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 associa...
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Nature Portfolio
2021
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oai:doaj.org-article:15d48d4f4e3145c29057f7c26462140f2021-12-02T18:37:09ZGermline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis10.1038/s41598-021-99409-32045-2322https://doaj.org/article/15d48d4f4e3145c29057f7c26462140f2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99409-3https://doaj.org/toc/2045-2322Abstract 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.Maria Escala-GarciaSander CanisiusRenske KeemanJonathan BeesleyHoda Anton-CulverVolker ArndtAnnelie AugustinssonHeiko BecherMatthias W. BeckmannSabine BehrensMarina BermishevaStig E. BojesenManjeet K. BollaHermann BrennerFederico CanzianJose E. CastelaoJenny Chang-ClaudeStephen J. ChanockFergus J. CouchKamila CzeneMary B. DalyJoe DennisPeter DevileeThilo DörkAlison M. DunningDouglas F. EastonArif B. EkiciA. Heather EliassenPeter A. FaschingHenrik FlygerManuela Gago-DominguezMontserrat García-ClosasJosé A. García-SáenzJürgen GeislerGraham G. GilesMervi GripMelanie GündertEric HahnenChristopher A. HaimanNiclas HåkanssonPer HallUte HamannJaana M. HartikainenBernadette A. M. Heemskerk-GerritsenAntoinette HollestelleReiner HoppeJohn L. HopperDavid J. HunterWilliam JacotAnna JakubowskaEsther M. JohnAudrey Y. JungRudolf KaaksElza KhusnutdinovaLinetta B. KoppertPeter KraftVessela N. KristensenAllison W. KurianDiether LambrechtsLoic Le MarchandAnnika LindblomRobert N. LubenJan LubińskiArto MannermaaMehdi ManoochehriSara MargolinDimitrios MavroudisTaru A. MuranenHeli NevanlinnaAndrew F. OlshanHåkan OlssonTjoung-Won Park-SimonAlpa V. PatelPaolo PeterlongoPaul D. P. PharoahKevin PuniePaolo RadiceGad RennertHedy S. RennertAtocha RomeroRebecca RoylanceThomas RüdigerMatthias RuebnerEmmanouil SaloustrosElinor J. SawyerRita K. SchmutzlerMinouk J. SchoemakerChristopher ScottMelissa C. SoutheyHarald SurowyAnthony J. SwerdlowRulla M. TamimiLauren R. TerasEmilie ThomasIan TomlinsonMelissa A. TroesterCeline M. VachonQin WangRobert WinqvistAlicja WolkArgyrios ZiogaskConFab/AOCS InvestigatorsKyriaki MichailidouGeorgia Chenevix-TrenchThomas BachelotMarjanka K. SchmidtNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
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DOAJ |
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Medicine R Science Q 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. Couch Kamila 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 Esther M. John Audrey Y. Jung Rudolf Kaaks Elza Khusnutdinova Linetta B. Koppert Peter Kraft Vessela N. Kristensen Allison W. Kurian Diether Lambrechts Loic Le Marchand Annika Lindblom Robert N. Luben Jan Lubiński Arto Mannermaa Mehdi Manoochehri Sara Margolin Dimitrios Mavroudis Taru A. Muranen Heli Nevanlinna Andrew F. Olshan Håkan Olsson Tjoung-Won Park-Simon Alpa V. Patel Paolo Peterlongo Paul D. P. Pharoah Kevin Punie Paolo Radice Gad Rennert Hedy S. Rennert Atocha Romero Rebecca Roylance Thomas Rüdiger Matthias Ruebner Emmanouil Saloustros Elinor J. Sawyer Rita K. Schmutzler Minouk J. Schoemaker Christopher Scott Melissa C. Southey Harald Surowy Anthony J. Swerdlow Rulla M. Tamimi Lauren R. Teras Emilie Thomas Ian Tomlinson Melissa A. Troester Celine M. Vachon Qin Wang Robert Winqvist Alicja Wolk Argyrios Ziogas kConFab/AOCS Investigators Kyriaki Michailidou Georgia Chenevix-Trench Thomas Bachelot Marjanka K. Schmidt Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis |
| description |
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. |
| format |
article |
| author |
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. Couch Kamila 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 Esther M. John Audrey Y. Jung Rudolf Kaaks Elza Khusnutdinova Linetta B. Koppert Peter Kraft Vessela N. Kristensen Allison W. Kurian Diether Lambrechts Loic Le Marchand Annika Lindblom Robert N. Luben Jan Lubiński Arto Mannermaa Mehdi Manoochehri Sara Margolin Dimitrios Mavroudis Taru A. Muranen Heli Nevanlinna Andrew F. Olshan Håkan Olsson Tjoung-Won Park-Simon Alpa V. Patel Paolo Peterlongo Paul D. P. Pharoah Kevin Punie Paolo Radice Gad Rennert Hedy S. Rennert Atocha Romero Rebecca Roylance Thomas Rüdiger Matthias Ruebner Emmanouil Saloustros Elinor J. Sawyer Rita K. Schmutzler Minouk J. Schoemaker Christopher Scott Melissa C. Southey Harald Surowy Anthony J. Swerdlow Rulla M. Tamimi Lauren R. Teras Emilie Thomas Ian Tomlinson Melissa A. Troester Celine M. Vachon Qin Wang Robert Winqvist Alicja Wolk Argyrios Ziogas kConFab/AOCS Investigators Kyriaki Michailidou Georgia Chenevix-Trench Thomas Bachelot Marjanka K. Schmidt |
| author_facet |
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. Couch Kamila 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 Esther M. John Audrey Y. Jung Rudolf Kaaks Elza Khusnutdinova Linetta B. Koppert Peter Kraft Vessela N. Kristensen Allison W. Kurian Diether Lambrechts Loic Le Marchand Annika Lindblom Robert N. Luben Jan Lubiński Arto Mannermaa Mehdi Manoochehri Sara Margolin Dimitrios Mavroudis Taru A. Muranen Heli Nevanlinna Andrew F. Olshan Håkan Olsson Tjoung-Won Park-Simon Alpa V. Patel Paolo Peterlongo Paul D. P. Pharoah Kevin Punie Paolo Radice Gad Rennert Hedy S. Rennert Atocha Romero Rebecca Roylance Thomas Rüdiger Matthias Ruebner Emmanouil Saloustros Elinor J. Sawyer Rita K. Schmutzler Minouk J. Schoemaker Christopher Scott Melissa C. Southey Harald Surowy Anthony J. Swerdlow Rulla M. Tamimi Lauren R. Teras Emilie Thomas Ian Tomlinson Melissa A. Troester Celine M. Vachon Qin Wang Robert Winqvist Alicja Wolk Argyrios Ziogas kConFab/AOCS Investigators Kyriaki Michailidou Georgia Chenevix-Trench Thomas Bachelot Marjanka K. Schmidt |
| author_sort |
Maria Escala-Garcia |
| title |
Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis |
| title_short |
Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis |
| title_full |
Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis |
| title_fullStr |
Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis |
| title_full_unstemmed |
Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis |
| title_sort |
germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/15d48d4f4e3145c29057f7c26462140f |
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