Article open access publication

Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study

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

Volume 45, 3, 2016

DOI:10.1093/ije/dyw158, Dimensions: pub.1059676749, PMC: PMC5644573, PMID: 27401727,

Authors

Rossing, Mary Anne (13) (14)
Edwards, Robert P (22) (23)
Heitz, Florian (25) (26)
Kjær, Susanne (27) (28)
Høgdall, Estrid (27) (29)
Giles, Graham G (32) (33) (34)
Milne, Roger L (33) (34)
Wu, Xifeng (35)
Salvesen, Helga B (42) (43)
Kopperud, Reidun K (42) (43)
Bjorge, Line (42) (43)
Le, Nhu D (47)
Campbell, Ian (34) (54)

Affiliations

Organisations

  1. (1) University of Queensland, grid.1003.2
  2. (2) QIMR Berghofer Medical Research Institute, grid.1049.c
  3. (3) Baylor College of Medicine, grid.39382.33
  4. (4) University of Cambridge, grid.5335.0
  5. (5) University of Michigan, grid.214458.e
  6. (6) University of Southern California, grid.42505.36
  7. (7) Vanderbilt University, grid.152326.1
  8. (8) University of California, Los Angeles, grid.19006.3e
  9. (9) University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen Nuremberg, Erlangen, Germany
  10. (10) Flanders Institute for Biotechnology, grid.11486.3a
  11. (11) KU Leuven, grid.5596.f
  12. (12) Universitair Ziekenhuis Leuven, grid.410569.f
  13. (13) University of Washington, grid.34477.33
  14. (14) Fred Hutchinson Cancer Research Center, grid.270240.3
  15. (15) Dartmouth College, grid.254880.3
  16. (16) German Cancer Research Center, grid.7497.d
  17. (17) Roswell Park Cancer Institute, grid.240614.5
  18. (18) Cedars-Sinai Medical Center, grid.50956.3f
  19. (19) University of Hawaii at Manoa, grid.410445.0
  20. (20) Hannover Medical School, grid.10423.34
  21. (21) Helsinki University Central Hospital, grid.15485.3d
  22. (22) University of Pittsburgh Cancer Institute, grid.478063.e
  23. (23) University of Pittsburgh, grid.21925.3d
  24. (24) The University of Texas Health Science Center at Houston, grid.267308.8
  25. (25) Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
  26. (26) Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/ Evang. Huyssens-Stiftung/ Knappschaft GmbH, Essen, Germany
  27. (27) Danish Cancer Society, grid.417390.8
  28. (28) Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  29. (29) University of Copenhagen, grid.5254.6, KU
  30. (30) Mayo Clinic, grid.66875.3a
  31. (31) University of Kansas Medical Center, grid.412016.0
  32. (32) Monash University, grid.1002.3
  33. (33) Cancer Council Victoria, grid.3263.4
  34. (34) University of Melbourne, grid.1008.9
  35. (35) The University of Texas MD Anderson Cancer Center, grid.240145.6
  36. (36) Texas Southern University, grid.264771.1
  37. (37) Memorial Sloan Kettering Cancer Center, grid.51462.34
  38. (38) Duke University, grid.26009.3d
  39. (39) Duke University Hospital, grid.189509.c
  40. (40) Brigham and Women's Hospital, grid.62560.37
  41. (41) Rutgers, The State University of New Jersey, grid.430387.b
  42. (42) Haukeland University Hospital, grid.412008.f
  43. (43) University of Bergen, grid.7914.b
  44. (44) Radboud University Nijmegen Medical Centre, grid.10417.33
  45. (45) Oregon Health & Science University, grid.5288.7
  46. (46) University of New Mexico, grid.266832.b
  47. (47) BC Cancer Agency, grid.248762.d
  48. (48) University of British Columbia, grid.17091.3e
  49. (49) Simon Fraser University, grid.61971.38
  50. (50) Medical University of South Carolina, grid.259828.c
  51. (51) Pomeranian Medical University, grid.107950.a
  52. (52) National Cancer Institute, grid.48336.3a
  53. (53) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  54. (54) Peter MacCallum Cancer Centre, grid.1055.1
  55. (55) University of Southampton, grid.5491.9
  56. (56) Beatson West of Scotland Cancer Centre, grid.422301.6
  57. (57) Glasgow Royal Infirmary, grid.411714.6
  58. (58) Stanford University, grid.168010.e
  59. (59) University of Toronto, grid.17063.33
  60. (60) Moffitt Cancer Center, grid.468198.a
  61. (61) Yale University, grid.47100.32
  62. (62) Public Health Ontario, grid.415400.4
  63. (63) University of California, Irvine, grid.266093.8
  64. (64) University College London, grid.83440.3b

Description

BACKGROUND: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC. METHODS: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects meta-analysis. RESULTS: Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low-grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81). CONCLUSIONS: Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence.

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Times Cited: 40

Field Citation Ratio (FCR): 13.31

Relative Citation ratio (RCR): 2.33

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