Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

kConFab/AOCS Investigators

doi:10.1038/s41598-021-99409-3

Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

kConFab/AOCS Investigators

Peter Maccallum Cancer Centre
Antoni van Leeuwenhoek Hospital
Queensland Institute of Medical Research
University of California at Irvine
German Cancer Research Center
Lund University
University of Hamburg
Friedrich-Alexander University Erlangen-Nürnberg
Russian Academy of Sciences
University of Copenhagen
University of Cambridge
Oncology and Genetics Unit
National Institutes of Health
Mayo Clinic
Karolinska Institutet
Leiden University
Hannover Medical School
Brigham and Women's Hospital
Harvard University
University of California at Los Angeles
Complejo Hospitalario Universitario de Santiago
University of California at San Diego
Hospital Clínico San Carlos de Madrid
University of Oslo
Cancer Council Victoria
Centre for Epidemiology and Biostatistics
Monash University
University of Oulu
Heidelberg University
Helmholtz Zentrum München - German Research Center for Environmental Health
University of Cologne
University of Southern California
Sšdersjukhuset
University of Eastern Finland
Erasmus University Rotterdam
Robert Bosch Foundation
University of Tübingen
University of Oxford
Université de Montpellier
Pomeranian Medical University in Szczecin
Stanford University
Ufa University of Science and Technology
Flanders Institute for Biotechnology
KU Leuven
University of Hawai'i at Mānoa
Moorfields Eye Hospital NHS Foundation Trust
Heraklion University Hospital
Helsinki University Hospital
University of North Carolina at Chapel Hill
American Cancer Society
FIRC Institute of Molecular Oncology
Fondazione IRCCS Istituto Nazionale dei Tumori
Technion-Israel Institute of Technology
Universidad Autónoma de Madrid
University College London Hospitals NHS Foundation Trust
Städtischen Klinikum Karlsruhe
University Hospital of Larissa
King's College London
Royal Marsden Hospital
Department of Clinical Pathology
Cornell University
Universite Claude Bernard Lyon 1
University of Birmingham
Northern Finland Laboratory Centre Oulu
Uppsala University
Cyprus Institute of Neurology and Genetics
Centre Léon Bérard

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

4 Scopus citations

Abstract

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10⁻⁸ and 4.42 × 10⁻⁸). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

Original language	English
Article number	19787
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-99409-3
State	Published - Dec 2021

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@article{d9caea03cb2f47efabf76600f091a058,

title = "Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis",

abstract = "Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.",

author = "\{kConFab/AOCS Investigators\} and Maria Escala-Garcia and Sander Canisius and Renske Keeman and Jonathan Beesley and Hoda Anton-Culver and Volker Arndt and Annelie Augustinsson and Heiko Becher and Beckmann, \{Matthias W.\} and Sabine Behrens and Marina Bermisheva and Bojesen, \{Stig E.\} and Bolla, \{Manjeet K.\} and Hermann Brenner and Federico Canzian and Castelao, \{Jose E.\} and Jenny Chang-Claude and Chanock, \{Stephen J.\} and Couch, \{Fergus J.\} and Kamila Czene and Daly, \{Mary B.\} and Joe Dennis and Peter Devilee and Thilo D{\"o}rk and Dunning, \{Alison M.\} and Easton, \{Douglas F.\} and Ekici, \{Arif B.\} and Eliassen, \{A. Heather\} and Fasching, \{Peter A.\} and Henrik Flyger and Manuela Gago-Dominguez and Montserrat Garc{\'i}a-Closas and Garc{\'i}a-S{\'a}enz, \{Jos{\'e} A.\} and J{\"u}rgen Geisler and Giles, \{Graham G.\} and Mervi Grip and Melanie G{\"u}ndert and Eric Hahnen and Haiman, \{Christopher A.\} and Niclas H{\aa}kansson and Per Hall and Ute Hamann and Hartikainen, \{Jaana M.\} and Heemskerk-Gerritsen, \{Bernadette A.M.\} and Antoinette Hollestelle and Reiner Hoppe and Hopper, \{John L.\} and Hunter, \{David J.\} and William Jacot and Anna Jakubowska",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

doi = "10.1038/s41598-021-99409-3",

language = "English",

volume = "11",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Research",

number = "1",

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TY - JOUR

T1 - Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

AU - kConFab/AOCS Investigators

AU - Escala-Garcia, Maria

AU - Canisius, Sander

AU - Keeman, Renske

AU - Beesley, Jonathan

AU - Anton-Culver, Hoda

AU - Arndt, Volker

AU - Augustinsson, Annelie

AU - Becher, Heiko

AU - Beckmann, Matthias W.

AU - Behrens, Sabine

AU - Bermisheva, Marina

AU - Bojesen, Stig E.

AU - Bolla, Manjeet K.

AU - Brenner, Hermann

AU - Canzian, Federico

AU - Castelao, Jose E.

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J.

AU - Couch, Fergus J.

AU - Czene, Kamila

AU - Daly, Mary B.

AU - Dennis, Joe

AU - Devilee, Peter

AU - Dörk, Thilo

AU - Dunning, Alison M.

AU - Easton, Douglas F.

AU - Ekici, Arif B.

AU - Eliassen, A. Heather

AU - Fasching, Peter A.

AU - Flyger, Henrik

AU - Gago-Dominguez, Manuela

AU - García-Closas, Montserrat

AU - García-Sáenz, José A.

AU - Geisler, Jürgen

AU - Giles, Graham G.

AU - Grip, Mervi

AU - Gündert, Melanie

AU - Hahnen, Eric

AU - Haiman, Christopher A.

AU - Håkansson, Niclas

AU - Hall, Per

AU - Hamann, Ute

AU - Hartikainen, Jaana M.

AU - Heemskerk-Gerritsen, Bernadette A.M.

AU - Hollestelle, Antoinette

AU - Hoppe, Reiner

AU - Hopper, John L.

AU - Hunter, David J.

AU - Jacot, William

AU - Jakubowska, Anna

PY - 2021/12

Y1 - 2021/12

N2 - Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

AB - Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

UR - https://www.scopus.com/pages/publications/85116813839

U2 - 10.1038/s41598-021-99409-3

DO - 10.1038/s41598-021-99409-3

M3 - Article

C2 - 34611289

SN - 2045-2322

VL - 11

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 19787

ER -

Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

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