Journal article

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 Aittomaeki, 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, Rita K Schmutzler, Barbara Wappenschmidt, Eric Hahnen, Maartje J Hooning, Christian F Singer Show all

NPJ BREAST CANCER | NATURE PORTFOLIO | Published : 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..

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Grants

Awarded by Cancer Research-UK


Awarded by government of Canada through Genome Canada


Awarded by US National Institutes of Health (NIH)


Awarded by Cancer Research UK


Awarded by National R&D Program for Cancer Control-Ministry of Health and Welfare (Republic of Korea)


Awarded by Italian Association for Cancer Research (AIRC)


Awarded by German Cancer Aid


Awarded by government of Canada through the Canadian Institutes of Health Research


Funding Acknowledgements

We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians, and administrative staff who have enabled this work to be carried out. The CIMBA data management and data analysis were supported by Cancer Research-UK grants C12292/A20861 and C12292/A11174. Genotyping for the OncoArray was funded by the government of Canada through Genome Canada and the Canadian Institutes of Health Research (GPH-129344), the Ministere de l'Economie, de la Science et de l'Innovation du Quebec through Genome Quebec, the Quebec Breast Cancer Foundation for the PERSPECTIVE project, the US National Institutes of Health (NIH; 1 U19 CA 148065 for the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project and X01HG007492 to the Center for Inherited Disease Research (CIDR) under contract HHSN268201200008I), Cancer Research UK (C1287/A16563), the Odense University Hospital Research Foundation (Denmark), the National R&D Program for Cancer Control-Ministry of Health and Welfare (Republic of Korea; 1420190), the Italian Association for Cancer Research (AIRC; IG16933), the Breast Cancer Research Foundation, the National Health and Medical Research Council (Australia) and German Cancer Aid (110837). Detailed acknowledgements appear in the Supplementary note.