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Get Free AccessBreast 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.
Jose E. Castelao, Julia Geisler, R.M. Tamimi, Maria Escala-Garcia, Sara Margolin, Minouk J. Schoemaker, Anna Jakubowska, Anthony J. Swerdlow, Alison M. Dunning, David J. Hunter, Melanie Gündert, Harald Surowy, Jaana M. Hartikainen, Peter Kraft, Niclas Håkansson, Thomas Rüdiger, Q. Wang, M.A. Troester, Diether Lambrechts, M. Daly, William Jacot, Kamila Czene, M.W. Beckmann, Heli Nevanlinna, Heiko Becher, Thilo Dörk, Annelie Augustinsson, Kyriaki Michailidou, Tjoung‐Won Park‐Simon, kConFab AOCS Investigators, Manjeet K. Bolla, Atocha Romero, Arif B. Ekici, Ian Tomlinson, D. Mavroudis, P.D.P. Pharoah, M Schmidt, Celine M. Vachon, Georgia Chenevix‐Trench, F.J. Couch, Joe Dennis, A.F. Olshan, J. Chang-Claude, R. Kaaks, Renske Keeman, Hedy S. Rennert, Sander Canisius, Antoinette Hollestelle, U. Hamann, Eric Hahnen, Vessela N. Kristensen, Robert Winqvist, L. Le Marchand, Christopher J. Scott, Hermann Brenner, Lauren R. Teras, T. Bachelot, Per Hall, A. Wolk, Emilie Thomas, Sabine Behrens, Matthias Ruebner, Jan Lubiński, Linetta B. Koppert, T.A. Muranen, R.K. Schmutzler, K. Punie, Melissa C. Southey, Esther M. John, A. Heather Eliassen, Håkan Olsson, Э. К. Хуснутдинова, J. Beesley, Robert Luben, P. Peterlongo, Reiner Hoppe, Volker Arndt, P. Devilee, Elinor J. Sawyer, Masood Manoochehri, A. Lindblom, José Á. García-Sáenz, Argyrios Ziogas, S.J. Chanock, Paolo Radice, Stig E. Bojesen, Arto Mannermaa, D.F. Easton, H. Anton-Culver, Audrey Jung, Mervi Grip, P.A. Fasching, Federico Canzian, Montserrat García‐Closas, G. Rennert, Christopher A. Haiman, Rebecca Roylance, B.A.M. Heemskerk-Gerritsen, A.V. Patel, Graham G. Giles (2024). Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis. , DOI: https://doi.org/10.17615/facv-0d26.
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Type
Article
Year
2024
Authors
100
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.17615/facv-0d26
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