Article open access publication

RAD51B in Familial Breast Cancer

PLoS ONE, Public Library of Science (PLoS), ISSN 1932-6203

Volume 11, 5, 2016

DOI:10.1371/journal.pone.0153788, Dimensions: pub.1053490740, PMC: PMC4858276, PMID: 27149063,

Authors

Schleutker, Johanna (3) (4) (5)
Wang, Qin (10)
Fasching, Peter A. (14) (15)
Burwinkel, Barbara (19) (20)
Surowy, Harald (19) (20)
Guénel, Pascal (21) (22)
Truong, Thérèse (21) (22)
Bojesen, Stig E. (23) (24)
Benitez, Javier (25) (26)
Brauch, Hiltrud (20) (32) (33)
Mannermaa, Arto (36) (37)
Van Dyck, Laurien (39) (40)
Giles, Graham G (13) (46)
Milne, Roger L. (13) (46)
Kristensen, Vessela (49) (50) (51)
Zheng, Wei (52)
Andrulis, Irene L. (54) (55)
Torres, Diana (20) (59)
Orr, Nick (12)
Hall, Per (35)

* Corresponding author

Affiliations

Organisations

  1. (1) Helsinki University Central Hospital, grid.15485.3d
  2. (2) University of Oulu, grid.10858.34
  3. (3) Turku University Hospital, grid.410552.7
  4. (4) University of Turku, grid.1374.1
  5. (5) Tampere University, grid.502801.e
  6. (6) Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland
  7. (7) Fimlab Laboratories, Tampere, Finland
  8. (8) Hannover Medical School, grid.10423.34
  9. (9) National Cancer Institute, grid.48336.3a
  10. (10) University of Cambridge, grid.5335.0
  11. (11) Antoni van Leeuwenhoek Hospital, grid.430814.a
  12. (12) Institute of Cancer Research, grid.18886.3f
  13. (13) University of Melbourne, grid.1008.9
  14. (14) University of California, Los Angeles, grid.19006.3e
  15. (15) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  16. (16) London School of Hygiene & Tropical Medicine, grid.8991.9
  17. (17) King's College London, grid.13097.3c
  18. (18) University of Oxford, grid.4991.5
  19. (19) Heidelberg University, grid.7700.0
  20. (20) German Cancer Research Center, grid.7497.d
  21. (21) French Institute of Health and Medical Research, grid.7429.8
  22. (22) University of Paris-Sud, grid.5842.b
  23. (23) Herlev Hospital, grid.411900.d, Capital Region
  24. (24) University of Copenhagen, grid.5254.6, KU
  25. (25) Centro de Investigación en Red de Enfermedades Raras, Valencia, Spain
  26. (26) Spanish National Cancer Research Centre, grid.7719.8
  27. (27) City Of Hope National Medical Center, grid.410425.6
  28. (28) University of California, Irvine, grid.266093.8
  29. (29) Technical University of Munich, grid.6936.a
  30. (30) University Hospital Cologne, grid.411097.a
  31. (31) University of Cologne, grid.6190.e
  32. (32) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  33. (33) University of Tübingen, grid.10392.39
  34. (34) Ruhr University Bochum, grid.5570.7
  35. (35) Karolinska Institute, grid.4714.6
  36. (36) Kuopio University Hospital, grid.410705.7
  37. (37) University of Eastern Finland, grid.9668.1
  38. (38) QIMR Berghofer Medical Research Institute, grid.1049.c
  39. (39) Flanders Institute for Biotechnology, grid.11486.3a
  40. (40) KU Leuven, grid.5596.f
  41. (41) Universitair Ziekenhuis Leuven, grid.410569.f
  42. (42) University Cancer Center Hamburg, grid.412315.0
  43. (43) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  44. (44) IFOM, Fondazione Istituto FIRC (Italian Foundation of Cancer Research) di Oncologia Molecolare, Milan, Italy
  45. (45) Mayo Clinic, grid.66875.3a
  46. (46) Cancer Council Victoria, grid.3263.4
  47. (47) University of Southern California, grid.42505.36
  48. (48) Laval University, grid.23856.3a
  49. (49) Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
  50. (50) K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  51. (51) Oslo University Hospital, grid.55325.34
  52. (52) Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
  53. (53) Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
  54. (54) University of Toronto, grid.17063.33
  55. (55) Lunenfeld-Tanenbaum Research Institute, grid.250674.2
  56. (56) Leiden University Medical Center, grid.10419.3d
  57. (57) Erasmus University Medical Center, grid.5645.2
  58. (58) University of Sheffield, grid.11835.3e
  59. (59) Pontificia Universidad Javeriana, grid.41312.35
  60. (60) Pomeranian Medical University, grid.107950.a
  61. (61) National Centre of Scientific Research Demokritos, grid.6083.d

Description

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

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Times Cited: 15

Field Citation Ratio (FCR): 3.88

Relative Citation ratio (RCR): 0.63

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