Article open access publication

Identification of six new susceptibility loci for invasive epithelial ovarian cancer

Nature Genetics, Springer Nature, ISSN 1061-4036

Volume 47, 2, 2015

DOI:10.1038/ng.3185, Dimensions: pub.1014636045, PMC: PMC4445140, PMID: 25581431,

Authors

Pejovic, Tanja (4) (5)
Bean, Yukie (4) (5)
Coetzee, Simon (7) (8) (9)
Benitez, Javier (21) (22)
Osorio, Ana (21) (22)
Garcia, Maria Jose (21) (22)
Bernard, Loris (27) (28)
Kirk, Judy (46)
Teixeira, Manuel R (72) (73)
Fasching, Peter A (98) (100)
Lambrechts, Diether (101) (102)
Dicks, Ed (1)
Rossing, Mary Anne (105) (106)
Dörk, Thilo (110)
Modugno, Francesmary (112) (113)
du Bois, Andreas (115) (116)
Heitz, Florian (115) (116)
Schwaab, Ira (117)
Harter, Philipp (115) (116)
Kjaer, Susanne Kruger (120) (121)
Hogdall, Estrid (120) (122)
Teo, Soo-Hwang (123) (125)
Woo, Yin-Ling (124) (125)
Liang, Dong (127)
Wu, Xifeng (96)
Poole, Elizabeth M (131) (132)
Tworoger, Shelley S (131) (132)
Krakstad, Camilla (134) (135)
Salvesen, Helga B (134) (135)
Tangen, Ingvild L (134) (135)
Bjorge, Line (134) (135)
Aben, Katja K H (136) (137)
Kellar, Melissa (4) (5)
Brooks-Wilson, Angela (138) (139)
Le, Nhu D (139)
McNeish, Ian (145)
Paul, James (146)
Carty, Karen (146)
Sieh, Weiva (148)
Zheng, Wei (149)
Gao, Yu-Tang (150)
Rosen, Barry (82) (151)
Chen, Ann (78)
Menon, Usha (155)
Pike, Malcolm C (2) (76)

* Corresponding author

Affiliations

Organisations

  1. (1) University of Cambridge, grid.5335.0
  2. (2) University of Southern California, grid.42505.36
  3. (3) QIMR Berghofer Medical Research Institute, grid.1049.c
  4. (4) Knight Cancer Institute, Portland, Oregon, USA
  5. (5) Oregon Health & Science University, grid.5288.7
  6. (6) Dana-Farber Cancer Institute, grid.65499.37
  7. (7) Center for Cell-Based Therapy, Monte Alegre, Ribeirão Preto, Brazil
  8. (8) Center for Integrative Systems Biology, Monte Alegre, Ribeirão Preto, Brazil
  9. (9) University of Sao Paulo, grid.11899.38
  10. (10) Case Western Reserve University, grid.67105.35
  11. (11) University of Melbourne, grid.1008.9
  12. (12) Columbia University, grid.21729.3f
  13. (13) University of Utah, grid.223827.e
  14. (14) Department of Molecular and Regenerative Medicine, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medical Center, Vilinius University Hospital Santariskiu Clinics, Vilnius, Lithuania, Vilnius University Hospital Santariskiu Clinics, Hematology, Oncology and Transfusion Medicine Center, Vilnius, Lithuania
  15. (15) State Research Institute Centre for Innovative Medicine, grid.493509.2
  16. (16) University of Pretoria, grid.49697.35
  17. (17) City Of Hope National Medical Center, grid.410425.6
  18. (18) Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  19. (19) Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  20. (20) Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  21. (21) Centre for Biomedical Network Research on Rare Diseases, grid.452372.5
  22. (22) Spanish National Cancer Research Centre, grid.7719.8
  23. (23) Maricopa Medical Center, grid.416429.c
  24. (24) Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California, USA
  25. (25) Cook County Health and Hospital System, care of City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California, USA
  26. (26) Fondazione Istituto FIRC (Italian Foundation for Cancer Research) di Oncologia Molecolare (IFOM), Milan, Italy
  27. (27) Cogentech Cancer Genetic Test Laboratory, Milan, Italy
  28. (28) European Institute of Oncology, grid.15667.33
  29. (29) Centro di Riferimento Oncologico, grid.418321.d
  30. (30) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  31. (31) University of Florence, grid.8404.8
  32. (32) Sapienza University of Rome, grid.7841.a
  33. (33) National Centre of Scientific Research Demokritos, grid.6083.d
  34. (34) University of Kansas Medical Center, grid.412016.0
  35. (35) On behalf of the German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC)
  36. (36) University Hospital Cologne, grid.411097.a
  37. (37) University of Cologne, grid.6190.e
  38. (38) Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
  39. (39) Leipzig University, grid.9647.c
  40. (40) Heidelberg University, grid.7700.0
  41. (41) Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon–Centre Léon Bérard, Lyon, France
  42. (42) University of Lyon System, grid.25697.3f
  43. (43) Institute Curie, grid.418596.7
  44. (44) Paris Descartes University, grid.10992.33
  45. (45) Ghent University, grid.5342.0
  46. (46) Australia New Zealand Gynaecological Oncology Group, grid.492287.2
  47. (47) NorthShore University HealthSystem, grid.240372.0
  48. (48) Roswell Park Cancer Institute, grid.240614.5
  49. (49) The Ohio State University, grid.261331.4
  50. (50) Hospital Clínico San Carlos, grid.411068.a
  51. (51) Helsinki University Central Hospital, grid.15485.3d
  52. (52) Erasmus University Medical Center, grid.5645.2
  53. (53) Antoni van Leeuwenhoek Hospital, grid.430814.a
  54. (54) University of Groningen, grid.4830.f
  55. (55) Latvian Biomedical Research and Study Centre, grid.419210.f
  56. (56) Beth Israel Deaconess Medical Center, grid.239395.7
  57. (57) German Cancer Research Center, grid.7497.d
  58. (58) Georgetown University Medical Center, grid.411667.3
  59. (59) McGill University, grid.14709.3b
  60. (60) Institute of Oncology NN Petrov, grid.465337.0
  61. (61) Azienda Ospedaliera Universitaria Pisana, grid.144189.1
  62. (62) Peter MacCallum Cancer Centre, grid.1055.1
  63. (63) National Institute of Oncology, grid.419617.c
  64. (64) Hospital Universitari Vall d'Hebron, grid.411083.f
  65. (65) Institut d'Investigació Biomédica de Bellvitge, grid.418284.3
  66. (66) Institut d'Investigació Biomèdica de Girona, grid.429182.4
  67. (67) Pomeranian Medical University, grid.107950.a
  68. (68) University of Iceland, grid.14013.37
  69. (69) Centre Hospitalier Universitaire de Québec, grid.411081.d
  70. (70) Laval University, grid.23856.3a
  71. (71) Istituto Oncologico Veneto, grid.419546.b
  72. (72) Portuguese Oncology Institute, grid.418711.a
  73. (73) University of Porto, grid.5808.5
  74. (74) Mayo Clinic, grid.66875.3a
  75. (75) National Human Genome Research Institute, grid.280128.1
  76. (76) Memorial Sloan Kettering Cancer Center, grid.51462.34
  77. (77) Medical University of Vienna, grid.22937.3d
  78. (78) Moffitt Cancer Center, grid.468198.a
  79. (79) National Cancer Institute, grid.48336.3a
  80. (80) Carmel Medical Center, grid.413469.d
  81. (81) University Health Network, grid.231844.8
  82. (82) University of Toronto, grid.17063.33
  83. (83) Lunenfeld-Tanenbaum Research Institute, grid.250674.2
  84. (84) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  85. (85) Odense University Hospital, grid.7143.1, Southern Denmark Region
  86. (86) Vejle Sygehus, grid.417271.6, Southern Denmark Region
  87. (87) Rebecca Sieff Hospital, grid.415739.d
  88. (88) Sheba Medical Center, grid.413795.d
  89. (89) Skåne University Hospital, grid.411843.b
  90. (90) Karolinska University Hospital, grid.24381.3c
  91. (91) Sahlgrenska University Hospital, grid.1649.a
  92. (92) Linköping University, grid.5640.7
  93. (93) University of Chicago Medical Center, grid.412578.d
  94. (94) University of California, San Francisco, grid.266102.1
  95. (95) University of Pennsylvania, grid.25879.31
  96. (96) The University of Texas MD Anderson Cancer Center, grid.240145.6
  97. (97) Cedars-Sinai Medical Center, grid.50956.3f
  98. (98) Department of Obstetrics and Gynecology, Erlangen University Hospital, University of Erlangen-Nuremberg, Erlangen, Germany
  99. (99) University of Erlangen-Nuremberg, grid.5330.5
  100. (100) University of California, Los Angeles, grid.19006.3e
  101. (101) Flanders Institute for Biotechnology, grid.11486.3a
  102. (102) KU Leuven, grid.5596.f
  103. (103) Universitair Ziekenhuis Leuven, grid.410569.f
  104. (104) Dartmouth College, grid.254880.3
  105. (105) Fred Hutchinson Cancer Research Center, grid.270240.3
  106. (106) University of Washington, grid.34477.33
  107. (107) University of Ulm, grid.6582.9
  108. (108) University of Hawaii at Manoa, grid.410445.0
  109. (109) Department of Gynecology, Jena University Hospital–Friedrich Schiller University, Jena, Germany
  110. (110) Hannover Medical School, grid.10423.34
  111. (111) Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N., Minsk, Belarus
  112. (112) University of Pittsburgh Cancer Institute, grid.478063.e
  113. (113) University of Pittsburgh, grid.21925.3d
  114. (114) The University of Texas Health Science Center at Houston, grid.267308.8
  115. (115) Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
  116. (116) Kliniken Essen-Mitte, grid.461714.1
  117. (117) Institut für Humangenetik Wiesbaden, Wiesbaden, Germany
  118. (118) Kyushu University, grid.177174.3
  119. (119) Aichi Cancer Center, grid.410800.d
  120. (120) Danish Cancer Society, grid.417390.8
  121. (121) Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  122. (122) University of Copenhagen, grid.5254.6, KU
  123. (123) Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia
  124. (124) Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia
  125. (125) University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia
  126. (126) Cancer Council Victoria, grid.3263.4
  127. (127) Texas Southern University, grid.264771.1
  128. (128) Duke University Hospital, grid.189509.c
  129. (129) Duke University, grid.26009.3d
  130. (130) University of Florida, grid.15276.37
  131. (131) Harvard University, grid.38142.3c
  132. (132) Brigham and Women's Hospital, grid.62560.37
  133. (133) Rutgers, The State University of New Jersey, grid.430387.b
  134. (134) Haukeland University Hospital, grid.412008.f
  135. (135) University of Bergen, grid.7914.b
  136. (136) Radboud University Nijmegen Medical Centre, grid.10417.33
  137. (137) Comprehensive Cancer Center The Netherlands, Utrecht, the Netherlands
  138. (138) Simon Fraser University, grid.61971.38
  139. (139) BC Cancer Agency, grid.248762.d
  140. (140) Medical University of South Carolina, grid.259828.c
  141. (141) University of New Mexico, grid.266832.b
  142. (142) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  143. (143) Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  144. (144) Princess Anne Hospital, grid.415216.5
  145. (145) University of Glasgow, grid.8756.c
  146. (146) Cancer Research UK Clinical Trials Unit, grid.470294.c
  147. (147) Glasgow Royal Infirmary, grid.411714.6
  148. (148) Stanford University, grid.168010.e
  149. (149) Vanderbilt University, grid.152326.1
  150. (150) Shanghai Cancer Institute, grid.419087.3
  151. (151) Princess Margaret Cancer Centre, grid.415224.4
  152. (152) Yale University, grid.47100.32
  153. (153) Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
  154. (154) University of California, Irvine, grid.266093.8
  155. (155) Women's Cancer, University College London Elizabeth Garrett Anderson (EGA) Institute for Women's Health, London, UK
  156. (156) Department of Obstetrics, Gynecology and Oncology, 2nd Faculty of Medicine, Warsaw Medical University and Brodnowski Hospital, Warsaw, Poland

Description

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

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2015: Unused

Research area: Medicine

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2015: Level 2

Research area: Medicine

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Times Cited: 153

Field Citation Ratio (FCR): 33.64

Relative Citation ratio (RCR): 6.13

Open Access Info

Green, Accepted