Article open access publication

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

Nature Genetics, Springer Nature, ISSN 1061-4036

Volume 47, 4, 2015

DOI:10.1038/ng.3242, Dimensions: pub.1023494364, PMC: PMC4549775, PMID: 25751625,

Authors

Wang, Qin (1)
Bojesen, Stig E (6) (7)
Ahsan, Habibul (13) (14) (15)
John, Esther M (16) (17)
Guénel, Pascal (39) (40)
Truong, Thérèse (39) (40)
Sanchez, Marie (39) (40)
Burwinkel, Barbara (10) (41)
Marme, Frederik (41) (42)
Surowy, Harald (10) (41)
Wu, Anna H (23)
Benitez, Javier (43) (44)
Lu, Wei (48)
Cai, Hui (47)
Andrulis, Irene L (51) (52)
Knight, Julia A (51) (53)
Tomlinson, Ian (56) (57)
Teo, Soo Hwang (59) (60)
Blot, William (47) (62)
Shen, Chen-Yang (63) (64)
Wu, Pei-Ei (64)
Kristensen, Vessela N (66) (67) (68)
Giles, Graham G (22) (69)
Milne, Roger L (22) (69)
Trichopoulos, Dimitrios (3) (71) (72)
Peeters, Petra (33) (73)
Dossus, Laure (40) (78)
Schmutzler, Rita K (81) (82)
Yang, Rongxi (10) (41)
Muir, Kenneth (84) (85)
Hartman, Mikael (87) (88)
Miao, Hui (87) (88)
Chia, Kee Seng (87) (88)
Fasching, Peter A (89) (90)
Orr, Nick (8)
Zheng, Wei (47)
Goldberg, Mark S (92) (93)
Dumont, Martine (95) (96)
Brauch, Hiltrud (10) (100) (101)
Bernard, Loris (105) (106)
Dörk, Thilo (107)
Mannermaa, Arto (108) (109)
Kataja, Vesa (108) (110)
Kosma, Veli-Matti (108) (109)
Hartikainen, Jaana M (108) (109)
McKay, James (114)
Torres, Diana (10) (118)
Simard, Jacques (95) (96)
Hall, Per (5)

* Corresponding author

Affiliations

Organisations

  1. (1) University of Cambridge, grid.5335.0
  2. (2) QIMR Berghofer Medical Research Institute, grid.1049.c
  3. (3) Harvard University, grid.38142.3c
  4. (4) Antoni van Leeuwenhoek Hospital, grid.430814.a
  5. (5) Karolinska Institute, grid.4714.6
  6. (6) University of Copenhagen, grid.5254.6, KU
  7. (7) Herlev Hospital, grid.411900.d, Capital Region
  8. (8) Institute of Cancer Research, grid.18886.3f
  9. (9) London School of Hygiene & Tropical Medicine, grid.8991.9
  10. (10) German Cancer Research Center, grid.7497.d
  11. (11) University Medical Center Hamburg-Eppendorf, grid.13648.38
  12. (12) Helsinki University Central Hospital, grid.15485.3d
  13. (13) Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA
  14. (14) Center for Cancer Epidemiology and Prevention, University of Chicago, Chicago, Illinois, USA
  15. (15) University of Chicago, grid.170205.1
  16. (16) Stanford University, grid.168010.e
  17. (17) Cancer Prevention Institute of California, grid.280669.3
  18. (18) Fred Hutchinson Cancer Research Center, grid.270240.3
  19. (19) University of North Carolina at Chapel Hill, grid.10698.36
  20. (20) Columbia University, grid.21729.3f
  21. (21) Cancer Registry of Norway, grid.418941.1
  22. (22) University of Melbourne, grid.1008.9
  23. (23) University of Southern California, grid.42505.36
  24. (24) American Cancer Society, grid.422418.9
  25. (25) University of Hawaii at Manoa, grid.410445.0
  26. (26) Johns Hopkins Medicine, grid.469474.c
  27. (27) National Cancer Institute, grid.48336.3a
  28. (28) Flanders Institute for Biotechnology, grid.11486.3a
  29. (29) KU Leuven, grid.5596.f
  30. (30) Universitair Ziekenhuis Leuven, grid.410569.f
  31. (31) Mayo Clinic, grid.66875.3a
  32. (32) VU University Medical Center, grid.16872.3a
  33. (33) University Medical Center Utrecht, grid.7692.a
  34. (34) Genome Institute of Singapore, grid.418377.e
  35. (35) Seoul National University, grid.31501.36
  36. (36) Kyushu University, grid.177174.3
  37. (37) Aichi Cancer Center, grid.410800.d
  38. (38) Mie University Hospital, grid.412075.5
  39. (39) French Institute of Health and Medical Research, grid.7429.8
  40. (40) University of Paris-Sud, grid.5842.b
  41. (41) Heidelberg University, grid.7700.0
  42. (42) National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
  43. (43) Spanish National Cancer Research Centre, grid.7719.8
  44. (44) Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain
  45. (45) Hospital Universitario La Paz, grid.81821.32
  46. (46) Hospital Monte Naranco, grid.414858.4
  47. (47) Vanderbilt University, grid.152326.1
  48. (48) Shanghai Center for Disease Control and Prevention, Changning, China
  49. (49) Shanghai Cancer Institute, grid.419087.3
  50. (50) University of Sheffield, grid.11835.3e
  51. (51) University of Toronto, grid.17063.33
  52. (52) Lunenfeld-Tanenbaum Research Institute, grid.250674.2
  53. (53) Mount Sinai Hospital, grid.416166.2
  54. (54) University Health Network, grid.231844.8
  55. (55) King's College London, grid.13097.3c
  56. (56) University of Oxford, grid.4991.5
  57. (57) Wellcome Centre for Human Genetics, grid.270683.8
  58. (58) National University of Ireland, Galway, grid.6142.1
  59. (59) Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia
  60. (60) University Malaya Medical Centre, grid.413018.f
  61. (61) Erasmus University Medical Center, grid.5645.2
  62. (62) International Epidemiology Institute, grid.419344.f
  63. (63) China Medical University, grid.254145.3
  64. (64) Institute of Biomedical Sciences, Academia Sinica, grid.482251.8
  65. (65) Kaohsiung Medical University Chung-Ho Memorial Hospital, grid.412027.2
  66. (66) Department of Clinical Molecular Biology (EpiGen), University of Oslo, Oslo, Norway
  67. (67) University of Oslo, grid.5510.1
  68. (68) Oslo University Hospital, grid.55325.34
  69. (69) Cancer Council Victoria, grid.3263.4
  70. (70) The Alfred Hospital, grid.1623.6
  71. (71) Academy of Athens, grid.417593.d
  72. (72) Hellenic Health Foundation, grid.424637.0
  73. (73) Imperial College London, grid.7445.2
  74. (74) The Arctic University of Norway, grid.10919.30
  75. (75) Umeå University, grid.12650.30
  76. (76) Istituto per lo Studio e la Prevenzione Oncologica, grid.417623.5
  77. (77) Aarhus University, grid.7048.b, AU
  78. (78) INSERM Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, Villejuif, France
  79. (79) Department of Epidemiology, Consejería de Sanidad y Política Social, CIBER de Epidemiología y Salud Pública, Murcia, Spain
  80. (80) Technical University of Munich, grid.6936.a
  81. (81) University Hospital Cologne, grid.411097.a
  82. (82) University of Cologne, grid.6190.e
  83. (83) University Hospital Heidelberg, grid.5253.1
  84. (84) University of Manchester, grid.5379.8
  85. (85) University of Warwick, grid.7372.1
  86. (86) Ministry of Public Health, grid.415836.d
  87. (87) National University of Singapore, grid.4280.e
  88. (88) National University Health System, grid.410759.e
  89. (89) University of California, Los Angeles, grid.19006.3e
  90. (90) Department of Gynecology and Obstetrics, University Breast Center Franconia, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center of the Erlangen-Nuremberg Metropolitan Region, Erlangen, Germany
  91. (91) Krebsregister Saarland, grid.482902.5
  92. (92) McGill University, grid.14709.3b
  93. (93) Royal Victoria Hospital, grid.416229.a
  94. (94) University of Montreal, grid.14848.31
  95. (95) Centre Hospitalier Universitaire de Québec, grid.411081.d
  96. (96) Laval University, grid.23856.3a
  97. (97) University of Oulu, grid.10858.34
  98. (98) Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland
  99. (99) Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
  100. (100) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  101. (101) University of Tübingen, grid.10392.39
  102. (102) Ruhr University Bochum, grid.5570.7
  103. (103) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  104. (104) Fondazione Istituto FIRC (Italian Foundation for Cancer Research) di Oncologia Molecolare (IFOM), Milan, Italy
  105. (105) Cogentech Cancer Genetic Test Laboratory, Milan, Italy
  106. (106) European Institute of Oncology, grid.15667.33
  107. (107) Hannover Medical School, grid.10423.34
  108. (108) Kuopio University Hospital, grid.410705.7
  109. (109) University of Eastern Finland, grid.9668.1
  110. (110) Central Finland Health Care District, grid.460356.2
  111. (111) Leiden University Medical Center, grid.10419.3d
  112. (112) Pomeranian Medical University, grid.107950.a
  113. (113) National Cancer Institute of Thailand, grid.419173.9
  114. (114) International Agency For Research On Cancer, grid.17703.32
  115. (115) The Ohio State University, grid.261331.4
  116. (116) Roswell Park Cancer Institute, grid.240614.5
  117. (117) National Centre of Scientific Research Demokritos, grid.6083.d
  118. (118) Pontificia Universidad Javeriana, grid.41312.35
  119. (119) City Of Hope National Medical Center, grid.410425.6
  120. (120) University of California, Irvine, grid.266093.8
  121. (121) McGill University and Génome Québec Innovation Centre, grid.411640.6

Description

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

Funders

Research Categories

Main Subject Area

Links & Metrics

NORA University Profiles

University of Copenhagen

Aarhus University

Danish Open Access Indicator

2015: Unused

Research area: Medicine

Danish Bibliometrics Indicator

2015: Level 2

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 336

Field Citation Ratio (FCR): 57.74

Relative Citation ratio (RCR): 13.39

Open Access Info

Green, Published