Article open access publication

Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA

Human Genetics, Springer Nature, ISSN 0340-6717

Volume 133, 5, 2014

DOI:10.1007/s00439-013-1383-3, Dimensions: pub.1032712467, PMC: PMC4063682, PMID: 24190013,

Authors

Lu, Yi (6)
Rossing, Mary Anne (15) (16)
Butzow, Ralf (24) (25)
Edwards, Robert P. (26) (27)
du Bois, Andreas (29) (30)
Heitz, Florian (29) (30)
Harter, Philipp (29) (30)
Kjær, Susanne (32) (33)
Høgdall, Estrid (32) (34)
Giles, Graham G (37) (38)
Baglietto, Laura (37) (38)
Severi, Gianluca (37) (38)
Wu, Xifeng (40)
Lu, Karen (40)
Cramer, Daniel W. (44) (45)
Terry, Kathryn L (44) (45)
Poole, Elizabeth M (45) (46)
Wik, Elisabeth (48) (49)
Salvesen, Helga B. (48) (49)
Bjorge, Line (48) (49)
Halle, Mari K. (48) (49)
Aben, Katja K H (50) (51)
Dicks, Ed (58)
Campbell, Ian G (7) (38)
Wu, Anna H (68)
Pike, Malcolm C (41) (68)
Cook, Linda S. (2) (3) (69)

* Corresponding author

Affiliations

Organisations

  1. (1) BC Cancer Agency, grid.248762.d
  2. (2) Alberta Health Services, grid.413574.0
  3. (3) University of Calgary, grid.22072.35
  4. (4) Moffitt Cancer Center, grid.468198.a
  5. (5) University of British Columbia, grid.17091.3e
  6. (6) QIMR Berghofer Medical Research Institute, grid.1049.c
  7. (7) Peter MacCallum Cancer Centre, grid.1055.1
  8. (8) Department of Gynecology and Obstetrics, Comprehensive Cancer Center, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
  9. (9) University of Erlangen-Nuremberg, grid.5330.5
  10. (10) University of California, Los Angeles, grid.19006.3e
  11. (11) Flanders Institute for Biotechnology, grid.11486.3a
  12. (12) KU Leuven, grid.5596.f
  13. (13) Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, Leuven Cancer Institute, Louvain, Belgium
  14. (14) Dartmouth College, grid.254880.3
  15. (15) Fred Hutchinson Cancer Research Center, grid.270240.3
  16. (16) University of Washington, grid.34477.33
  17. (17) German Cancer Research Center, grid.7497.d
  18. (18) Roswell Park Cancer Institute, grid.240614.5
  19. (19) University of Hawaii at Manoa, grid.410445.0
  20. (20) Cedars-Sinai Medical Center, grid.50956.3f
  21. (21) Department of Obstetrics and Gynaecology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany
  22. (22) Hannover Medical School, grid.10423.34
  23. (23) Aleksandrov Byelorussian Institute for Oncology and Medical Radiology, Minsk, Belarus
  24. (24) Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
  25. (25) Department of Pathology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
  26. (26) University of Pittsburgh, grid.21925.3d
  27. (27) Women’s Cancer Research Center, Magee-Womens Research Institute, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
  28. (28) The University of Texas Health Science Center at Houston, grid.267308.8
  29. (29) Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
  30. (30) Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens Stiftung/Knappschaft GmbH, Essen, Germany
  31. (31) Institut für Humangenetik, Wiesbaden, Germany
  32. (32) Danish Cancer Society, grid.417390.8
  33. (33) Rigshospitalet, grid.475435.4, Capital Region
  34. (34) University of Copenhagen, grid.5254.6, KU
  35. (35) University of Kansas Medical Center, grid.412016.0
  36. (36) Mayo Clinic, grid.66875.3a
  37. (37) Cancer Council Victoria, grid.3263.4
  38. (38) University of Melbourne, grid.1008.9
  39. (39) Texas Southern University, grid.264771.1
  40. (40) The University of Texas MD Anderson Cancer Center, grid.240145.6
  41. (41) Memorial Sloan Kettering Cancer Center, grid.51462.34
  42. (42) Duke University, grid.26009.3d
  43. (43) Duke University Hospital, grid.189509.c
  44. (44) Brigham and Women's Hospital, grid.62560.37
  45. (45) Harvard University, grid.38142.3c
  46. (46) Channing Division of Network Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
  47. (47) Rutgers, The State University of New Jersey, grid.430387.b
  48. (48) Haukeland University Hospital, grid.412008.f
  49. (49) University of Bergen, grid.7914.b
  50. (50) Radboud University Nijmegen Medical Centre, grid.10417.33
  51. (51) Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands
  52. (52) Oregon Health & Science University, grid.5288.7
  53. (53) Pomeranian Medical University, grid.107950.a
  54. (54) National Cancer Institute, grid.48336.3a
  55. (55) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  56. (56) Breast Cancer Now, grid.458394.7
  57. (57) Institute of Cancer Research, grid.18886.3f
  58. (58) University of Cambridge, grid.5335.0
  59. (59) Faculty of Medicine, University Hospital Southampton, University of Southampton, Southampton, UK
  60. (60) Stanford University, grid.168010.e
  61. (61) Imperial College London, grid.7445.2
  62. (62) Beatson West of Scotland Cancer Centre, grid.422301.6
  63. (63) Yale University, grid.47100.32
  64. (64) Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
  65. (65) University of Toronto, grid.17063.33
  66. (66) University of California, Irvine, grid.266093.8
  67. (67) University College London, grid.83440.3b
  68. (68) University of Southern California, grid.42505.36
  69. (69) University of New Mexico, grid.266832.b
  70. (70) Simon Fraser University, grid.61971.38

Description

Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.

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University of Copenhagen

Danish Open Access Indicator

2014: Unused

Research area: Medicine

Danish Bibliometrics Indicator

2014: Level 1

Research area: Medicine

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Times Cited: 18

Field Citation Ratio (FCR): 2.75

Relative Citation ratio (RCR): 0.66

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Green, Accepted