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2024
article
Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment
Stella Koutros, Wolfgang Janni, B Rack, D.F. Easton, Per Hall, Clare L. Scott, Volker Arndt, Sebastian Nielsen, Arif B. Ekici, Mikael Eriksson, José Á. García-Sáenz, Nick Orr, Sara Margolin, Ting Cheng, Agnes Jager, Christine L. Clarke, Bette J. Caan, Argyrios Ziogas, Mitul Shah, Harald Surowy, A.F. Olshan, Valerie Rhenius, T. Brüning, R. Kaaks, Kyriaki Michailidou, Georgia Chenevix‐Trench, Kamila Czene, Paul L. Auer, Rebecca Roylance, Ian Tomlinson, Hiltrud Brauch, Angela Cox, Henrik Flyger, Nadège Presneau, ABCTB Investigators, Peter Kraft, A. Wolk, Esther M. John, Wei He, D. Gareth Evans, Matthias Ruebner, Joe Dennis, Pascal Guénel, Annelie Augustinsson, Thomas U. Ahearn, Dijana Plaseska-Karanfilska, Graham G. Giles, Reiner Hoppe, kConFab Investigators, Q. Wang, RM Tamimi, Tjoung‐Won Park‐Simon, Bernard Peissel, Audrey Jung, NBCS Collaborators, Sabine Behrens, Marı́a Elena Martı́nez, Jose E. Castelao, Heli Nevanlinna, A. Lindblom, A Swerdlow, Snezhana Smichkoska, William Tapper, Anthony Howell, Machteld Keupers, SS Buys, Martha S. Linet, Simon S. Cross, A.V. Patel, A. Heather Eliassen, Manuela Gago-Domínguez, A. Schneeweiss, R.A.E.M. Tollenaar, Jan Lubiński, Steven N. Hart, Masood Manoochehri, Diether Lambrechts, K. Prajzendanc, Michael Lush, Anna Marie Mulligan, Emmanouil Saloustros, Thilo Dörk, Heiko Becher, M.W. Beckmann, Niclas Håkansson, David J. Hunter, Alain Hartmann, P. Peterlongo, Atocha Romero, Allison W. Kurian, M. Bolla, Laure Dossus, Peter A. Fasching, Melissa C. Southey, Robert Winqvist, Thérèse Truong, J. Lacey, Montserrat García‐Closas, William G. Newman, L. Le Marchand, Hermann Brenner, Celine M. Vachon, Melanie Gündert, U. Hamann, Diana Eccles, Håkan Olsson, Arto Mannermaa, Emma Sawyer, Jennifer Stone, Børge G. Nordestgaard, Stig E. Bojesen, Ross L. Prentice, G. Rennert, Daniele Campa, Sander Canisius, Maria Escala-Garcia, A.M. Dunning, Lin Fritschi, Lauren R. Teras, C.A. Haiman, Hedy S. Rennert, Anna Jakubowska, R Schmutzler, Renske Keeman, Mary Beth Terry, Robert Luben, M Schmidt, Anna Morra, M.B. Daly, Laura E. Beane Freeman, Roger L. Milne, M.A. Troester, Sarah V. Colonna, Jenny Chang‐Claude, J.W.M. Martens, Cari M. Kitahara, Jaana M. Hartikainen, Maartje J. Hooning, T.A. Muranen, Amber N. Hurson, Vessela N. Kristensen, Paul D.P. Pharoah, J. Beesley, Federico Canzian, I.L. Andrulis, Miriam Dwek, H. Anton-Culver, Mervi Grip, D. Mavroudis, F.J. Couch, JL Hopper, S.J. Chanock
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Rattachement africain : us.
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Background: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). Results: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E−08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E−07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E−08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E−08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.
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Les sujets associés
BRCA gene mutations in cancerMultiple and Secondary Primary Cancers