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

Taru A. Muranen, Sofia Khan, Rainer Fagerholm, Kristiina Aittomäki, Julie M. Cunningham, Joe Dennis, Goska Leslie, Lesley McGuffog, Michael T. Parsons, Jacques Simard, Susan Slager, Penny Soucy, Douglas F. Easton, Marc Tischkowitz, Amanda B. Spurdle, kConFab Investigators, Rita K. Schmutzler, Barbara Wappenschmidt, Eric Hahnen, Maartje J. HooningHEBON Investigators, Christian F. Singer, Gabriel Wagner, Mads Thomassen, Inge Sokilde Pedersen, Susan M. Domchek, Katherine L. Nathanson, Conxi Lazaro, Caroline Maria Rossing, Irene L. Andrulis, Manuel R. Teixeira, Paul James, Judy Garber, Jeffrey N. Weitzel, SWE-BRCA Investigators, Anna Jakubowska, Drakoulis Yannoukakos, Esther M. John, Melissa C. Southey, Marjanka K. Schmidt, Antonis C. Antoniou, Georgia Chenevix-Trench, Carl Blomqvist, Heli Nevanlinna

Research output: Contribution to journalArticleResearchpeer-review


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.

Original languageEnglish
Article number44
Number of pages13
Journalnpj Breast Cancer
Issue number1
Publication statusPublished - 1 Dec 2020

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