Article open access publication

Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer

Carcinogenesis, Oxford University Press (OUP), ISSN 0143-3334

Volume 36, 2, 2015

DOI:10.1093/carcin/bgu326, Dimensions: pub.1002029030, PMC: PMC4335262, PMID: 25586992,

Authors

Wang, Qin (3)
Guénel, Pascal (23) (24)
Truong, Thérèse (23) (24)
Menegaux, Florence (23) (24)
Sanchez, Marie (23) (24)
Marmé, Frederik (25) (26)
Yang, Rongxi (1) (25)
Andrulis, Irene L. (31) (32)
Knight, Julia A. (31) (33)
Giles, Graham G (42) (46)
Milne, Roger L. (42) (46)
Ruebner, Matthias (48) (49)
Ekici, Arif B. (48) (50)
Swerdlow, Anthony (17) (52)
Goldberg, Mark S (55) (56)
Fortuzzi, Stefano (65) (66)
Zheng, Wei (73)
Torres, Diana (1) (74)
Hall, Per (5)

Affiliations

Organisations

  1. (1) German Cancer Research Center, grid.7497.d
  2. (2) University Hospital Heidelberg, grid.5253.1
  3. (3) Department of Public Health and Primary Care and
  4. (4) University of Cambridge, grid.5335.0
  5. (5) Karolinska Institute, grid.4714.6
  6. (6) Copenhagen General Population Study,
  7. (7) Department of Clinical Biochemistry, and
  8. (8) Herlev Hospital, grid.411900.d, Capital Region
  9. (9) Flanders Institute for Biotechnology, grid.11486.3a
  10. (10) KU Leuven, grid.5596.f
  11. (11) Department of Oncology, KU Leuven (University of Leuven), Multidisciplinary Breast Center, University Hospitals Leuven, 3000 Leuven, Belgium,
  12. (12) Department of Laboratory Medicine and Pathology and
  13. (13) Mayo Clinic, grid.66875.3a
  14. (14) Karmanos Cancer Institute, grid.477517.7
  15. (15) University Medical Center Hamburg-Eppendorf, grid.13648.38
  16. (16) London School of Hygiene & Tropical Medicine, grid.8991.9
  17. (17) Institute of Cancer Research, grid.18886.3f
  18. (18) Department of Obstetrics and Gynecology,
  19. (19) Department of Clinical Genetics and
  20. (20) Helsinki University Central Hospital, grid.15485.3d
  21. (21) Antoni van Leeuwenhoek Hospital, grid.430814.a
  22. (22) Genome Institute of Singapore, grid.418377.e
  23. (23) Délégation Paris 11, grid.457369.a
  24. (24) University of Paris-Sud, grid.5842.b
  25. (25) Heidelberg University, grid.7700.0
  26. (26) National Center for Tumor Diseases, University of Heidelberg, 69120 Heidelberg, Germany,
  27. (27) Human Genotyping-CEGEN Unit and
  28. (28) Hospital Universitario La Paz, grid.81821.32
  29. (29) Hospital Monte Naranco, grid.414858.4
  30. (30) University of Sheffield, grid.11835.3e
  31. (31) University of Toronto, grid.17063.33
  32. (32) Lunenfeld-Tanenbaum Research Institute, grid.250674.2
  33. (33) Mount Sinai Hospital, grid.416166.2
  34. (34) King's College London, grid.13097.3c
  35. (35) University of Oxford, grid.4991.5
  36. (36) University Hospital Galway, grid.412440.7
  37. (37) University of Southern California, grid.42505.36
  38. (38) University of Hawaii at Manoa, grid.410445.0
  39. (39) Department of Molecular Medicine and Surgery and
  40. (40) Department of Medical Oncology and
  41. (41) Erasmus University Medical Center, grid.5645.2
  42. (42) Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health and
  43. (43) University of Melbourne, grid.1008.9
  44. (44) The Ohio State University, grid.261331.4
  45. (45) National Centre of Scientific Research Demokritos, grid.6083.d
  46. (46) Cancer Council Victoria, grid.3263.4
  47. (47) The Alfred Hospital, grid.1623.6
  48. (48) Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany,
  49. (49) Department of Gynecology and Obstetrics, University Breast Center Franconia, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany,
  50. (50) Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany,
  51. (51) Krebsregister Saarland, grid.482902.5
  52. (52) Division of Genetics and Epidemiology and
  53. (53) National Cancer Institute, grid.48336.3a
  54. (54) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  55. (55) McGill University, grid.14709.3b
  56. (56) Royal Victoria Hospital, grid.416229.a
  57. (57) University of Montreal, grid.14848.31
  58. (58) Centre Hospitalier Universitaire de Québec, grid.411081.d
  59. (59) University of Oulu, grid.10858.34
  60. (60) Department of Oncology and
  61. (61) Department of Surgery, Oulu University Hospital, University of Oulu, FI-90220 Oulu, Finland,
  62. (62) Ruhr University Bochum, grid.5570.7
  63. (63) Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, 53113 Bonn, Germany,
  64. (64) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  65. (65) FIRC Institute of Molecular Oncology, grid.7678.e
  66. (66) Cogentech Cancer Genetic Test Laboratory, 20139 Milan, Italy,
  67. (67) Department of Radiation Oncology and
  68. (68) Hannover Medical School, grid.10423.34
  69. (69) Department of Human Genetics and Department of Pathology,
  70. (70) Department of Surgical Oncology and
  71. (71) Leiden University Medical Center, grid.10419.3d
  72. (72) Pomeranian Medical University, grid.107950.a
  73. (73) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA,
  74. (74) Pontificia Universidad Javeriana, grid.41312.35
  75. (75) University of California, Irvine, grid.266093.8
  76. (76) McGill University and Génome Québec Innovation Centre, grid.411640.6
  77. (77) QIMR Berghofer Medical Research Institute, grid.1049.c

Description

The chromosomal passenger complex (CPC) plays a pivotal role in the regulation of cell division. Therefore, inherited CPC variability could influence tumor development. The present candidate gene approach investigates the relationship between single nucleotide polymorphisms (SNPs) in genes encoding key CPC components and breast cancer risk. Fifteen SNPs in four CPC genes (INCENP, AURKB, BIRC5 and CDCA8) were genotyped in 88 911 European women from 39 case-control studies of the Breast Cancer Association Consortium. Possible associations were investigated in fixed-effects meta-analyses. The synonymous SNP rs1675126 in exon 7 of INCENP was associated with overall breast cancer risk [per A allele odds ratio (OR) 0.95, 95% confidence interval (CI) 0.92-0.98, P = 0.007] and particularly with estrogen receptor (ER)-negative breast tumors (per A allele OR 0.89, 95% CI 0.83-0.95, P = 0.0005). SNPs not directly genotyped were imputed based on 1000 Genomes. The SNPs rs1047739 in the 3' untranslated region and rs144045115 downstream of INCENP showed the strongest association signals for overall (per T allele OR 1.03, 95% CI 1.00-1.06, P = 0.0009) and ER-negative breast cancer risk (per A allele OR 1.06, 95% CI 1.02-1.10, P = 0.0002). Two genotyped SNPs in BIRC5 were associated with familial breast cancer risk (top SNP rs2071214: per G allele OR 1.12, 95% CI 1.04-1.21, P = 0.002). The data suggest that INCENP in the CPC pathway contributes to ER-negative breast cancer susceptibility in the European population. In spite of a modest contribution of CPC-inherited variants to the total burden of sporadic and familial breast cancer, their potential as novel targets for breast cancer treatment should be further investigated.

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Times Cited: 9

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Relative Citation ratio (RCR): 0.48

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