Article open access publication

Fine‐scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer

International Journal of Cancer, Wiley, ISSN 0020-7136

Volume 139, 6, 2016

DOI:10.1002/ijc.30150, Dimensions: pub.1019953469, PMC: PMC5110427, PMID: 27087578,

Authors

Wang, Qin (2)
Milne, Roger L. (3) (4)
Benitez, Javier (11) (12)
Blot, William (1) (13)
Bojesen, Stig E. (15) (16) (17)
Brauch, Hiltrud (9) (18) (19)
Cai, Hui (1)
Fasching, Peter A. (10) (30)
Giles, Graham G (3) (4)
Guenel, Pascal (37) (38)
Hartman, Mikael (41) (42)
Miao, Hui (41)
Torres, Diana (40) (48)
Kosma, Veli-Matti (50) (51)
Mannermaa, Arto (50) (51)
Marme, Frederik (57) (58)
Muir, Kenneth (54) (61)
Nord, Silje (63) (64)
Orr, Nick (35)
Shen, Chen-Yang (71) (72)
Teo, Soo Hwang (74) (75)
Thienpont, Bernard (52) (53)
Truong, Therese (37) (38)
Winqvist, Robert (78) (79)
Wu, Anna H (39)
Kristensen, Vessela N. (63) (64) (83)
Hall, Per (27)

Affiliations

Organisations

  1. (1) Vanderbilt Epidemiology Center, Vanderbilt‐Ingram Cancer Center, Vanderbilt University School of Medicine Division of Epidemiology Department of Medicine Nashville TN
  2. (2) University of Cambridge, grid.5335.0
  3. (3) Cancer Council Victoria, grid.3263.4
  4. (4) University of Melbourne, grid.1008.9
  5. (5) QIMR Berghofer Medical Research Institute, grid.1049.c
  6. (6) Lunenfeld-Tanenbaum Research Institute, grid.250674.2
  7. (7) University of Toronto, grid.17063.33
  8. (8) University of California, Irvine, grid.266093.8
  9. (9) German Cancer Research Center, grid.7497.d
  10. (10) University Hospital Erlangen, Friedrich‐Alexander University Erlangen‐Nuremberg Department of Gynaecology and Obstetrics Erlangen Germany
  11. (11) Centro De Investigación En Red De Enfermedades Raras Valencia Spain
  12. (12) Spanish National Cancer Research Centre, grid.7719.8
  13. (13) International Epidemiology Institute Rockville MD
  14. (14) Hannover Medical School, grid.10423.34
  15. (15) Herlev Hospital, grid.411900.d, Capital Region
  16. (16) Herlev Hospital, Copenhagen University Hospital Department of Clinical Biochemistry Herlev Denmark
  17. (17) University of Copenhagen, grid.5254.6, KU
  18. (18) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  19. (19) University of Tübingen, grid.10392.39
  20. (20) National Cancer Institute Division of Cancer Epidemiology and Genetics Rockville MD
  21. (21) Antoni Van Leeuwenhoek Hospital, Netherlands Cancer Institute Amsterdam The Netherlands
  22. (22) Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Bochum Germany
  23. (23) Netherlands Cancer Institute Antoni Van Leeuwenhoek Hospital Amsterdam The Netherlands
  24. (24) Seoul National University, grid.31501.36
  25. (25) Mayo Clinic Department of Laboratory Medicine and Pathology Rochester MN
  26. (26) University of Sheffield, grid.11835.3e
  27. (27) Karolinska Institute, grid.4714.6
  28. (28) Leiden University Medical Center, grid.10419.3d
  29. (29) Centre Hospitalier Universitaire De Québec Research Center, Laval University Québec City Canada
  30. (30) University of California, Los Angeles, grid.19006.3e
  31. (31) Breakthrough Breast Cancer Research Centre, Institute of Cancer Research Division of Cancer Studies London United Kingdom
  32. (32) Herlev Hospital, Copenhagen University Hospital Department of Breast Surgery Herlev Denmark
  33. (33) IRRP, National Centre for Scientific Research “Demokritos,” Molecular Diagnostics Laboratory Athens Greece
  34. (34) International Agency For Research On Cancer, grid.17703.32
  35. (35) Institute of Cancer Research, grid.18886.3f
  36. (36) Oulu University Hospital, grid.412326.0
  37. (37) Center for Research in Epidemiology and Population Health, INSERM Environmental Epidemiology of Cancer Villejuif France
  38. (38) University of Paris-Sud, grid.5842.b
  39. (39) University of Southern California Department of Preventive Medicine, Keck School of Medicine Los Angeles CA
  40. (40) Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ) Heidelberg Germany
  41. (41) National University of Singapore, grid.4280.e
  42. (42) National University Health System, grid.410759.e
  43. (43) Erasmus University Medical Center, grid.5645.2
  44. (44) Technical University of Munich, grid.6936.a
  45. (45) Institute of Biomedical Sciences, Academia Sinica Taipei Taiwan
  46. (46) Aichi Cancer Center, grid.410800.d
  47. (47) Pomeranian Medical University, grid.107950.a
  48. (48) Pontificia Universidad Javeriana, grid.41312.35
  49. (49) Helsinki University Central Hospital, University of Helsinki Department of Obstetrics and Gynecology Helsinki Finland
  50. (50) Institute of Clinical Medicine, Pathology and Forensic Medicine and Cancer Center of Eastern Finland, University of Eastern Finland School of Medicine Kuopio Finland
  51. (51) Kuopio University Hospital Imaging Center, Department of Clinical Pathology Kuopio Finland
  52. (52) KU Leuven, grid.5596.f
  53. (53) Vesalius Research Center Leuven Belgium
  54. (54) University of Warwick, grid.7372.1
  55. (55) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  56. (56) University of Hawaii Cancer Center Honolulu HI
  57. (57) Heidelberg University, grid.7700.0
  58. (58) National Center for Tumor Diseases, University of Heidelberg Heidelberg Germany
  59. (59) Kyushu University, grid.177174.3
  60. (60) The Alfred Hospital, grid.1623.6
  61. (61) Institute of Population Health, University of Manchester Manchester United Kingdom
  62. (62) Beckman Research Institute of City of Hope Duarte CA
  63. (63) Institute for Cancer Research, Oslo University Hospital Department of Genetics Oslo Norway
  64. (64) Institute for Clinical Medicine, Faculty of Medicine, University of Oslo K.G. Jebsen Center for Breast Cancer Research Oslo Norway
  65. (65) Mayo Clinic Department of Health Sciences Research Rochester MN
  66. (66) IFOM, The FIRC Institute of Molecular Oncology Milan Italy
  67. (67) National Cancer Institute of Thailand, grid.419173.9
  68. (68) Research Oncology, Guy's Hospital, King's College London London United Kingdom
  69. (69) University Hospital Cologne, grid.411097.a
  70. (70) University Hospital of Cologne Division of Molecular Gyneco‐Oncology, Department of Gynaecology and Obstetrics Cologne Germany
  71. (71) China Medical University, grid.254145.3
  72. (72) Institute of Biomedical Sciences, Academia Sinica, grid.482251.8
  73. (73) Chung‐Ho Memorial Hospital, Kaohsiung Medical University Cancer Center and Department of Surgery Kaohsiung Taiwan
  74. (74) Cancer Research Initiatives Foundation Subang Jaya Selangor Malaysia
  75. (75) Cancer Research Institute, University Malaya Medical Centre Breast Cancer Research Unit Kuala Lumpur Malaysia
  76. (76) Comprehensive Cancer Center, The Ohio State University Department of Molecular Virology, Immunology and Medical Genetics Columbus OH
  77. (77) University of Oxford, grid.4991.5
  78. (78) Northern Finland Laboratory Centre NordLab Laboratory of Cancer Genetics and Tumor Biology Oulu Finland
  79. (79) University of Oulu, grid.10858.34
  80. (80) Hospital Universitario La Paz, grid.81821.32
  81. (81) Shanghai Municipal Center For Disease Control Prevention, grid.430328.e
  82. (82) Universitair Ziekenhuis Leuven, grid.410569.f
  83. (83) Akershus University Hospital, University of Oslo (UiO) Department of Clinical Molecular Biology (EpiGen) Oslo Norway

Description

Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.

Funders

Research Categories

Main Subject Area

Fields of Research

Links & Metrics

NORA University Profiles

University of Copenhagen

Danish Open Access Indicator

2016: Unused

Research area: Medicine

Danish Bibliometrics Indicator

2016: Level 1

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 17

Field Citation Ratio (FCR): 4.43

Relative Citation ratio (RCR): 0.92

Open Access Info

Bronze