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

Escala-Garcia M, Canisius S, Keeman R, Beesley J, Anton-Culver H, Arndt V, Augustinsson A, Becher H, Beckmann M, Behrens S, Bermisheva M, Bojesen SE, Bolla MK, Brenner H, Canzian F, Castelao JE, Chang-Claude J, Chanock SJ, Couch FJ, Czene K, Daly MB, Dennis J, Devilee P, Dork T, Dunning AM, Easton DF, Ekici AB, Eliassen AH, Fasching P, Flyger H, Gago-Dominguez M, Garcia-Closas M, Garcia-Saenz JA, Geisler J, Giles GG, Grip M, Guendert M, Hahnen E, Haiman CA, Hakansson N, Hall P, Hamann U, Hartikainen JM, Heemskerk-Gerritsen BAM, Hollestelle A, Hoppe R, Hopper JL, Hunter DJ, Jacot W, Jakubowska A, John EM, Jung AY, Kaaks R, Khusnutdinova E, Koppert LB, Kraft P, Kristensen VN, Kurian AW, Lambrechts D, Le Marchand L, Lindblom A, Luben RN, Lubinski J, Mannermaa A, Manoochehri M, Margolin S, Mavroudis D, Muranen TA, Nevanlinna H, Olshan AF, Olsson H, Park-Simon TW, Patel AV, Peterlongo P, Pharoah PDP, Punie K, Radice P, Rennert G, Rennert HS, Romero A, Roylance R, Ruediger T, Rübner M, Saloustros E, Sawyer EJ, Schmutzler RK, Schoemaker MJ, Scott C, Southey MC, Surowy H, Swerdlow AJ, Tamimi RM, Teras LR, Thomas E, Tomlinson I, Troester MA, Vachon CM, Wang Q, Winqvist R, Wolk A, Ziogas A, Michailidou K, Chenevix-Trench G, Bachelot T, Schmidt MK (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 11

Journal Issue: 1

DOI: 10.1038/s41598-021-99409-3

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 x 10(-8) and 4.42 x 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.

Authors with CRIS profile

Involved external institutions

Karolinska Institute Sweden (SE) Fox Chase Cancer Center United States (USA) (US) University of Cambridge United Kingdom (GB) Leiden University Medical Center Netherlands (NL) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Copenhagen University Hospital Denmark (DK) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University of Eastern Finland Finland (FI) Erasmus University Medical Center (MC) Netherlands (NL) Robert-Bosch-Krankenhaus Germany (DE) The University of Melbourne Australia (AU) Harvard University United States (USA) (US) University of Montpellier / Université Montpellier France (FR) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Stanford University United States (USA) (US) Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS) Russian Federation (RU) Bashkir State University / Башкирский государственный университет Russian Federation (RU) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University of Hawaii (U.H.) United States (USA) (US) General University Hospital of Larissa Greece (GR) King’s College London United Kingdom (GB) Universität zu Köln Germany (DE) The Institute of Cancer Research (ICR) United Kingdom (GB) Mayo Clinic United States (USA) (US) Cancer Council Victoria Australia (AU) Antoni van Leeuwenhoek Netherlands (NL) University of California Irvine United States (USA) (US) Lund University / Lunds universitet Sweden (SE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Servizo Galego de Saúde Spain (ES) National Cancer Institute (NCI) United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) Complejo Hospitalario Universitario de Santiago de Compostela Spain (ES) Hospital Clínico San Carlos Spain (ES) Akershus University Hospital / Akershus universitetssykehus (Ahus) Norway (NO) Oulun Yliopisto / University of Oulo Finland (FI) University of Southern California (USC) United States (USA) (US) Moorfields Eye Hospital NHS Foundation Trust United Kingdom (GB) Södersjukhuset Sweden (SE) University General Hospital of Heraklion Greece (GR) Helsingin yliopisto / University of Helsinki Finland (FI) University of North Carolina at Chapel Hill United States (USA) (US) American Cancer Society United States (USA) (US) IFOM - FIRC Institute of Molecular Oncology Italy (IT) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Carmel Medical Center Israel (IL) Hospital Universitario Puerta de Hierro - Majadahonda Spain (ES) University College London Hospitals (UCLH) United Kingdom (GB) Städtisches Klinikum Karlsruhe Germany (DE) Université Claude Bernard Lyon 1 (UCB) France (FR) University of Birmingham United Kingdom (GB) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Centre Léon-Bérard (UNICANCER) France (FR)

How to cite

APA:

Escala-Garcia, M., Canisius, S., Keeman, R., Beesley, J., Anton-Culver, H., Arndt, V.,... Schmidt, M.K. (2021). Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-99409-3

MLA:

Escala-Garcia, Maria, et al. "Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis." Scientific Reports 11.1 (2021).

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