Article open access publication

Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry

Cancer Causes & Control, Springer Nature, ISSN 1573-7225

Volume 27, 5, 2016

DOI:10.1007/s10552-016-0741-6, Dimensions: pub.1002734250, PMC: PMC5029371, PMID: 27053251,

Authors

Zhao, Zhiguo (1) (2)
Wang, Qin (3)
Milne, Roger L. (5) (6)
Bojesen, Stig E. (11) (12)
Andrulis, Irene L. (15) (16)
Benitez, Javier (19) (20)
Brauch, Hiltrud (9) (26) (27)
Fasching, Peter A. (18) (33)
Giles, Graham G (5) (6)
Guénel, Pascal (38) (39)
John, Esther M (43) (44)
Knight, Julia A. (15) (16)
Kosma, Veli-Matti (46) (47)
Kristensen, Vessela (23) (24) (48)
Mannermaa, Arto (46) (47)
Marme, Frederik (53) (54)
Miao, Hui (40)
Muir, Kenneth (50) (58)
Phillips, Kelly-Anne (6) (62) (63)
Santella, Regina (65) (66)
Truong, Thérèse (38) (39)
Ursin, Giske (71) (72)
Winqvist, Robert (64) (74)
Zhao, Hui (76) (77)
Hall, Per (25)
Zheng, Wei * (2)

* Corresponding author

Affiliations

Organisations

  1. (1) Vanderbilt University, grid.152326.1
  2. (2) Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, 37203-1738, Nashville, TN, USA
  3. (3) University of Cambridge, grid.5335.0
  4. (4) Antoni van Leeuwenhoek Hospital, grid.430814.a
  5. (5) Cancer Council Victoria, grid.3263.4
  6. (6) University of Melbourne, grid.1008.9
  7. (7) Institute of Cancer Research, grid.18886.3f
  8. (8) University of Ulm, grid.6582.9
  9. (9) German Cancer Research Center, grid.7497.d
  10. (10) Harvard University, grid.38142.3c
  11. (11) University of Copenhagen, grid.5254.6, KU
  12. (12) Herlev Hospital, grid.411900.d, Capital Region
  13. (13) University of Chicago, grid.170205.1
  14. (14) Department of Clinical Genetics, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
  15. (15) Mount Sinai Hospital, grid.416166.2
  16. (16) University of Toronto, grid.17063.33
  17. (17) University of California, Irvine, grid.266093.8
  18. (18) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany
  19. (19) Centro de Investigación en Red de Enfermedades Raras, Valencia, Spain
  20. (20) Spanish National Cancer Research Centre, grid.7719.8
  21. (21) Department of Oncology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
  22. (22) Hannover Medical School, grid.10423.34
  23. (23) K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  24. (24) Oslo University Hospital, grid.55325.34
  25. (25) Karolinska Institute, grid.4714.6
  26. (26) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  27. (27) University of Tübingen, grid.10392.39
  28. (28) University of Southern California, grid.42505.36
  29. (29) QIMR Berghofer Medical Research Institute, grid.1049.c
  30. (30) Mayo Clinic, grid.66875.3a
  31. (31) University of Sheffield, grid.11835.3e
  32. (32) Laval University, grid.23856.3a
  33. (33) University of California, Los Angeles, grid.19006.3e
  34. (34) National Cancer Institute, grid.48336.3a
  35. (35) University Medical Center Hamburg-Eppendorf, grid.13648.38
  36. (36) National Centre of Scientific Research Demokritos, grid.6083.d
  37. (37) University of North Carolina at Chapel Hill, grid.10698.36
  38. (38) French Institute of Health and Medical Research, grid.7429.8
  39. (39) University of Paris-Sud, grid.5842.b
  40. (40) National University of Singapore, grid.4280.e
  41. (41) Erasmus University Medical Center, grid.5645.2
  42. (42) Pomeranian Medical University, grid.107950.a
  43. (43) Cancer Prevention Institute of California, grid.280669.3
  44. (44) Stanford University, grid.168010.e
  45. (45) Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
  46. (46) Kuopio University Hospital, grid.410705.7
  47. (47) University of Eastern Finland, grid.9668.1
  48. (48) Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
  49. (49) University of Hawaii at Manoa, grid.410445.0
  50. (50) University of Warwick, grid.7372.1
  51. (51) Fred Hutchinson Cancer Research Center, grid.270240.3
  52. (52) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  53. (53) Heidelberg University, grid.7700.0
  54. (54) National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
  55. (55) The Alfred Hospital, grid.1623.6
  56. (56) VU University Medical Center, grid.16872.3a
  57. (57) Technical University of Munich, grid.6936.a
  58. (58) University of Manchester, grid.5379.8
  59. (59) City Of Hope National Medical Center, grid.410425.6
  60. (60) Universitair Ziekenhuis Leuven, grid.410569.f
  61. (61) FIRC Institute of Molecular Oncology, grid.7678.e
  62. (62) Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Australia
  63. (63) Peter MacCallum Cancer Center, The University of Melbourne, Melbourne, Australia
  64. (64) University of Oulu, grid.10858.34
  65. (65) Columbia University, grid.21729.3f
  66. (66) Columbia University Medical Center, grid.239585.0
  67. (67) King's College London, grid.13097.3c
  68. (68) University Hospital Cologne, grid.411097.a
  69. (69) The Ohio State University, grid.261331.4
  70. (70) University of Oxford, grid.4991.5
  71. (71) Cancer Registry of Norway, grid.418941.1
  72. (72) University of Oslo, grid.5510.1
  73. (73) University Medical Center Utrecht, grid.7692.a
  74. (74) Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland
  75. (75) Hospital Universitario La Paz, grid.81821.32
  76. (76) KU Leuven, grid.5596.f
  77. (77) Vesalius Research Center, Louvain, Belgium

Description

PURPOSE: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. METHODS: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. RESULTS: The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92-0.95, p = 4.13E-13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02-1.06, p = 1.26E-05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95-0.99, p = 8.05E-04). CONCLUSIONS: We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.

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University of Copenhagen

Danish Open Access Indicator

2016: Unused

Research area: Medicine

Danish Bibliometrics Indicator

2016: Level 2

Research area: Medicine

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Times Cited: 12

Field Citation Ratio (FCR): 3.51

Relative Citation ratio (RCR): 0.65

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Green, Accepted