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

KConFab Investigators, Maria Escala-Garcia, Sander Canisius, Renske Keeman, Jonathan Beesley, Hoda Anton-Culver, Volker Arndt, Annelie Augustinsson, Heiko Becher, Matthias W Beckmann, Sabine Behrens, Marina Bermisheva, Stig E Bojesen, Manjeet K Bolla, Hermann Brenner, Federico Canzian, Jose E Castelao, Jenny Chang-Claude, Stephen J Chanock, Fergus J CouchKamila Czene, Mary B Daly, Joe Dennis, Peter Devilee, Thilo Dörk, Alison M Dunning, Douglas F Easton, Arif B Ekici, A Heather Eliassen, Peter A Fasching, Henrik Flyger, Manuela Gago-Dominguez, Montserrat García-Closas, José A García-Sáenz, Jürgen Geisler, Graham G Giles, Mervi Grip, Melanie Gündert, Eric Hahnen, Christopher A Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Jaana M Hartikainen, Bernadette A M Heemskerk-Gerritsen, Antoinette Hollestelle, Reiner Hoppe, John L Hopper, David J Hunter, William Jacot, Anna Jakubowska

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 languageEnglish
Article number19787
Pages (from-to)19787
JournalScientific Reports
Issue number1
StatePublished - Sep 5 2021


  • Biomarkers, Tumor
  • Breast Neoplasms/epidemiology
  • Cancer Survivors
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Germ Cells/metabolism
  • Germ-Line Mutation
  • Humans
  • Kaplan-Meier Estimate
  • Polymorphism, Single Nucleotide


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