Article open access publication

Body mass index and breast cancer survival: a Mendelian randomization analysis

International Journal of Epidemiology, Oxford University Press (OUP), ISSN 0300-5771

Volume 46, 6, 2017

DOI:10.1093/ije/dyx131, Dimensions: pub.1090547727, PMC: PMC5837506, PMID: 29232439,

Authors

Guo, Qi (1)
Wang, Qin (1)
Abraham, Jean (1) (3)
Benitez, Javier (9) (10)
Bojesen, Stig E (13) (14)
Caldas, Carlos (1) (3) (19)
Earl, Helena M (1) (3)
Fasching, Peter A (30) (31)
Figueroa, Jonine (11) (32)
Giles, Graham G (7) (35)
Hall, Per (16)
Kataja, Vesa (39) (45)
Knight, Julia A (5) (6)
Kristensen, Vessela N (46) (47) (48)
Lindström, Sara (2) (52)
Mannermaa, Arto (39) (40)
Marme, Federik (18) (55)
Milne, Roger L (7) (35)
Nielsen, Sune F (13) (61)
Nordestgaard, Børge G (13) (14) (61)
Phillips, Kelly-Anne (7) (63) (64)
Pylkäs, Katri (65) (66)
Winqvist, Robert (65) (66)
Zheng, Wei (76)

Affiliations

Organisations

  1. (1) University of Cambridge, grid.5335.0
  2. (2) Harvard University, grid.38142.3c
  3. (3) Cambridge Experimental Cancer Medicine Centre, Cambridge, UK
  4. (4) Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  5. (5) Mount Sinai Hospital, grid.416166.2
  6. (6) University of Toronto, grid.17063.33
  7. (7) University of Melbourne, grid.1008.9
  8. (8) German Cancer Research Center, grid.7497.d
  9. (9) Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain
  10. (10) Spanish National Cancer Research Centre, grid.7719.8
  11. (11) National Cancer Institute, grid.48336.3a
  12. (12) Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  13. (13) Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  14. (14) University of Copenhagen, grid.5254.6, KU
  15. (15) European Institute of Oncology, grid.15667.33
  16. (16) Karolinska Institute, grid.4714.6
  17. (17) Antoni van Leeuwenhoek Hospital, grid.430814.a
  18. (18) Heidelberg University, grid.7700.0
  19. (19) Cancer Research UK Cambridge Institute, grid.470869.4
  20. (20) University of Pisa, grid.5395.a
  21. (21) University Cancer Center Hamburg, grid.412315.0
  22. (22) Mayo Clinic, grid.66875.3a
  23. (23) University of Sheffield, grid.11835.3e
  24. (24) Pomeranian Medical University, grid.107950.a
  25. (25) Leiden University Medical Center, grid.10419.3d
  26. (26) American Cancer Society, grid.422418.9
  27. (27) University of Southampton, grid.5491.9
  28. (28) Institute of Human Genetics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  29. (29) University of Manchester, grid.5379.8
  30. (30) University of California, Los Angeles, grid.19006.3e
  31. (31) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  32. (32) University of Edinburgh, grid.4305.2
  33. (33) University Medical Center Hamburg-Eppendorf, grid.13648.38
  34. (34) Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  35. (35) Cancer Council Victoria, grid.3263.4
  36. (36) Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
  37. (37) University of Southern California, grid.42505.36
  38. (38) University of Massachusetts Amherst, grid.266683.f
  39. (39) University of Eastern Finland, grid.9668.1
  40. (40) Kuopio University Hospital, grid.410705.7
  41. (41) University of Warwick, grid.7372.1
  42. (42) Krebsregister Saarland, grid.482902.5
  43. (43) Erasmus University Medical Center, grid.5645.2
  44. (44) Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland
  45. (45) Central Finland Health Care District, grid.460356.2
  46. (46) Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
  47. (47) Oslo University Hospital, grid.55325.34
  48. (48) University of Oslo, grid.5510.1
  49. (49) Flanders Institute for Biotechnology, grid.11486.3a
  50. (50) KU Leuven, grid.5596.f
  51. (51) University of Hawaii at Manoa, grid.410445.0
  52. (52) University of Washington, grid.34477.33
  53. (53) Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center – Oncology Institute, Warsaw, Poland
  54. (54) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  55. (55) National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
  56. (56) The Alfred Hospital, grid.1623.6
  57. (57) Hospital Monte Naranco, grid.414858.4
  58. (58) University Health Network, grid.231844.8
  59. (59) Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  60. (60) Universitair Ziekenhuis Leuven, grid.410569.f
  61. (61) Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  62. (62) IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy
  63. (63) Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Australia
  64. (64) Peter MacCallum Cancer Centre, grid.1055.1
  65. (65) Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland
  66. (66) University of Oulu, grid.10858.34
  67. (67) Institute of Cancer Research, grid.18886.3f
  68. (68) Städtisches Klinikum Karlsruhe, grid.419594.4
  69. (69) King's College London, grid.13097.3c
  70. (70) Case Western Reserve University, grid.67105.35
  71. (71) University of Oxford, grid.4991.5
  72. (72) Klinikum Mittelbaden, grid.506801.a
  73. (73) Hospital Universitario La Paz, grid.81821.32
  74. (74) QIMR Berghofer Medical Research Institute, grid.1049.c
  75. (75) Hannover Medical School, grid.10423.34
  76. (76) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA and

Description

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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Times Cited: 15

Field Citation Ratio (FCR): 5.43

Relative Citation ratio (RCR): 0.96

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