Article open access publication

Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium

Human Genetics, Springer Nature, ISSN 0340-6717

Volume 135, 1, 2016

DOI:10.1007/s00439-015-1616-8, Dimensions: pub.1051869077, PMC: PMC4698282, PMID: 26621531,

Authors

Wang, Qin (4)
Benitez, Javier (5) (6)
Marmé, Frederik (14) (15)
Guénel, Pascal (16) (17)
Truong, Thérèse (16) (17)
Bojesen, Stig E. (18) (19)
Brenner, Hermann (1) (23)
Brauch, Hiltrud (1) (27) (28)
Mannermaa, Arto (31) (32)
Giles, Graham G (7) (40)
Milne, Roger L. (7) (40)
Kristensen, Vessela (44) (45) (46)
Zheng, Wei (47)
Winqvist, Robert (48) (49)
Andrulis, Irene L. (51) (52)
Hall, Per (55)
Torres, Diana (1) (57)
Chang-Claude, Jenny * (1) (59)

* Corresponding author

Affiliations

Organisations

  1. (1) German Cancer Research Center, grid.7497.d
  2. (2) Roswell Park Cancer Institute, grid.240614.5
  3. (3) Mayo Clinic, grid.66875.3a
  4. (4) University of Cambridge, grid.5335.0
  5. (5) Centro de Investigación en Red de Enfermedades Raras, Valencia, Spain
  6. (6) Spanish National Cancer Research Centre, grid.7719.8
  7. (7) University of Melbourne, grid.1008.9
  8. (8) Antoni van Leeuwenhoek Hospital, grid.430814.a
  9. (9) University of California, Los Angeles, grid.19006.3e
  10. (10) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  11. (11) London School of Hygiene & Tropical Medicine, grid.8991.9
  12. (12) King's College London, grid.13097.3c
  13. (13) University of Oxford, grid.4991.5
  14. (14) Heidelberg University, grid.7700.0
  15. (15) National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
  16. (16) French Institute of Health and Medical Research, grid.7429.8
  17. (17) University of Paris-Sud, grid.5842.b
  18. (18) Herlev Hospital, grid.411900.d, Capital Region
  19. (19) University of Copenhagen, grid.5254.6, KU
  20. (20) Hospital Monte Naranco, grid.414858.4
  21. (21) University of California, Irvine, grid.266093.8
  22. (22) City Of Hope National Medical Center, grid.410425.6
  23. (23) University Hospital Heidelberg, grid.5253.1
  24. (24) Technical University of Munich, grid.6936.a
  25. (25) University Hospital Cologne, grid.411097.a
  26. (26) University of Cologne, grid.6190.e
  27. (27) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  28. (28) University of Tübingen, grid.10392.39
  29. (29) Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  30. (30) Hannover Medical School, grid.10423.34
  31. (31) Kuopio University Hospital, grid.410705.7
  32. (32) University of Eastern Finland, grid.9668.1
  33. (33) QIMR Berghofer Medical Research Institute, grid.1049.c
  34. (34) Peter MacCallum Cancer Centre, grid.1055.1
  35. (35) KU Leuven, grid.5596.f
  36. (36) Multidisciplinary Breast Center, University Hospitals Leuven, University of Leuven, Leuven, Belgium
  37. (37) University Medical Center Hamburg-Eppendorf, grid.13648.38
  38. (38) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  39. (39) IFOM, Fondazione Istituto FIRC (Italian Foundation of Cancer Research) di Oncologia Molecolare, Milan, Italy
  40. (40) Cancer Council Victoria, grid.3263.4
  41. (41) University of Southern California, grid.42505.36
  42. (42) Laval University, grid.23856.3a
  43. (43) McGill University, grid.14709.3b
  44. (44) Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
  45. (45) K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  46. (46) Oslo University Hospital, grid.55325.34
  47. (47) Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
  48. (48) Central Finland Health Care District, grid.460356.2
  49. (49) University of Oulu, grid.10858.34
  50. (50) Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
  51. (51) University of Toronto, grid.17063.33
  52. (52) Lunenfeld-Tanenbaum Research Institute, grid.250674.2
  53. (53) National Cancer Institute, grid.48336.3a
  54. (54) Institute of Cancer Research, grid.18886.3f
  55. (55) Karolinska Institute, grid.4714.6
  56. (56) University of Sheffield, grid.11835.3e
  57. (57) Pontificia Universidad Javeriana, grid.41312.35
  58. (58) Pomeranian Medical University, grid.107950.a
  59. (59) University Cancer Center Hamburg, grid.412315.0

Description

Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.

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Research area: Medicine

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Research area: Medicine

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Times Cited: 5

Field Citation Ratio (FCR): 1.04

Relative Citation ratio (RCR): 0.28

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