Article open access publication

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Human Molecular Genetics, Oxford University Press (OUP), ISSN 1460-2083

Volume 24, 20, 2015

DOI:10.1093/hmg/ddv306, Dimensions: pub.1059645626, PMC: PMC4581608, PMID: 26231222,

Authors

Lu, Yi (1)
Rossing, Mary Anne (12) (13)
Goodman, Marc T (16) (17)
Edwards, Robert P. (25) (26)
Høgdall, Estrid (29) (30)
Giles, Graham G (31) (32) (33)
Kjaer, Susanne K. (30) (34)
Wu, Xifeng (35)
Dao, Fanny (38)
Terry, Kathryn L (39) (40)
Missmer, Stacey (40) (41)
Bjorge, Line (42) (43)
Salvesen, Helga B. (42) (43)
Bischof, Katharina (42) (43)
Aben, Katja K H (44) (45)
Le, Nhu D. (51)
Anton-Culver, Hoda (35) (61)
Wu, Anna H (63)
Poole, Elizabeth M (40) (41)
Morgan, Terry K. (23) (70)
Pearce, Celeste L. (63) (76)
Pharoah, Paul D P (55) (77)

Affiliations

Organisations

  1. (1) Statistical Genetics,
  2. (2) Molecular Cancer Epidemiology,
  3. (3) Queensland University of Technology, grid.1024.7
  4. (4) University of Liverpool, grid.10025.36
  5. (5) Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics and
  6. (6) University of California, Los Angeles, grid.19006.3e
  7. (7) Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen Nuremberg, Universitaetsstrasse 21-23, 91054 Erlangen, Germany,
  8. (8) Flanders Institute for Biotechnology, grid.11486.3a
  9. (9) KU Leuven, grid.5596.f
  10. (10) Universitair Ziekenhuis Leuven, grid.410569.f
  11. (11) Dartmouth College, grid.254880.3
  12. (12) University of Washington, grid.34477.33
  13. (13) Fred Hutchinson Cancer Research Center, grid.270240.3
  14. (14) German Cancer Research Center, grid.7497.d
  15. (15) University of Ulm, grid.6582.9
  16. (16) Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute and
  17. (17) Cedars-Sinai Medical Center, grid.50956.3f
  18. (18) Radiation Oncology Research Unit,
  19. (19) Gynaecology Research Unit and
  20. (20) Friedrich Schiller University Jena, grid.9613.d
  21. (21) Hannover Medical School, grid.10423.34
  22. (22) N.N. Alexandrov National Cancer Centre, grid.477553.7
  23. (23) Department of Pathology and
  24. (24) Helsinki University Central Hospital, grid.15485.3d
  25. (25) University of Pittsburgh, grid.21925.3d
  26. (26) University of Pittsburgh Cancer Institute, grid.478063.e
  27. (27) Roswell Park Cancer Institute, grid.240614.5
  28. (28) The University of Texas Health Science Center at Houston, grid.267308.8
  29. (29) Herlev Hospital, grid.411900.d, Capital Region
  30. (30) Danish Cancer Society, grid.417390.8
  31. (31) Monash University, grid.1002.3
  32. (32) University of Melbourne, grid.1008.9
  33. (33) Cancer Council Victoria, grid.3263.4
  34. (34) Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark,
  35. (35) Department of Epidemiology and
  36. (36) Texas Southern University, grid.264771.1
  37. (37) The University of Texas MD Anderson Cancer Center, grid.240145.6
  38. (38) Gynecology Service, Department of Surgery and
  39. (39) Brigham and Women's Hospital, grid.62560.37
  40. (40) Harvard University, grid.38142.3c
  41. (41) Channing Division of Network Medicine, Department of Medicine and
  42. (42) Haukeland University Hospital, grid.412008.f
  43. (43) University of Bergen, grid.7914.b
  44. (44) Netherlands Comprehensive Cancer Organisation, grid.470266.1
  45. (45) Radboud University Nijmegen Medical Centre, grid.10417.33
  46. (46) Canada's Michael Smith Genome Sciences Centre and
  47. (47) Simon Fraser University, grid.61971.38
  48. (48) Memorial Sloan Kettering Cancer Center, grid.51462.34
  49. (49) Stanford University, grid.168010.e
  50. (50) University of New Mexico, grid.266832.b
  51. (51) BC Cancer Agency, grid.248762.d
  52. (52) University of British Columbia, grid.17091.3e
  53. (53) Pomeranian Medical University, grid.107950.a
  54. (54) Rzeszów University, grid.13856.39
  55. (55) Department of Oncology and
  56. (56) National Cancer Institute, grid.48336.3a
  57. (57) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  58. (58) Public Health Ontario, grid.415400.4
  59. (59) University of Toronto, grid.17063.33
  60. (60) Moffitt Cancer Center, grid.468198.a
  61. (61) University of California, Irvine, grid.266093.8
  62. (62) University of Southampton, grid.5491.9
  63. (63) University of Southern California, grid.42505.36
  64. (64) University College London, grid.83440.3b
  65. (65) Department of Obstetrics, Gynecology and Oncology, IInd Faculty of Medicine, Warsaw Medical University and Brodnowski Hospital, Warsaw, Poland,
  66. (66) Division of Experimental Pathology, Department of Laboratory Medicine and Pathology,
  67. (67) University of Kansas, grid.266515.3
  68. (68) Division of Biomedical Statistics and Informatics, Department of Health Sciences Research and
  69. (69) Rutgers, The State University of New Jersey, grid.430387.b
  70. (70) Oregon Health & Science University, grid.5288.7
  71. (71) Yale University, grid.47100.32
  72. (72) Mayo Clinic, grid.66875.3a
  73. (73) Department of Community and Family Medicine and
  74. (74) Duke University, grid.26009.3d
  75. (75) Population Health Department,
  76. (76) University of Michigan, grid.214458.e
  77. (77) University of Cambridge, grid.5335.0
  78. (78) Molecular Epidemiology and
  79. (79) University of Oxford, grid.4991.5
  80. (80) QIMR Berghofer Medical Research Institute, grid.1049.c

Description

Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.

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Times Cited: 38

Field Citation Ratio (FCR): 6.5

Relative Citation ratio (RCR): 2.2

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