Article
Body mass index and breast cancer survival: a Mendelian randomization analysis
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- (1) University of Cambridge, grid.5335.0
- (2) Harvard University, grid.38142.3c
- (3) Cambridge Experimental Cancer Medicine Centre, Cambridge, UK
- (4) Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
- (5) Mount Sinai Hospital, grid.416166.2
- (6) University of Toronto, grid.17063.33
- (7) University of Melbourne, grid.1008.9
- (8) German Cancer Research Center, grid.7497.d
- (9) Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain
- (10) Spanish National Cancer Research Centre, grid.7719.8
- (11) National Cancer Institute, grid.48336.3a
- (12) Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
- (13) Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- (14) University of Copenhagen, grid.5254.6, KU
- (15) European Institute of Oncology, grid.15667.33
- (16) Karolinska Institute, grid.4714.6
- (17) Antoni van Leeuwenhoek Hospital, grid.430814.a
- (18) Heidelberg University, grid.7700.0
- (19) Cancer Research UK Cambridge Institute, grid.470869.4
- (20) University of Pisa, grid.5395.a
- (21) University Cancer Center Hamburg, grid.412315.0
- (22) Mayo Clinic, grid.66875.3a
- (23) University of Sheffield, grid.11835.3e
- (24) Pomeranian Medical University, grid.107950.a
- (25) Leiden University Medical Center, grid.10419.3d
- (26) American Cancer Society, grid.422418.9
- (27) University of Southampton, grid.5491.9
- (28) Institute of Human Genetics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- (29) University of Manchester, grid.5379.8
- (30) University of California, Los Angeles, grid.19006.3e
- (31) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- (32) University of Edinburgh, grid.4305.2
- (33) University Medical Center Hamburg-Eppendorf, grid.13648.38
- (34) Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- (35) Cancer Council Victoria, grid.3263.4
- (36) Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
- (37) University of Southern California, grid.42505.36
- (38) University of Massachusetts Amherst, grid.266683.f
- (39) University of Eastern Finland, grid.9668.1
- (40) Kuopio University Hospital, grid.410705.7
- (41) University of Warwick, grid.7372.1
- (42) Krebsregister Saarland, grid.482902.5
- (43) Erasmus University Medical Center, grid.5645.2
- (44) Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland
- (45) Central Finland Health Care District, grid.460356.2
- (46) Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
- (47) Oslo University Hospital, grid.55325.34
- (48) University of Oslo, grid.5510.1
- (49) Flanders Institute for Biotechnology, grid.11486.3a
- (50) KU Leuven, grid.5596.f
- (51) University of Hawaii at Manoa, grid.410445.0
- (52) University of Washington, grid.34477.33
- (53) Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center – Oncology Institute, Warsaw, Poland
- (54) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
- (55) National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
- (56) The Alfred Hospital, grid.1623.6
- (57) Hospital Monte Naranco, grid.414858.4
- (58) University Health Network, grid.231844.8
- (59) Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
- (60) Universitair Ziekenhuis Leuven, grid.410569.f
- (61) Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- (62) IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy
- (63) Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Australia
- (64) Peter MacCallum Cancer Centre, grid.1055.1
- (65) Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland
- (66) University of Oulu, grid.10858.34
- (67) Institute of Cancer Research, grid.18886.3f
- (68) Städtisches Klinikum Karlsruhe, grid.419594.4
- (69) King's College London, grid.13097.3c
- (70) Case Western Reserve University, grid.67105.35
- (71) University of Oxford, grid.4991.5
- (72) Klinikum Mittelbaden, grid.506801.a
- (73) Hospital Universitario La Paz, grid.81821.32
- (74) QIMR Berghofer Medical Research Institute, grid.1049.c
- (75) Hannover Medical School, grid.10423.34
- (76) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA and
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Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer. Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95). Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.
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