Article open access publication

rs2735383, located at a microRNA binding site in the 3’UTR of NBS1, is not associated with breast cancer risk

Scientific Reports, Springer Nature, ISSN 2045-2322

Volume 6, 1, 2016

DOI:10.1038/srep36874, Dimensions: pub.1030130880, PMC: PMC5109293, PMID: 27845421,

Authors

Wang, Qin (2)
Behrens, Sabine (8) (9)
Benitez, Javier (10) (11)
Boeckx, Bram (13) (14)
Bojesen, Stig E. (17) (18) (19)
Brauch, Hiltrud (8) (20) (21)
Cheng, Ching Y. (27) (28) (29) (30)
Figueroa, Jonine (37) (38)
Giles, Graham G (40) (41)
Hartman, Mikael (29) (30)
Ito, Hidemi (46) (47)
Kosma, Veli-Matti (49) (50)
Mannermaa, Arto (49) (50)
Matsuo, Keitaro (46) (47)
Milne, Roger L. (40) (41)
Kåresen, Rolf (52) (57)
Sauer, Toril (57) (58)
Engebråten, Olav (52) (57)
Bukholm, Ida (52) (58)
Orr, Nick (63)
Pylkäs, Katri (65) (66)
Shen, Chen-Yang (71) (72)
Teo, Soo H. (75) (76)
Torres, Diana (8) (79)
Winqvist, Robert (65) (66)
Wu, Anna H (44)
Zheng, Wei (73)
Hall, Per (34)

Affiliations

Organisations

  1. (1) Erasmus University Medical Center, grid.5645.2
  2. (2) University of Cambridge, grid.5335.0
  3. (3) Cyprus Institute of Neurology and Genetics, grid.417705.0
  4. (4) University of Toronto, grid.17063.33
  5. (5) Mount Sinai Hospital, grid.416166.2
  6. (6) European Institute of Oncology, grid.15667.33
  7. (7) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  8. (8) German Cancer Research Center, grid.7497.d
  9. (9) University Cancer Center Hamburg, grid.412315.0
  10. (10) Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain
  11. (11) Spanish National Cancer Research Centre, grid.7719.8
  12. (12) Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  13. (13) Flanders Institute for Biotechnology, grid.11486.3a
  14. (14) KU Leuven, grid.5596.f
  15. (15) N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus
  16. (16) Hannover Medical School, grid.10423.34
  17. (17) Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  18. (18) Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  19. (19) University of Copenhagen, grid.5254.6, KU
  20. (20) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  21. (21) University of Tübingen, grid.10392.39
  22. (22) International Agency For Research On Cancer, grid.17703.32
  23. (23) Antoni van Leeuwenhoek Hospital, grid.430814.a
  24. (24) Heidelberg University, grid.7700.0
  25. (25) Changhua Christian Hospital, grid.413814.b
  26. (26) QIMR Berghofer Medical Research Institute, grid.1049.c
  27. (27) Duke NUS Graduate Medical School, grid.428397.3
  28. (28) Singapore Eye Research Institute, grid.272555.2
  29. (29) National University Health System, grid.410759.e
  30. (30) National University of Singapore, grid.4280.e
  31. (31) Seoul National University, grid.31501.36
  32. (32) Mayo Clinic, grid.66875.3a
  33. (33) University of Sheffield, grid.11835.3e
  34. (34) Karolinska Institute, grid.4714.6
  35. (35) London School of Hygiene & Tropical Medicine, grid.8991.9
  36. (36) University of California, Los Angeles, grid.19006.3e
  37. (37) University of Edinburgh, grid.4305.2
  38. (38) National Cancer Institute, grid.48336.3a
  39. (39) Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  40. (40) University of Melbourne, grid.1008.9
  41. (41) Cancer Council Victoria, grid.3263.4
  42. (42) McGill University, grid.14709.3b
  43. (43) Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France
  44. (44) University of Southern California, grid.42505.36
  45. (45) Universitair Ziekenhuis Leuven, grid.410569.f
  46. (46) Aichi Cancer Center, grid.410800.d
  47. (47) Nagoya University, grid.27476.30
  48. (48) Pomeranian Medical University, grid.107950.a
  49. (49) Kuopio University Hospital, grid.410705.7
  50. (50) University of Eastern Finland, grid.9668.1
  51. (51) Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
  52. (52) Oslo University Hospital, grid.55325.34
  53. (53) University of Hawaii at Manoa, grid.410445.0
  54. (54) University of Manchester, grid.5379.8
  55. (55) University of Warwick, grid.7372.1
  56. (56) Department of Research, Vestre Viken, Drammen, Norway
  57. (57) University of Oslo, grid.5510.1
  58. (58) Akershus University Hospital, grid.411279.8
  59. (59) Haukeland University Hospital, grid.412008.f
  60. (60) University of Bergen, grid.7914.b
  61. (61) City Of Hope National Medical Center, grid.410425.6
  62. (62) Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  63. (63) Institute of Cancer Research, grid.18886.3f
  64. (64) Hospital Monte Naranco, grid.414858.4
  65. (65) Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland
  66. (66) University of Oulu, grid.10858.34
  67. (67) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  68. (68) National Cancer Institute of Thailand, grid.419173.9
  69. (69) King's College London, grid.13097.3c
  70. (70) National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
  71. (71) China Medical University, grid.254145.3
  72. (72) Institute of Biomedical Sciences, Academia Sinica, grid.482251.8
  73. (73) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
  74. (74) Laval University, grid.23856.3a
  75. (75) Cancer Research Malaysia, grid.507182.9
  76. (76) University Malaya Medical Centre, grid.413018.f
  77. (77) McGill University and Génome Québec Innovation Centre, grid.411640.6
  78. (78) University of Oxford, grid.4991.5
  79. (79) Pontificia Universidad Javeriana, grid.41312.35
  80. (80) National Centre of Scientific Research Demokritos, grid.6083.d
  81. (81) Cancer Genomics Netherlands, Utrecht, The Netherlands

Description

NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3'-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936-1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r2 > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969-1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905-1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.

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Relative Citation ratio (RCR): 0.08

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