Article open access publication

Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study

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

Volume 45, 5, 2016

DOI:10.1093/ije/dyw207, Dimensions: pub.1059676785, PMC: PMC5100621, PMID: 27594614,

Authors

Ong, Jue-Sheng (1) (2)
Lu, Yi (2)
Edwards, Robert P (17) (18)
Høgdall, Estrid (21) (22)
Kjaer, Susanne K (22) (23)
Wu, Xifeng (25)
Dao, Fanny (27)
Stampfer, Meir (28) (29)
Bjorge, Line (30) (31)
Salvesen, Helga B (30) (31)
Kopperud, Reidun K (30) (31)
Bischof, Katharina (30) (31)
Aben, Katja K H (32) (33)
Le, Nhu D (35)
Wu, Anna H (50)
Poole, Elizabeth M (28) (29)
Pearce, Celeste L (50) (61)

Affiliations

Organisations

  1. (1) University of Queensland, grid.1003.2
  2. (2) QIMR Berghofer Medical Research Institute, grid.1049.c
  3. (3) Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles,
  4. (4) University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen—EMN, 91054 Erlangen, Germany,
  5. (5) Flanders Institute for Biotechnology, grid.11486.3a
  6. (6) KU Leuven, grid.5596.f
  7. (7) Universitair Ziekenhuis Leuven, grid.410569.f
  8. (8) Fred Hutchinson Cancer Research Center, grid.270240.3
  9. (9) University of Washington, grid.34477.33
  10. (10) German Cancer Research Center, grid.7497.d
  11. (11) University of Ulm, grid.6582.9
  12. (12) Cedars-Sinai Medical Center, grid.50956.3f
  13. (13) Hannover Medical School, grid.10423.34
  14. (14) Friedrich Schiller University Jena, grid.9613.d
  15. (15) N.N. Alexandrov National Cancer Centre, grid.477553.7
  16. (16) Helsinki University Central Hospital, grid.15485.3d
  17. (17) University of Pittsburgh Cancer Institute, grid.478063.e
  18. (18) University of Pittsburgh, grid.21925.3d
  19. (19) Roswell Park Cancer Institute, grid.240614.5
  20. (20) The University of Texas Health Science Center at Houston, grid.267308.8
  21. (21) University of Copenhagen, grid.5254.6, KU
  22. (22) Danish Cancer Society, grid.417390.8
  23. (23) Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark,
  24. (24) Cancer Council Victoria, grid.3263.4
  25. (25) The University of Texas MD Anderson Cancer Center, grid.240145.6
  26. (26) Texas Southern University, grid.264771.1
  27. (27) Memorial Sloan Kettering Cancer Center, grid.51462.34
  28. (28) Brigham and Women's Hospital, grid.62560.37
  29. (29) Harvard University, grid.38142.3c
  30. (30) Haukeland University Hospital, grid.412008.f
  31. (31) University of Bergen, grid.7914.b
  32. (32) Netherlands Comprehensive Cancer Organisation, grid.470266.1
  33. (33) Radboud University Nijmegen Medical Centre, grid.10417.33
  34. (34) Simon Fraser University, grid.61971.38
  35. (35) BC Cancer Agency, grid.248762.d
  36. (36) Stanford University, grid.168010.e
  37. (37) University of New Mexico, grid.266832.b
  38. (38) University of British Columbia, grid.17091.3e
  39. (39) Pomeranian Medical University, grid.107950.a
  40. (40) Rzeszów University, grid.13856.39
  41. (41) University of Cambridge, grid.5335.0
  42. (42) National Cancer Institute, grid.48336.3a
  43. (43) Department of Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland,
  44. (44) Public Health Ontario, grid.415400.4
  45. (45) University of Toronto, grid.17063.33
  46. (46) Moffitt Cancer Center, grid.468198.a
  47. (47) University of California, Irvine, grid.266093.8
  48. (48) University of Southampton, grid.5491.9
  49. (49) Peter MacCallum Cancer Centre, grid.1055.1
  50. (50) University of Southern California, grid.42505.36
  51. (51) University College London, grid.83440.3b
  52. (52) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  53. (53) Department of Obstetrics, Gynaecology and Oncology, IInd Faculty of Medicine, Warsaw Medical University and Brodnowski Hospital, Warsaw, Poland,
  54. (54) Mayo Clinic, grid.66875.3a
  55. (55) University of Kansas, grid.266515.3
  56. (56) Rutgers, The State University of New Jersey, grid.430387.b
  57. (57) Oregon Health & Science University, grid.5288.7
  58. (58) Yale University, grid.47100.32
  59. (59) Duke University Hospital, grid.189509.c
  60. (60) Duke University, grid.26009.3d
  61. (61) University of Michigan, grid.214458.e

Description

BACKGROUND: In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observational studies is inadequate control of confounding. To overcome this problem, we used Mendelian randomization (MR) to evaluate the association between single nucleotide polymorphisms (SNPs) associated with circulating 25-hydroxyvitamin D [25(OH)D] concentration and risk of ovarian cancer. METHODS: We employed SNPs with well-established associations with 25(OH)D concentration as instrumental variables for MR: rs7944926 (DHCR7), rs12794714 (CYP2R1) and rs2282679 (GC). We included 31 719 women of European ancestry (10 065 cases, 21 654 controls) from the Ovarian Cancer Association Consortium, who were genotyped using customized Illumina Infinium iSelect (iCOGS) arrays. A two-sample (summary data) MR approach was used and analyses were performed separately for all ovarian cancer (10 065 cases) and for high-grade serous ovarian cancer (4121 cases). RESULTS: The odds ratio for epithelial ovarian cancer risk (10 065 cases) estimated by combining the individual SNP associations using inverse variance weighting was 1.27 (95% confidence interval: 1.06 to 1.51) per 20 nmol/L decrease in 25(OH)D concentration. The estimated odds ratio for high-grade serous epithelial ovarian cancer (4121 cases) was 1.54 (1.19, 2.01). CONCLUSIONS: Genetically lowered 25-hydroxyvitamin D concentrations were associated with higher ovarian cancer susceptibility in Europeans. These findings suggest that increasing plasma vitamin D levels may reduce risk of ovarian cancer.

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Times Cited: 65

Field Citation Ratio (FCR): 19.04

Relative Citation ratio (RCR): 4.73

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