Article open access publication

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

British Journal of Cancer, Springer Nature, ISSN 0007-0920

Volume 121, 2, 2019

DOI:10.1038/s41416-019-0492-8, Dimensions: pub.1117290986, PMC: PMC6738050, PMID: 31213659,

Authors

Andrulis, Irene L. (12) (13)
Arnold, Norbert (14) (15)
Benitez, Javier (20) (21)
Borde, Julika (24) (25)
Borg, Ake (26)
Campbell, Ian (32) (33)
Eeles, Ros (46)
Evans, D. Gareth (48) (49)
Faivre, Laurence (50) (51)
Friedman, Eitan (53) (54)
Hauke, Jan (23) (24) (25)
Hulick, Peter J. (1) (61)
Jakubowska, Anna (21) (22)
Lesueur, Fabienne (71) (72)
Mebirouk, Noura (71) (72) (73)
Ramus, Susan J. (89) (90)
Teixeira, Manuel R. (99) (100)
Tischkowitz, Marc (3) (102)
Tung, Nadine (103)
Walker, Lisa (107)
Rebbeck, Timothy R. (56) (111)
Huo, Dezheng * (110) (112)

* Corresponding author

Affiliations

Organisations

  1. (1) University of Chicago, grid.170205.1
  2. (2) Antoni van Leeuwenhoek Hospital, grid.430814.a
  3. (3) University of Cambridge, grid.5335.0
  4. (4) Yale University, grid.47100.32
  5. (5) National Cancer Institute, grid.48336.3a
  6. (6) Department of Clinical Genetics, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
  7. (7) Chapel Allerton Hospital, grid.413818.7
  8. (8) National University Hospital of Iceland, grid.410540.4
  9. (9) University of Iceland, grid.14013.37
  10. (10) Great Ormond Street Hospital, grid.420468.c
  11. (11) Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  12. (12) University of Toronto, grid.17063.33
  13. (13) Mount Sinai Hospital, grid.416166.2
  14. (14) Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian Albrechts University Kiel, Kiel, Germany
  15. (15) Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany
  16. (16) The University of Texas MD Anderson Cancer Center, grid.240145.6
  17. (17) University Medical Center Utrecht, grid.7692.a
  18. (18) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  19. (19) University Hospitals of Leicester NHS Trust, grid.269014.8
  20. (20) Spanish National Cancer Research Centre, grid.7719.8
  21. (21) Centre for Biomedical Network Research on Rare Diseases, grid.452372.5
  22. (22) Pomeranian Medical University, grid.107950.a
  23. (23) Centre Léon Bérard, grid.418116.b
  24. (24) University Hospital Cologne, grid.411097.a
  25. (25) University of Cologne, grid.6190.e
  26. (26) Lund University, grid.4514.4
  27. (27) Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
  28. (28) Catalan Institute of Oncology, grid.418701.b
  29. (29) Huntsman Cancer Institute, grid.479969.c
  30. (30) Hospital Clínico San Carlos, grid.411068.a
  31. (31) Azienda Ospedaliera Universitaria Pisana, grid.144189.1
  32. (32) Peter MacCallum Cancer Centre, grid.1055.1
  33. (33) University of Melbourne, grid.1008.9
  34. (34) University of Sydney, grid.1013.3
  35. (35) Hôpital du Saint-Sacrement, grid.416673.1
  36. (36) Columbia University, grid.21729.3f
  37. (37) Ghent University, grid.5342.0
  38. (38) Erasmus University Medical Center, grid.5645.2
  39. (39) Centre Hospitalier Universitaire de Besançon, grid.411158.8
  40. (40) Mayo Clinic, grid.66875.3a
  41. (41) Temple University Health System, grid.412530.1
  42. (42) Institut de Cancérologie de l'Ouest, grid.418191.4
  43. (43) Hospital Universitari Vall d'Hebron, grid.411083.f
  44. (44) University of Pretoria, grid.49697.35
  45. (45) Nottingham University Hospitals NHS Trust, grid.240404.6
  46. (46) Royal Marsden NHS Foundation Trust, grid.5072.0
  47. (47) Leipzig University, grid.9647.c
  48. (48) St Mary's Hospital, grid.416523.7
  49. (49) University of Manchester, grid.5379.8
  50. (50) Centre Georges François Leclerc, grid.418037.9
  51. (51) Centre Hospitalier Regional Universitaire De Dijon, grid.31151.37
  52. (52) Masaryk Memorial Cancer Institute, grid.419466.8
  53. (53) Tel Aviv University, grid.12136.37
  54. (54) Sheba Medical Center, grid.413795.d
  55. (55) University of California, Los Angeles, grid.19006.3e
  56. (56) Dana-Farber Cancer Institute, grid.65499.37
  57. (57) University of Würzburg, grid.8379.5
  58. (58) University of Kansas Medical Center, grid.412016.0
  59. (59) Maastricht University Medical Centre, grid.412966.e
  60. (60) German Cancer Research Center, grid.7497.d
  61. (61) NorthShore University HealthSystem, grid.240372.0
  62. (62) Institute of Oncology NN Petrov, grid.465337.0
  63. (63) Georgetown University Medical Center, grid.411667.3
  64. (64) Guy's and St Thomas' NHS Foundation Trust, grid.420545.2
  65. (65) State Research Institute, Innovative Medicine Center, Vilnius, CA, Lithuania
  66. (66) Vilnius University Hospital Santariskiu Klinikos, grid.426597.b
  67. (67) Stanford University, grid.168010.e
  68. (68) Cedars-Sinai Medical Center, grid.50956.3f
  69. (69) Radboud University Nijmegen Medical Centre, grid.10417.33
  70. (70) Centre Hospitalier Universitaire de Grenoble, grid.410529.b
  71. (71) Genetic Epidemiology of Cancer team, Inserm U900, Paris, France
  72. (72) Institute Curie, grid.418596.7
  73. (73) Mines ParisTech, grid.58140.38
  74. (74) VU University Medical Center, grid.16872.3a
  75. (75) Ludwig Maximilian University of Munich, grid.5252.0
  76. (76) Roswell Park Cancer Institute, grid.240614.5
  77. (77) Istituto Oncologico Veneto, grid.419546.b
  78. (78) City Of Hope National Medical Center, grid.410425.6
  79. (79) Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  80. (80) Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  81. (81) Memorial Sloan Kettering Cancer Center, grid.51462.34
  82. (82) National Institute of Oncology, grid.419617.c
  83. (83) West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Birmingham, UK
  84. (84) Department of Genetics, University Medical Center Groningen, University Groningen, Groningen, The Netherlands
  85. (85) Sapienza University of Rome, grid.7841.a
  86. (86) QIMR Berghofer Medical Research Institute, grid.1049.c
  87. (87) Genome Diagnostics Program, IFOM - the FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy
  88. (88) Medical University of Vienna, grid.22937.3d
  89. (89) The Kinghorn Cancer Centre, grid.410697.d
  90. (90) UNSW Sydney, grid.1005.4
  91. (91) Karolinska Institute, grid.4714.6
  92. (92) Technion – Israel Institute of Technology, grid.6451.6
  93. (93) The Ohio State University, grid.261331.4
  94. (94) University of California, San Francisco, grid.266102.1
  95. (95) Wessex Clinical Genetics Service, University Hospitals Southampton NHS Trust, Southampton, UK
  96. (96) McGill University Health Centre, grid.63984.30
  97. (97) Hannover Medical School, grid.10423.34
  98. (98) Paris Descartes University, grid.10992.33
  99. (99) Portuguese Oncology Institute, grid.418711.a
  100. (100) University of Porto, grid.5808.5
  101. (101) Odense University Hospital, grid.7143.1, Southern Denmark Region
  102. (102) McGill University, grid.14709.3b
  103. (103) Beth Israel Deaconess Medical Center, grid.239395.7
  104. (104) Leiden University Medical Center, grid.10419.3d
  105. (105) VU Amsterdam, grid.12380.38
  106. (106) Hôpital Universitaire Dupuytren, grid.412212.6
  107. (107) Churchill Hospital, grid.415719.f
  108. (108) National Centre of Scientific Research Demokritos, grid.6083.d
  109. (109) University of Utah, grid.223827.e
  110. (110) Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL, USA
  111. (111) Harvard University, grid.38142.3c
  112. (112) Department of Public Health Sciences, University of Chicago, Chicago, IL, USA

Description

BACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.

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