. G'mez García; Peter Devilee; Maaike P.G. Vreeswijk; Jan Lubinski; Anna Jakubowska; Jacek Gronwald; Tomasz Huzarski; Tomasz Byrski; Bohdan G'rski; Cezary Cybulski; Amanda B. Spurdle; Helene Holland; David E. Goldgar; Esther M. John; John L. Hopper; Melissa Southey; Saundra S. Buys; Mary B. Daly; Mary Beth Terry; Rita K. Schmutzler; Barbara Wappenschmidt; Christoph Engel; Alfons Meindl; Sabine Preisler-Adams; Norbert Arnold; Dieter Niederacher; Christian Sutter; Susan M. Domchek; Katherine L. Nathanson; Timothy Rebbeck; Joanne L. Blum; Marion Piedmonte; Gustavo C. Rodriguez; Katie Wakeley; John F. Boggess; Jack Basil; Stephanie V. Blank; Eitan Friedman; Bella Kaufman; Yael Laitman; Roni Milgrom; Irene L. Andrulis; Gord Glendon; Hilmi Ozcelik; Tomas Kirchhoff; Joseph Vijai; Mia M. Gaudet; David Altshuler; Candace Guiducci; Niklas Loman; Katja Harbst; Johanna Rantala; Hans Ehrencrona; Anne Marie Gerdes; Mads Thomassen; Lone Sunde; Paolo Peterlongo; Siranoush Manoukian; Bernardo Bonanni; Alessandra Viel; Paolo Radice; Trinidad Caldes; Miguel De La Hoya; Christian F. Singer; Anneliese Fink-Retter; Mark H. Greene; Phuong L. Mai; Jennifer T. Loud; Lucia Guidugli; Noralane M. Lindor; Thomas V.O. Hansen; Finn C. Nielsen; Ignacio Blanco; Conxi Lazaro; Judy Garber; Susan J. Ramus; Simon A. Gayther; Catherine Phelan; Stephen Narod; Csilla I. Szabo; Javier Benitez; Ana Osorio; Heli Nevanlinna; Tuomas Heikkinen; Maria A. Caligo; Mary S. Beattie; Ute Hamann; Andrew K. Godwin; Marco Montagna; Cinzia Casella; Susan L. Neuhausen; Beth Y. Karlan; Nadine Tung; Amanda E. Toland; Jeffrey Weitzel; Olofunmilayo Olopade; Jacques Simard; Penny Soucy; Wendy S. Rubinstein; Adalgeir Arason; Gad Rennert; Nicholas G. Martin; Grant W. Montgomery; Jenny Chang-Claude; Dieter Flesch-Janys; Hiltrud Brauch; Gianluca Severi; Laura Baglietto; Angela Cox; Simon S. Cross; Penelope Miron; Sue M. Gerty; William Tapper; Drakoulis Yannoukakos; George Fountzilas; Peter A. Fasching; Matthias W. Beckmann; Isabel Dos Santos Silva; Julian Peto; Diether Lambrechts; Robert Paridaens; Thomas Rüdiger; Asta Försti; Robert Winqvist; Katri Pylkäs; Robert B. Diasio; Adam M. Lee; Jeanette Eckel-Passow; Celine Vachon; Fiona Blows; Kristy Driver; Alison Dunning; Paul P.D. Pharoah; Kenneth Offit; V. Shane Pankratz; Hakon Hakonarson; Georgia Chenevix-Trench; Douglas F. Easton; Fergus J. Couch

doi:10.1038/ng.669

A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

Antonis C. Antoniou
, Xianshu Wang
, Zachary S. Fredericksen
, Lesley McGuffog
, Robert Tarrell
, Olga M. Sinilnikova
, Sue Healey
, Jonathan Morrison
, Christiana Kartsonaki
, Timothy Lesnick
, Maya Ghoussaini
, Daniel Barrowdale
, Susan Peock
, Margaret Cook
, Clare Oliver
, Debra Frost
, Diana Eccles
, D. Gareth Evans
, Ros Eeles
, Louise Izatt

Carol Chu, Fiona Douglas, Joan Paterson, Dominique Stoppa-Lyonnet, Claude Houdayer, Sylvie Mazoyer, Sophie Giraud, Christine Lasset, Audrey Remenieras, Olivier Caron, Agnès Hardouin, Pascaline Berthet, Frans B.L. Hogervorst, Matti A. Rookus, Agnes Jager, Ans Van Den Ouweland, Nicoline Hoogerbrugge, Rob B. Van Der Luijt, Hanne Meijers-Heijboer, Encarna B. G'mez García, Peter Devilee, Maaike P.G. Vreeswijk, Jan Lubinski, Anna Jakubowska, Jacek Gronwald, Tomasz Huzarski, Tomasz Byrski, Bohdan G'rski, Cezary Cybulski, Amanda B. Spurdle, Helene Holland, David E. Goldgar, Esther M. John, John L. Hopper, Melissa Southey, Saundra S. Buys, Mary B. Daly, Mary Beth Terry, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Sabine Preisler-Adams, Norbert Arnold, Dieter Niederacher, Christian Sutter, Susan M. Domchek, Katherine L. Nathanson, Timothy Rebbeck, Joanne L. Blum, Marion Piedmonte, Gustavo C. Rodriguez, Katie Wakeley, John F. Boggess, Jack Basil, Stephanie V. Blank, Eitan Friedman, Bella Kaufman, Yael Laitman, Roni Milgrom, Irene L. Andrulis, Gord Glendon, Hilmi Ozcelik, Tomas Kirchhoff, Joseph Vijai, Mia M. Gaudet, David Altshuler, Candace Guiducci, Niklas Loman, Katja Harbst, Johanna Rantala, Hans Ehrencrona, Anne Marie Gerdes, Mads Thomassen, Lone Sunde, Paolo Peterlongo, Siranoush Manoukian, Bernardo Bonanni, Alessandra Viel, Paolo Radice, Trinidad Caldes, Miguel De La Hoya, Christian F. Singer, Anneliese Fink-Retter, Mark H. Greene, Phuong L. Mai, Jennifer T. Loud, Lucia Guidugli, Noralane M. Lindor, Thomas V.O. Hansen, Finn C. Nielsen, Ignacio Blanco, Conxi Lazaro, Judy Garber, Susan J. Ramus, Simon A. Gayther, Catherine Phelan, Stephen Narod, Csilla I. Szabo, Javier Benitez, Ana Osorio, Heli Nevanlinna, Tuomas Heikkinen, Maria A. Caligo, Mary S. Beattie, Ute Hamann, Andrew K. Godwin, Marco Montagna, Cinzia Casella, Susan L. Neuhausen, Beth Y. Karlan, Nadine Tung, Amanda E. Toland, Jeffrey Weitzel, Olofunmilayo Olopade, Jacques Simard, Penny Soucy, Wendy S. Rubinstein, Adalgeir Arason, Gad Rennert, Nicholas G. Martin, Grant W. Montgomery, Jenny Chang-Claude, Dieter Flesch-Janys, Hiltrud Brauch, Gianluca Severi, Laura Baglietto, Angela Cox, Simon S. Cross, Penelope Miron, Sue M. Gerty, William Tapper, Drakoulis Yannoukakos, George Fountzilas, Peter A. Fasching, Matthias W. Beckmann, Isabel Dos Santos Silva, Julian Peto, Diether Lambrechts, Robert Paridaens, Thomas Rüdiger, Asta Försti, Robert Winqvist, Katri Pylkäs, Robert B. Diasio, Adam M. Lee, Jeanette Eckel-Passow, Celine Vachon, Fiona Blows, Kristy Driver, Alison Dunning, Paul P.D. Pharoah, Kenneth Offit, V. Shane Pankratz, Hakon Hakonarson, Georgia Chenevix-Trench, Douglas F. Easton, Fergus J. Couch

University of Cambridge
Mayo Clinic
Centre de Recherche en Cancérologie de Lyon
Université de Lyon
Queensland Institute of Medical Research
University Hospital Southampton NHS Foundation Trust
Manchester University NHS Foundation Trust
Royal Marsden NHS Foundation Trust
Guy's and St Thomas' NHS Foundation Trust
Yorkshire Regional Genetics Service
Newcastle upon Tyne Hospitals NHS Foundation Trust
Cambridge University Hospitals NHS Foundation Trust
Institut national de la santé et de la recherche médicale
Universite Claude Bernard Lyon 1
Centre Léon Bérard
Université Paris-Sud
Georges François Leclerc Cancer Center
Netherlands Cancer Institute
Erasmus University Rotterdam
Radboud University Nijmegen
Utrecht University
VU University Medical Center
Maastricht University
Leiden University
Pomeranian Medical University in Szczecin
University of Utah
Stanford University
University of Melbourne
Columbia University
University of Cologne
Leipzig University
Technical University of Munich
University of Münster
Kiel University
Heinrich Heine University Düsseldorf
Heidelberg University
University of Pennsylvania
Baylor Health Care System
Roswell Park Cancer Institute
NorthShore University HealthSystem
Tufts University
University of North Carolina at Chapel Hill
St. Elizabeth Medical Center, Edgewood
New York University
The Gertner Institute
Sheba Medical Center at Tel Hashomer
Cancer Care Ontario
University of Toronto
Memorial Hospital
Memorial Sloan-Kettering Cancer Center
Yeshiva University
Massachusetts Institute of Technology
Lund University
Karolinska Institutet
Uppsala University
University of Copenhagen
University of Southern Denmark
Aarhus University
Fondazione IRCCS Istituto Nazionale dei Tumori
FIRC Institute of Molecular Oncology
IRCCS Istituto Europeo di Oncologia - Milano
IRCCS Centro di Riferimento Oncologico - Aviano PN
Hospital Clínico San Carlos de Madrid
Medical University of Vienna
National Institutes of Health
Institute Catala Oncologia
Dana-Farber Cancer Institute
GENICA
University College London
University of South Florida
MOD SQUAD
Biomedical Network on Rare Diseases (CIBERER)
Helsinki University Hospital
SWE-BRCA
University of Pisa
University of California at San Francisco
German Cancer Research Center
Fox Chase Cancer Center
IRCCS Istituto Oncologico Veneto - Padova
City of Hope National Medical Center
Division of Gynecologic Oncology
University of California at Los Angeles
Beth Israel Deaconess Medical Center
Ohio State University
University of Chicago
Université Laval
Landspitali University Hospital
Technion-Israel Institute of Technology
University of Hamburg
Robert Bosch Foundation
University of Tübingen
Cancer Council Victoria
University of Sheffield
Demokritos National Centre for Scientific Research
Aristotle University of Thessaloniki
Hellenic Cooperative Oncology Group
Friedrich-Alexander University Erlangen-Nürnberg
London School of Hygiene and Tropical Medicine
Flanders Institute for Biotechnology
KU Leuven
Städtischen Klinikum Karlsruhe
University of Oulu
HEBON
Peter Maccallum Cancer Centre
The Children's Hospital of Philadelphia

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

277 Scopus citations

Abstract

Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P trend = 2.3 × 10 ⁹ to P trend = 3.9 × 10 ⁷), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (P_trend = 1 × 10 ⁷ to P trend = 8 × 10 ⁵; rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P trend = 1.1 × 10 ⁷).

Original language	English
Pages (from-to)	885-892
Number of pages	8
Journal	Nature Genetics
Volume	42
Issue number	10
DOIs	https://doi.org/10.1038/ng.669
State	Published - Sep 2010

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Adult
BRCA1 Protein/genetics
Breast Neoplasms/genetics
Case-Control Studies
Chromosomes, Human, Pair 19/genetics
Female
Genetic Predisposition to Disease
Genotype
Humans
Mutation/genetics
Polymorphism, Single Nucleotide/genetics
Receptor, ErbB-2/genetics
Receptors, Estrogen/genetics
Receptors, Progesterone/genetics

Access to Document

10.1038/ng.669

Cite this

Antoniou, A. C., Wang, X., Fredericksen, Z. S., McGuffog, L., Tarrell, R., Sinilnikova, O. M., Healey, S., Morrison, J., Kartsonaki, C., Lesnick, T., Ghoussaini, M., Barrowdale, D., Peock, S., Cook, M., Oliver, C., Frost, D., Eccles, D., Evans, D. G., Eeles, R., ... Couch, F. J. (2010). A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nature Genetics, 42(10), 885-892. https://doi.org/10.1038/ng.669

@article{f9f9bcc3c5f0490995379cefb9bf9068,

title = "A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population",

abstract = "Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P trend = 2.3 × 10 9 to P trend = 3.9 × 10 7), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95\% CI 1.17-1.35; rs2363956 HR = 0.84, 95\% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95\% CI 0.75-0.92, P trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95\% CI 1.01-1.14, P trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 × 10 7 to P trend = 8 × 10 5; rs2363956 per-allele OR = 0.80, 95\% CI 0.74-0.87, P trend = 1.1 × 10 7).",

keywords = "Adult, BRCA1 Protein/genetics, Breast Neoplasms/genetics, Case-Control Studies, Chromosomes, Human, Pair 19/genetics, Female, Genetic Predisposition to Disease, Genotype, Humans, Mutation/genetics, Polymorphism, Single Nucleotide/genetics, Receptor, ErbB-2/genetics, Receptors, Estrogen/genetics, Receptors, Progesterone/genetics",

author = "Antoniou, \{Antonis C.\} and Xianshu Wang and Fredericksen, \{Zachary S.\} and Lesley McGuffog and Robert Tarrell and Sinilnikova, \{Olga M.\} and Sue Healey and Jonathan Morrison and Christiana Kartsonaki and Timothy Lesnick and Maya Ghoussaini and Daniel Barrowdale and Susan Peock and Margaret Cook and Clare Oliver and Debra Frost and Diana Eccles and Evans, \{D. Gareth\} and Ros Eeles and Louise Izatt and Carol Chu and Fiona Douglas and Joan Paterson and Dominique Stoppa-Lyonnet and Claude Houdayer and Sylvie Mazoyer and Sophie Giraud and Christine Lasset and Audrey Remenieras and Olivier Caron and Agn{\`e}s Hardouin and Pascaline Berthet and Hogervorst, \{Frans B.L.\} and Rookus, \{Matti A.\} and Agnes Jager and \{Van Den Ouweland\}, Ans and Nicoline Hoogerbrugge and \{Van Der Luijt\}, \{Rob B.\} and Hanne Meijers-Heijboer and \{G'mez Garc{\'i}a\}, \{Encarna B.\} and Peter Devilee and Vreeswijk, \{Maaike P.G.\} and Jan Lubinski and Anna Jakubowska and Jacek Gronwald and Tomasz Huzarski and Tomasz Byrski and Bohdan G'rski and Cezary Cybulski and Spurdle, \{Amanda B.\} and Helene Holland and Goldgar, \{David E.\} and John, \{Esther M.\} and Hopper, \{John L.\} and Melissa Southey and Buys, \{Saundra S.\} and Daly, \{Mary B.\} and Terry, \{Mary Beth\} and Schmutzler, \{Rita K.\} and Barbara Wappenschmidt and Christoph Engel and Alfons Meindl and Sabine Preisler-Adams and Norbert Arnold and Dieter Niederacher and Christian Sutter and Domchek, \{Susan M.\} and Nathanson, \{Katherine L.\} and Timothy Rebbeck and Blum, \{Joanne L.\} and Marion Piedmonte and Rodriguez, \{Gustavo C.\} and Katie Wakeley and Boggess, \{John F.\} and Jack Basil and Blank, \{Stephanie V.\} and Eitan Friedman and Bella Kaufman and Yael Laitman and Roni Milgrom and Andrulis, \{Irene L.\} and Gord Glendon and Hilmi Ozcelik and Tomas Kirchhoff and Joseph Vijai and Gaudet, \{Mia M.\} and David Altshuler and Candace Guiducci and Niklas Loman and Katja Harbst and Johanna Rantala and Hans Ehrencrona and Gerdes, \{Anne Marie\} and Mads Thomassen and Lone Sunde and Paolo Peterlongo and Siranoush Manoukian and Bernardo Bonanni and Alessandra Viel and Paolo Radice and Trinidad Caldes and \{De La Hoya\}, Miguel and Singer, \{Christian F.\} and Anneliese Fink-Retter and Greene, \{Mark H.\} and Mai, \{Phuong L.\} and Loud, \{Jennifer T.\} and Lucia Guidugli and Lindor, \{Noralane M.\} and Hansen, \{Thomas V.O.\} and Nielsen, \{Finn C.\} and Ignacio Blanco and Conxi Lazaro and Judy Garber and Ramus, \{Susan J.\} and Gayther, \{Simon A.\} and Catherine Phelan and Stephen Narod and Szabo, \{Csilla I.\} and Javier Benitez and Ana Osorio and Heli Nevanlinna and Tuomas Heikkinen and Caligo, \{Maria A.\} and Beattie, \{Mary S.\} and Ute Hamann and Godwin, \{Andrew K.\} and Marco Montagna and Cinzia Casella and Neuhausen, \{Susan L.\} and Karlan, \{Beth Y.\} and Nadine Tung and Toland, \{Amanda E.\} and Jeffrey Weitzel and Olofunmilayo Olopade and Jacques Simard and Penny Soucy and Rubinstein, \{Wendy S.\} and Adalgeir Arason and Gad Rennert and Martin, \{Nicholas G.\} and Montgomery, \{Grant W.\} and Jenny Chang-Claude and Dieter Flesch-Janys and Hiltrud Brauch and Gianluca Severi and Laura Baglietto and Angela Cox and Cross, \{Simon S.\} and Penelope Miron and Gerty, \{Sue M.\} and William Tapper and Drakoulis Yannoukakos and George Fountzilas and Fasching, \{Peter A.\} and Beckmann, \{Matthias W.\} and \{Dos Santos Silva\}, Isabel and Julian Peto and Diether Lambrechts and Robert Paridaens and Thomas R{\"u}diger and Asta F{\"o}rsti and Robert Winqvist and Katri Pylk{\"a}s and Diasio, \{Robert B.\} and Lee, \{Adam M.\} and Jeanette Eckel-Passow and Celine Vachon and Fiona Blows and Kristy Driver and Alison Dunning and Pharoah, \{Paul P.D.\} and Kenneth Offit and Pankratz, \{V. Shane\} and Hakon Hakonarson and Georgia Chenevix-Trench and Easton, \{Douglas F.\} and Couch, \{Fergus J.\}",

year = "2010",

month = sep,

doi = "10.1038/ng.669",

language = "English",

volume = "42",

pages = "885--892",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

}

Antoniou, AC, Wang, X, Fredericksen, ZS, McGuffog, L, Tarrell, R, Sinilnikova, OM, Healey, S, Morrison, J, Kartsonaki, C, Lesnick, T, Ghoussaini, M, Barrowdale, D, Peock, S, Cook, M, Oliver, C, Frost, D, Eccles, D, Evans, DG, Eeles, R, Izatt, L, Chu, C, Douglas, F, Paterson, J, Stoppa-Lyonnet, D, Houdayer, C, Mazoyer, S, Giraud, S, Lasset, C, Remenieras, A, Caron, O, Hardouin, A, Berthet, P, Hogervorst, FBL, Rookus, MA, Jager, A, Van Den Ouweland, A, Hoogerbrugge, N, Van Der Luijt, RB, Meijers-Heijboer, H, G'mez García, EB, Devilee, P, Vreeswijk, MPG, Lubinski, J, Jakubowska, A, Gronwald, J, Huzarski, T, Byrski, T, G'rski, B, Cybulski, C, Spurdle, AB, Holland, H, Goldgar, DE, John, EM, Hopper, JL, Southey, M, Buys, SS, Daly, MB, Terry, MB, Schmutzler, RK, Wappenschmidt, B, Engel, C, Meindl, A, Preisler-Adams, S, Arnold, N, Niederacher, D, Sutter, C, Domchek, SM, Nathanson, KL, Rebbeck, T, Blum, JL, Piedmonte, M, Rodriguez, GC, Wakeley, K, Boggess, JF, Basil, J, Blank, SV, Friedman, E, Kaufman, B, Laitman, Y, Milgrom, R, Andrulis, IL, Glendon, G, Ozcelik, H, Kirchhoff, T, Vijai, J, Gaudet, MM, Altshuler, D, Guiducci, C, Loman, N, Harbst, K, Rantala, J, Ehrencrona, H, Gerdes, AM, Thomassen, M, Sunde, L, Peterlongo, P, Manoukian, S, Bonanni, B, Viel, A, Radice, P, Caldes, T, De La Hoya, M, Singer, CF, Fink-Retter, A, Greene, MH, Mai, PL, Loud, JT, Guidugli, L, Lindor, NM, Hansen, TVO, Nielsen, FC, Blanco, I, Lazaro, C, Garber, J, Ramus, SJ, Gayther, SA, Phelan, C, Narod, S, Szabo, CI, Benitez, J, Osorio, A, Nevanlinna, H, Heikkinen, T, Caligo, MA, Beattie, MS, Hamann, U, Godwin, AK, Montagna, M, Casella, C, Neuhausen, SL, Karlan, BY, Tung, N, Toland, AE, Weitzel, J, Olopade, O, Simard, J, Soucy, P, Rubinstein, WS, Arason, A, Rennert, G, Martin, NG, Montgomery, GW, Chang-Claude, J, Flesch-Janys, D, Brauch, H, Severi, G, Baglietto, L, Cox, A, Cross, SS, Miron, P, Gerty, SM, Tapper, W, Yannoukakos, D, Fountzilas, G, Fasching, PA, Beckmann, MW, Dos Santos Silva, I, Peto, J, Lambrechts, D, Paridaens, R, Rüdiger, T, Försti, A, Winqvist, R, Pylkäs, K, Diasio, RB, Lee, AM, Eckel-Passow, J, Vachon, C, Blows, F, Driver, K, Dunning, A, Pharoah, PPD, Offit, K, Pankratz, VS, Hakonarson, H, Chenevix-Trench, G, Easton, DF & Couch, FJ 2010, 'A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population', Nature Genetics, vol. 42, no. 10, pp. 885-892. https://doi.org/10.1038/ng.669

TY - JOUR

T1 - A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

AU - Antoniou, Antonis C.

AU - Wang, Xianshu

AU - Fredericksen, Zachary S.

AU - McGuffog, Lesley

AU - Tarrell, Robert

AU - Sinilnikova, Olga M.

AU - Healey, Sue

AU - Morrison, Jonathan

AU - Kartsonaki, Christiana

AU - Lesnick, Timothy

AU - Ghoussaini, Maya

AU - Barrowdale, Daniel

AU - Peock, Susan

AU - Cook, Margaret

AU - Oliver, Clare

AU - Frost, Debra

AU - Eccles, Diana

AU - Evans, D. Gareth

AU - Eeles, Ros

AU - Izatt, Louise

AU - Chu, Carol

AU - Douglas, Fiona

AU - Paterson, Joan

AU - Stoppa-Lyonnet, Dominique

AU - Houdayer, Claude

AU - Mazoyer, Sylvie

AU - Giraud, Sophie

AU - Lasset, Christine

AU - Remenieras, Audrey

AU - Caron, Olivier

AU - Hardouin, Agnès

AU - Berthet, Pascaline

AU - Hogervorst, Frans B.L.

AU - Rookus, Matti A.

AU - Jager, Agnes

AU - Van Den Ouweland, Ans

AU - Hoogerbrugge, Nicoline

AU - Van Der Luijt, Rob B.

AU - Meijers-Heijboer, Hanne

AU - G'mez García, Encarna B.

AU - Devilee, Peter

AU - Vreeswijk, Maaike P.G.

AU - Lubinski, Jan

AU - Jakubowska, Anna

AU - Gronwald, Jacek

AU - Huzarski, Tomasz

AU - Byrski, Tomasz

AU - G'rski, Bohdan

AU - Cybulski, Cezary

AU - Spurdle, Amanda B.

AU - Holland, Helene

AU - Goldgar, David E.

AU - John, Esther M.

AU - Hopper, John L.

AU - Southey, Melissa

AU - Buys, Saundra S.

AU - Daly, Mary B.

AU - Terry, Mary Beth

AU - Schmutzler, Rita K.

AU - Wappenschmidt, Barbara

AU - Engel, Christoph

AU - Meindl, Alfons

AU - Preisler-Adams, Sabine

AU - Arnold, Norbert

AU - Niederacher, Dieter

AU - Sutter, Christian

AU - Domchek, Susan M.

AU - Nathanson, Katherine L.

AU - Rebbeck, Timothy

AU - Blum, Joanne L.

AU - Piedmonte, Marion

AU - Rodriguez, Gustavo C.

AU - Wakeley, Katie

AU - Boggess, John F.

AU - Basil, Jack

AU - Blank, Stephanie V.

AU - Friedman, Eitan

AU - Kaufman, Bella

AU - Laitman, Yael

AU - Milgrom, Roni

AU - Andrulis, Irene L.

AU - Glendon, Gord

AU - Ozcelik, Hilmi

AU - Kirchhoff, Tomas

AU - Vijai, Joseph

AU - Gaudet, Mia M.

AU - Altshuler, David

AU - Guiducci, Candace

AU - Loman, Niklas

AU - Harbst, Katja

AU - Rantala, Johanna

AU - Ehrencrona, Hans

AU - Gerdes, Anne Marie

AU - Thomassen, Mads

AU - Sunde, Lone

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Bonanni, Bernardo

AU - Viel, Alessandra

AU - Radice, Paolo

AU - Caldes, Trinidad

AU - De La Hoya, Miguel

AU - Singer, Christian F.

AU - Fink-Retter, Anneliese

AU - Greene, Mark H.

AU - Mai, Phuong L.

AU - Loud, Jennifer T.

AU - Guidugli, Lucia

AU - Lindor, Noralane M.

AU - Hansen, Thomas V.O.

AU - Nielsen, Finn C.

AU - Blanco, Ignacio

AU - Lazaro, Conxi

AU - Garber, Judy

AU - Ramus, Susan J.

AU - Gayther, Simon A.

AU - Phelan, Catherine

AU - Narod, Stephen

AU - Szabo, Csilla I.

AU - Benitez, Javier

AU - Osorio, Ana

AU - Nevanlinna, Heli

AU - Heikkinen, Tuomas

AU - Caligo, Maria A.

AU - Beattie, Mary S.

AU - Hamann, Ute

AU - Godwin, Andrew K.

AU - Montagna, Marco

AU - Casella, Cinzia

AU - Neuhausen, Susan L.

AU - Karlan, Beth Y.

AU - Tung, Nadine

AU - Toland, Amanda E.

AU - Weitzel, Jeffrey

AU - Olopade, Olofunmilayo

AU - Simard, Jacques

AU - Soucy, Penny

AU - Rubinstein, Wendy S.

AU - Arason, Adalgeir

AU - Rennert, Gad

AU - Martin, Nicholas G.

AU - Montgomery, Grant W.

AU - Chang-Claude, Jenny

AU - Flesch-Janys, Dieter

AU - Brauch, Hiltrud

AU - Severi, Gianluca

AU - Baglietto, Laura

AU - Cox, Angela

AU - Cross, Simon S.

AU - Miron, Penelope

AU - Gerty, Sue M.

AU - Tapper, William

AU - Yannoukakos, Drakoulis

AU - Fountzilas, George

AU - Fasching, Peter A.

AU - Beckmann, Matthias W.

AU - Dos Santos Silva, Isabel

AU - Peto, Julian

AU - Lambrechts, Diether

AU - Paridaens, Robert

AU - Rüdiger, Thomas

AU - Försti, Asta

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Diasio, Robert B.

AU - Lee, Adam M.

AU - Eckel-Passow, Jeanette

AU - Vachon, Celine

AU - Blows, Fiona

AU - Driver, Kristy

AU - Dunning, Alison

AU - Pharoah, Paul P.D.

AU - Offit, Kenneth

AU - Pankratz, V. Shane

AU - Hakonarson, Hakon

AU - Chenevix-Trench, Georgia

AU - Easton, Douglas F.

AU - Couch, Fergus J.

PY - 2010/9

Y1 - 2010/9

N2 - Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P trend = 2.3 × 10 9 to P trend = 3.9 × 10 7), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 × 10 7 to P trend = 8 × 10 5; rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P trend = 1.1 × 10 7).

AB - Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P trend = 2.3 × 10 9 to P trend = 3.9 × 10 7), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 × 10 7 to P trend = 8 × 10 5; rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P trend = 1.1 × 10 7).

KW - Adult

KW - BRCA1 Protein/genetics

KW - Breast Neoplasms/genetics

KW - Case-Control Studies

KW - Chromosomes, Human, Pair 19/genetics

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Mutation/genetics

KW - Polymorphism, Single Nucleotide/genetics

KW - Receptor, ErbB-2/genetics

KW - Receptors, Estrogen/genetics

KW - Receptors, Progesterone/genetics

UR - https://www.scopus.com/pages/publications/77957568513

UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000282276600020&DestLinkType=FullRecord&DestApp=WOS

U2 - 10.1038/ng.669

DO - 10.1038/ng.669

M3 - Article

C2 - 20852631

SN - 1061-4036

VL - 42

SP - 885

EP - 892

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

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