Article open access publication

Common germline polymorphisms associated with breast cancer-specific survival

Breast Cancer Research, Springer Nature, ISSN 1465-5411

Volume 17, 1, 2015

DOI:10.1186/s13058-015-0570-7, Dimensions: pub.1044034748, PMC: PMC4484708, PMID: 25897948,

Authors

Guo, Qi (1)
Wang, Qin (1)
Knight, Julia A (17) (18)
Giles, Graham G (23) (25)
Milne, Roger L (23) (25)
Marme, Federick (31) (32)
Burwinkel, Barbara (13) (32)
Chanock, Stephen J (33) (34)
Kosma, Veli-Matti (40) (41)
Benitez, Javier (50) (51)
Nord, Siljie (57) (58)
Abraham, Jean (1) (60)
Earl, Helena (1) (60)
Yang, Rose (33)
Campa, Daniele (13) (63)
Hankinson, Susan (2) (65) (66)
Caldas, Carlos (1) (60) (67)
Mannermaa, Arto (40) (41)
Andrulis, Irene L (18) (19)
Hall, Per (7)
Bojesen, Stig E (11) (12)
Fasching, Peter A (47) (69)

* Corresponding author

Affiliations

Organisations

  1. (1) University of Cambridge, grid.5335.0
  2. (2) Harvard University, grid.38142.3c
  3. (3) Antoni van Leeuwenhoek Hospital, grid.430814.a
  4. (4) University of Southampton, grid.5491.9
  5. (5) Institute of Cancer Research, grid.18886.3f
  6. (6) Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 8, FIN-00029 HUS, Helsinki, Finland
  7. (7) Karolinska Institute, grid.4714.6
  8. (8) Flanders Institute for Biotechnology, grid.11486.3a
  9. (9) KU Leuven, grid.5596.f
  10. (10) Universitair Ziekenhuis Leuven, grid.410569.f
  11. (11) University of Copenhagen, grid.5254.6, KU
  12. (12) Herlev Hospital, grid.411900.d, Capital Region
  13. (13) German Cancer Research Center, grid.7497.d
  14. (14) University Medical Center Hamburg-Eppendorf, grid.13648.38
  15. (15) Helsinki University Central Hospital, grid.15485.3d
  16. (16) Mayo Clinic, grid.66875.3a
  17. (17) Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Toronto, ON, Canada
  18. (18) University of Toronto, grid.17063.33
  19. (19) Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Toronto, ON, Canada
  20. (20) University Health Network, grid.231844.8
  21. (21) University of Southern California, grid.42505.36
  22. (22) University of Hawaii at Manoa, grid.410445.0
  23. (23) University of Melbourne, grid.1008.9
  24. (24) University of Sheffield, grid.11835.3e
  25. (25) Cancer Council Victoria, grid.3263.4
  26. (26) The Alfred Hospital, grid.1623.6
  27. (27) Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital, Kajaanintie 50, FI-90220, Oulu, Finland
  28. (28) Department of Oncology, Oulu University Hospital, University of Oulu, Kajaanintie 50, FI-90220, Oulu, Finland
  29. (29) Department of Surgery, Oulu University Hospital, University of Oulu, Kajaanintie 50, FI-90220, Oulu, Finland
  30. (30) Department of Medical Oncology, Family Cancer Clinic, Erasmus McCancer Institute, ’s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands
  31. (31) National Center for Tumor Diseases, University of Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany
  32. (32) Heidelberg University, grid.7700.0
  33. (33) National Cancer Institute, grid.48336.3a
  34. (34) Frederick National Laboratory for Cancer Research, grid.418021.e
  35. (35) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  36. (36) King's College London, grid.13097.3c
  37. (37) University of Oxford, grid.4991.5
  38. (38) University Hospital Galway, grid.412440.7
  39. (39) Krebsregister Saarland, grid.482902.5
  40. (40) Kuopio University Hospital, grid.410705.7
  41. (41) University of Eastern Finland, grid.9668.1
  42. (42) Leiden University Medical Center, grid.10419.3d
  43. (43) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  44. (44) FIRC Institute of Molecular Oncology, grid.7678.e
  45. (45) Cogentech Cancer Genetic Test Laboratory, Via Adamello 16, 20139, Milan, Italy
  46. (46) Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Emn, Universitaetsstrasse 21-23, 91054, Erlangen, Germany
  47. (47) Institute of Human Genetics; University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Emn, Universitaetsstrasse 21-23, 91054, Erlangen, Germany
  48. (48) University of Sydney, grid.1013.3
  49. (49) Peter MacCallum Cancer Centre, grid.1055.1
  50. (50) Centro de Investigación En Red De Enfermedades Raras (CIBERER), Calle de Álvaro de Bazán, 10 Bajo, 46010, Valencia, Spain
  51. (51) Spanish National Cancer Research Centre, grid.7719.8
  52. (52) Hospital Universitario La Paz, grid.81821.32
  53. (53) Hospital Monte Naranco, grid.414858.4
  54. (54) Pomeranian Medical University, grid.107950.a
  55. (55) Frauenklinik der Stadtklinik Baden-Baden, Balger Strasse 50, 76532, Baden-Baden, Germany
  56. (56) Charité, grid.6363.0
  57. (57) Oslo University Hospital, grid.55325.34
  58. (58) University of Oslo, grid.5510.1
  59. (59) University of Manchester, grid.5379.8
  60. (60) Cambridge Experimental Cancer Medicine Centre, Robinson Way, CB2 0RE, Cambridge, UK
  61. (61) University of Warwick, grid.7372.1
  62. (62) Cancer Research UK Clinical Trials Unit, grid.470294.c
  63. (63) University of Pisa, grid.5395.a
  64. (64) American Cancer Society, grid.422418.9
  65. (65) Brigham and Women's Hospital, grid.62560.37
  66. (66) University of Massachusetts Amherst, grid.266683.f
  67. (67) Cancer Research UK Cambridge Institute, grid.470869.4
  68. (68) QIMR Berghofer Medical Research Institute, grid.1049.c
  69. (69) University of California, Los Angeles, grid.19006.3e

Description

INTRODUCTION: Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. METHODS: A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. RESULTS: Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease. CONCLUSIONS: Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels.

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Times Cited: 18

Field Citation Ratio (FCR): 3.97

Relative Citation ratio (RCR): 0.6

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