Article open access publication

Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Cancer Discovery, American Association for Cancer Research (AACR), ISSN 2159-8274

Volume 6, 9, 2016

DOI:10.1158/2159-8290.cd-15-1227, Dimensions: pub.1001325962, PMC: PMC5010513, PMID: 27432226,

Authors

BioResource, APCB (19) (20)
Neal, David E. (1) (39)
Høgdall, Estrid (49) (50)
Heitz, Florian (53) (54)
Hamdy, Freddie C. (57) (58)
Giles, Graham G (52) (59) (60)
Salvesen, Helga B. (65) (66)
Brenner, Hermann (10) (67)
Brauch, Hiltrud (10) (68) (69)
Campbell, Ian (60) (71)
Stanford, Janet L (73) (74)
Knight, Julia A. (82) (83)
Muir, Kenneth (89) (90)
Aly, Markus (13) (97)
Rossing, Mary Anne (73) (74)
Le, Nhu D. (104)
Orr, Nick (3)
Pashayan, Nora (1) (11)
Guénel, Pascal (106) (107)
Wang, Qin (1)
Cai, Qiuyin (110)
Li, Qiyuan (111) (112)
Schmutzler, Rita K. (113) (114)
Milne, Roger L. (52) (60)
Lee, Soo Chin (117) (118)
Teo, Soo-Hwang (119) (120)
Bojesen, Stig E. (24) (49)
Kjær, Susanne (50) (122)
Dörk, Thilo (102)
Kosma, Veli-Matti (127) (128)
Kristensen, Vessela (129) (130) (131)
Zheng, Wei (110)
Gao, Yu-Tang (133)
Freedman, Matthew L (112) (134)
Hall, Per (13)
Eeles, Rosalind (3) (136)

Affiliations

Organisations

  1. (1) University of Cambridge, grid.5335.0
  2. (2) QIMR Berghofer Medical Research Institute, grid.1049.c
  3. (3) Institute of Cancer Research, grid.18886.3f
  4. (4) University of Southern California, grid.42505.36
  5. (5) Harvard University, grid.38142.3c
  6. (6) University of Sydney, grid.1013.3
  7. (7) Division of Urologic Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts
  8. (8) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  9. (9) University of Surrey, grid.5475.3
  10. (10) German Cancer Research Center, grid.7497.d
  11. (11) University College London, grid.83440.3b
  12. (12) Stanford University, grid.168010.e
  13. (13) Karolinska Institute, grid.4714.6
  14. (14) Moffitt Cancer Center, grid.468198.a
  15. (15) Portuguese Oncology Institute, grid.418711.a
  16. (16) University of Sheffield, grid.11835.3e
  17. (17) Spanish National Cancer Research Centre, grid.7719.8
  18. (18) A list of members from the Australian Ovarian Cancer Study (AOCS) Study Group and the Australian Cancer Study (Ovarian Cancer) is provided in the Acknowledgments
  19. (19) A list of members from the Australian Prostate Cancer BioResource (APCB) BioResource is provided in the Acknowledgments
  20. (20) Queensland University of Technology, grid.1024.7
  21. (21) University of California, Irvine, grid.266093.8
  22. (22) University Hospital Erlangen, Institute of Human Genetics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
  23. (23) Cedars-Sinai Medical Center, grid.50956.3f
  24. (24) Herlev Hospital, grid.411900.d, Capital Region
  25. (25) University of Helsinki, grid.7737.4
  26. (26) The Alfred Hospital, grid.1623.6
  27. (27) University of Michigan, grid.214458.e
  28. (28) Mayo Clinic, grid.66875.3a
  29. (29) Pomeranian Medical University, grid.107950.a
  30. (30) Medical University of Sofia, grid.410563.5
  31. (31) Krebsregister Saarland, grid.482902.5
  32. (32) University Hospital Ulm, grid.410712.1
  33. (33) Roswell Park Cancer Institute, grid.240614.5
  34. (34) The Juliane Marie Centre, Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  35. (35) University of Utah, grid.223827.e
  36. (36) Seoul National University, grid.31501.36
  37. (37) McGill University and Génome Québec Innovation Centre, grid.411640.6
  38. (38) Brigham and Women's Hospital, grid.62560.37
  39. (39) Cancer Research UK Cambridge Institute, grid.470869.4
  40. (40) University of Southampton, grid.5491.9
  41. (41) University Medical Center Hamburg-Eppendorf, grid.13648.38
  42. (42) Vanderbilt University Medical Center, grid.412807.8
  43. (43) Memorial Sloan Kettering Cancer Center, grid.51462.34
  44. (44) National Centre of Scientific Research Demokritos, grid.6083.d
  45. (45) King's College London, grid.13097.3c
  46. (46) Rutgers, The State University of New Jersey, grid.430387.b
  47. (47) Bashkir State University, grid.77269.3d
  48. (48) Institute of Biochemistry and Genetics of Ufa Scientific Centre, grid.429129.5
  49. (49) University of Copenhagen, grid.5254.6, KU
  50. (50) Danish Cancer Society, grid.417390.8
  51. (51) Tianjin Medical University Cancer Institute and Hospital, grid.411918.4
  52. (52) Cancer Council Victoria, grid.3263.4
  53. (53) Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
  54. (54) Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens Stiftung/Knappschaft GmbH, Essen, Germany
  55. (55) University of Pittsburgh, grid.21925.3d
  56. (56) University of Pittsburgh Cancer Institute, grid.478063.e
  57. (57) Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, UK
  58. (58) University of Oxford, grid.4991.5
  59. (59) Monash University, grid.1002.3
  60. (60) University of Melbourne, grid.1008.9
  61. (61) Skåne University Hospital, grid.411843.b
  62. (62) Universitair Ziekenhuis Leuven, grid.410569.f
  63. (63) Klinikum Mittelbaden, grid.506801.a
  64. (64) Yale University, grid.47100.32
  65. (65) Haukeland University Hospital, grid.412008.f
  66. (66) University of Bergen, grid.7914.b
  67. (67) University Hospital Heidelberg, grid.5253.1
  68. (68) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  69. (69) University of Tübingen, grid.10392.39
  70. (70) University of Glasgow, grid.8756.c
  71. (71) Peter MacCallum Cancer Centre, grid.1055.1
  72. (72) Department of Gynaecologic Oncology, Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, Leuven, Belgium
  73. (73) Fred Hutchinson Cancer Research Center, grid.270240.3
  74. (74) University of Washington, grid.34477.33
  75. (75) Dartmouth College, grid.254880.3
  76. (76) University of Bristol, grid.5337.2
  77. (77) Duke University, grid.26009.3d
  78. (78) Duke University Hospital, grid.189509.c
  79. (79) Tampere University, grid.502801.e
  80. (80) University of Turku, grid.1374.1
  81. (81) National Institutes of Health, grid.94365.3d
  82. (82) Mount Sinai Hospital, grid.416166.2
  83. (83) University of Toronto, grid.17063.33
  84. (84) London School of Hygiene & Tropical Medicine, grid.8991.9
  85. (85) The University of Texas MD Anderson Cancer Center, grid.240145.6
  86. (86) Rechts der Isar Hospital, grid.15474.33
  87. (87) A list of members from the Kathleen Cuningham Foundation Consortium for research into Familial Breast cancer (kConFab) Investigators is provided in the Acknowledgments
  88. (88) Kyushu University, grid.177174.3
  89. (89) University of Manchester, grid.5379.8
  90. (90) University of Warwick, grid.7372.1
  91. (91) Radboud University Nijmegen Medical Centre, grid.10417.33
  92. (92) University of New Mexico, grid.266832.b
  93. (93) George E. Wahlen Department of VA Medical Center, grid.413886.0
  94. (94) Erasmus University Medical Center, grid.5645.2
  95. (95) University of Porto, grid.5808.5
  96. (96) Antoni van Leeuwenhoek Hospital, grid.430814.a
  97. (97) Danderyds sjukhus, grid.412154.7
  98. (98) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  99. (99) KU Leuven, grid.5596.f
  100. (100) Meharry Medical College, grid.259870.1
  101. (101) Cancer Center and Department of Surgery, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
  102. (102) Hannover Medical School, grid.10423.34
  103. (103) A list of members from the Norwegian Breast Cancer Study (NBCS) Investigators is provided in the Acknowledgments
  104. (104) BC Cancer Agency, grid.248762.d
  105. (105) FIRC Institute of Molecular Oncology, grid.7678.e
  106. (106) French Institute of Health and Medical Research, grid.7429.8
  107. (107) University of Paris-Sud, grid.5842.b
  108. (108) International Agency For Research On Cancer, grid.17703.32
  109. (109) Leiden University Medical Center, grid.10419.3d
  110. (110) Vanderbilt University, grid.152326.1
  111. (111) Xiamen University, grid.12955.3a
  112. (112) Dana-Farber Cancer Institute, grid.65499.37
  113. (113) University Hospital Cologne, grid.411097.a
  114. (114) University of Cologne, grid.6190.e
  115. (115) University of Oulu, grid.10858.34
  116. (116) The University of Texas Health Science Center at Houston, grid.267308.8
  117. (117) National University Health System, grid.410759.e
  118. (118) National University of Singapore, grid.4280.e
  119. (119) Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia
  120. (120) University of Malaya Cancer Research Institute, University Malaya Medical Centre, University of Malaya, Kuala Lumpur, Malaysia
  121. (121) American Cancer Society, grid.422418.9
  122. (122) Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  123. (123) Oregon Health & Science University, grid.5288.7
  124. (124) A list of members from the GENICA Network is provided in the Acknowledgments
  125. (125) A list of members from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium is provided in the Acknowledgments
  126. (126) Ruhr University Bochum, grid.5570.7
  127. (127) Kuopio University Hospital, grid.410705.7
  128. (128) University of Eastern Finland, grid.9668.1
  129. (129) Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
  130. (130) K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  131. (131) Oslo University Hospital, grid.55325.34
  132. (132) Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
  133. (133) Shanghai Cancer Institute, grid.419087.3
  134. (134) Broad Institute, grid.66859.34
  135. (135) Laval University, grid.23856.3a
  136. (136) Royal Marsden National Health Service (NHS) Foundation Trust, London and Sutton, UK

Description

Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

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Times Cited: 75

Field Citation Ratio (FCR): 19.53

Relative Citation ratio (RCR): 3.61

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