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Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

Authors :
Douglas F. Easton
Mads Thomassen
Georgia Chenevix-Trench
Kristiina Aittomäki
Marjanka K. Schmidt
Hebon Investigators
Esther M. John
Irene L. Andrulis
Maartje J. Hooning
Antonis C. Antoniou
Swe-Brca Investigators
Caroline Maria Rossing
Penny Soucy
Jacques Simard
Michael T. Parsons
Julie M. Cunningham
Paul A. James
Joe Dennis
Gabriel Wagner
Melissa C. Southey
Susan M. Domchek
Eric Hahnen
kConFab Investigators
Goska Leslie
Sofia Khan
Katherine L. Nathanson
Rita K. Schmutzler
Anna Jakubowska
Jeffrey N. Weitzel
Taru A. Muranen
Heli Nevanlinna
Barbara Wappenschmidt
Drakoulis Yannoukakos
Judy Garber
Marc Tischkowitz
Conxi Lázaro
Inge Søkilde Pedersen
Carl Blomqvist
Amanda B. Spurdle
Christian F. Singer
Susan L. Slager
Lesley McGuffog
Rainer Fagerholm
Manuel R. Teixeira
Medical Oncology
HUS Gynecology and Obstetrics
Department of Obstetrics and Gynecology
University of Helsinki
Helsinki University Hospital Area
Medicum
Kristiina Aittomäki / Principal Investigator
HUSLAB
Department of Medical and Clinical Genetics
HUS Comprehensive Cancer Center
Department of Oncology
Clinicum
Muranen, Taru A. [0000-0002-5895-1808]
Cunningham, Julie M. [0000-0002-8159-3025]
Dennis, Joe [0000-0003-4591-1214]
Leslie, Goska [0000-0001-5756-6222]
Parsons, Michael T. [0000-0003-3242-8477]
Simard, Jacques [0000-0001-6906-3390]
Easton, Douglas F. [0000-0003-2444-3247]
Spurdle, Amanda B. [0000-0003-1337-7897]
Pedersen, Inge Sokilde [0000-0002-9902-8040]
Nathanson, Katherine L. [0000-0002-6740-0901]
Lazaro, Conxi [0000-0002-7198-5906]
Andrulis, Irene L. [0000-0002-4226-6435]
Teixeira, Manuel R. [0000-0002-4896-5982]
James, Paul [0000-0002-4361-4657]
Weitzel, Jeffrey N. [0000-0001-6714-092X]
Jakubowska, Anna [0000-0002-5650-0501]
Yannoukakos, Drakoulis [0000-0001-7509-3510]
Schmidt, Marjanka K. [0000-0002-2228-429X]
Nevanlinna, Heli [0000-0002-0916-2976]
Apollo - University of Cambridge Repository
Muranen, Taru A [0000-0002-5895-1808]
Cunningham, Julie M [0000-0002-8159-3025]
Parsons, Michael T [0000-0003-3242-8477]
Easton, Douglas F [0000-0003-2444-3247]
Spurdle, Amanda B [0000-0003-1337-7897]
Nathanson, Katherine L [0000-0002-6740-0901]
Andrulis, Irene L [0000-0002-4226-6435]
Teixeira, Manuel R [0000-0002-4896-5982]
Weitzel, Jeffrey N [0000-0001-6714-092X]
Schmidt, Marjanka K [0000-0002-2228-429X]
Source :
Muranen, T A, Khan, S, Fagerholm, R, Aittomäki, K, Cunningham, J M, Dennis, J, Leslie, G, McGuffog, L, Parsons, M T, Simard, J, Slager, S, Soucy, P, Easton, D F, Tischkowitz, M, Spurdle, A B, kConFab Investigators, Schmutzler, R K, Wappenschmidt, B, Hahnen, E, Hooning, M J, HEBON Investigators, Singer, C F, Wagner, G, Thomassen, M, Pedersen, I S, Domchek, S M, Nathanson, K L, Lazaro, C, Rossing, C M, Andrulis, I L, Teixeira, M R, James, P, Garber, J, Weitzel, J N, SWE-BRCA Investigators, Jakubowska, A, Yannoukakos, D, John, E M, Southey, M C, Schmidt, M K, Antoniou, A C, Chenevix-Trench, G, Blomqvist, C & Nevanlinna, H 2020, ' Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer ', npj Breast Cancer, vol. 6, no. 1, 44 . https://doi.org/10.1038/s41523-020-00185-6, Muranen, T A, Khan, S, Fagerholm, R, Aittomäki, K, Cunningham, J M, Dennis, J, Leslie, G, McGuffog, L, Parsons, M T, Simard, J, Slager, S, Soucy, P, Easton, D F, Tischkowitz, M, Spurdle, A B, Schmutzler, R K, Wappenschmidt, B, Hahnen, E, Hooning, M J, Singer, C F, Wagner, G, Thomassen, M, Pedersen, I S, Domchek, S M, Nathanson, K L, Lazaro, C, Rossing, C M, Andrulis, I L, Teixeira, M R, James, P, Garber, J, Weitzel, J N, Jakubowska, A, Yannoukakos, D, John, E M, Southey, M C, Schmidt, M K, Antoniou, A C, Chenevix-Trench, G, Blomqvist, C, Nevanlinna, H, kConFab Investigators, HEBON Investigators & SWE-BRCA Investigators 2020, ' Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer ', npj Breast Cancer, vol. 6, 44 . https://doi.org/10.1038/s41523-020-00185-6, npj Breast Cancer, 6(1):44. Nature Publishing Group, Dipòsit Digital de la UB, Universidad de Barcelona, npj Breast Cancer, Vol 6, Iss 1, Pp 1-13 (2020), NPJ Breast Cancer
Publication Year :
2020

Abstract

Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03–6.30, P = 3.1 × 10−9). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics.

Details

Language :
English
ISSN :
23744677
Database :
OpenAIRE
Journal :
Muranen, T A, Khan, S, Fagerholm, R, Aittomäki, K, Cunningham, J M, Dennis, J, Leslie, G, McGuffog, L, Parsons, M T, Simard, J, Slager, S, Soucy, P, Easton, D F, Tischkowitz, M, Spurdle, A B, kConFab Investigators, Schmutzler, R K, Wappenschmidt, B, Hahnen, E, Hooning, M J, HEBON Investigators, Singer, C F, Wagner, G, Thomassen, M, Pedersen, I S, Domchek, S M, Nathanson, K L, Lazaro, C, Rossing, C M, Andrulis, I L, Teixeira, M R, James, P, Garber, J, Weitzel, J N, SWE-BRCA Investigators, Jakubowska, A, Yannoukakos, D, John, E M, Southey, M C, Schmidt, M K, Antoniou, A C, Chenevix-Trench, G, Blomqvist, C & Nevanlinna, H 2020, ' Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer ', npj Breast Cancer, vol. 6, no. 1, 44 . https://doi.org/10.1038/s41523-020-00185-6, Muranen, T A, Khan, S, Fagerholm, R, Aittomäki, K, Cunningham, J M, Dennis, J, Leslie, G, McGuffog, L, Parsons, M T, Simard, J, Slager, S, Soucy, P, Easton, D F, Tischkowitz, M, Spurdle, A B, Schmutzler, R K, Wappenschmidt, B, Hahnen, E, Hooning, M J, Singer, C F, Wagner, G, Thomassen, M, Pedersen, I S, Domchek, S M, Nathanson, K L, Lazaro, C, Rossing, C M, Andrulis, I L, Teixeira, M R, James, P, Garber, J, Weitzel, J N, Jakubowska, A, Yannoukakos, D, John, E M, Southey, M C, Schmidt, M K, Antoniou, A C, Chenevix-Trench, G, Blomqvist, C, Nevanlinna, H, kConFab Investigators, HEBON Investigators & SWE-BRCA Investigators 2020, ' Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer ', npj Breast Cancer, vol. 6, 44 . https://doi.org/10.1038/s41523-020-00185-6, npj Breast Cancer, 6(1):44. Nature Publishing Group, Dipòsit Digital de la UB, Universidad de Barcelona, npj Breast Cancer, Vol 6, Iss 1, Pp 1-13 (2020), NPJ Breast Cancer
Accession number :
edsair.doi.dedup.....a4a9b318f5e628e5474d4bbd4fbfbf67