Article open access publication

Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer

Cancer Epidemiology Biomarkers & Prevention, American Association for Cancer Research (AACR), ISSN 1055-9965

Volume 23, 7, 2014

DOI:10.1158/1055-9965.epi-13-0962, Dimensions: pub.1012890917, PMC: PMC4082406, PMID: 24740199,

Authors

AOCS, for (6) (7)
Cramer, Daniel (10) (11)
Kjaer, Susanne K. (16) (17)
Hogdall, Estrid (16) (29)
Heitz, Florian (30) (31)
Fasching, Peter A. (33) (34)
Campbell, Ian (7) (35)
Pejovic, Tanja (37) (38)
Bean, Yukie T (37) (38)
Harter, Philipp (30) (31)
du Bois, Andreas (30) (31)
Wu, Anna H (12)
Pike, Malcolm C (12) (46)
Terry, Kathryn L (10) (11)

Affiliations

Organisations

  1. (1) Authors' Affiliations: Departments of Medical Oncology,
  2. (2) Health Sciences Research, Division of Epidemiology;
  3. (3) Health Sciences Research, Division of Biomedical Statistics and Informatics;
  4. (4) University of Cambridge, grid.5335.0
  5. (5) Oncology and
  6. (6) QIMR Berghofer Medical Research Institute, grid.1049.c
  7. (7) Peter MacCallum Cancer Centre, grid.1055.1
  8. (8) Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center;
  9. (9) University of Washington, grid.34477.33
  10. (10) Harvard University, grid.38142.3c
  11. (11) Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School;
  12. (12) Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center;
  13. (13) Cancer Prevention, Detection, and Control Research Program, Duke Cancer Institute;
  14. (14) Department of Community and Family Medicine;
  15. (15) Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London;
  16. (16) Virus, Lifestyle and Genes, Danish Cancer Society Research Center;
  17. (17) Rigshospitalet, grid.475435.4, Capital Region
  18. (18) Gynecology Service, Department of Surgery;
  19. (19) Pomeranian Medical University, grid.107950.a
  20. (20) University of California, Irvine, grid.266093.8
  21. (21) Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Palo Alto;
  22. (22) Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute;
  23. (23) KU Leuven, grid.5596.f
  24. (24) Vesalius Research Center, VIB;
  25. (25) National Cancer Institute, grid.48336.3a
  26. (26) Pathology and
  27. (27) German Cancer Research Center, grid.7497.d
  28. (28) Rutgers, The State University of New Jersey, grid.430387.b
  29. (29) University of Copenhagen, grid.5254.6, KU
  30. (30) Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden;
  31. (31) Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen; and
  32. (32) Division of Clinical Studies, The Institute of Cancer Research and the Royal Marsden Hospital;
  33. (33) University of California, Los Angeles, grid.19006.3e
  34. (34) University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen;
  35. (35) University of Melbourne, grid.1008.9
  36. (36) Cedars-Sinai Medical Center, grid.50956.3f
  37. (37) Department of Obstetrics and Gynecology,
  38. (38) Oregon Health & Science University, grid.5288.7
  39. (39) Department of Hematology and Oncology and the Knight Cancer Institute, Portland, Oregon;
  40. (40) University of Hawaii at Manoa, grid.410445.0
  41. (41) Faculty of Medicine, University of Southampton, University Hospital Southampton;
  42. (42) University of Erlangen-Nuremberg, grid.5330.5
  43. (43) Beatson West of Scotland Cancer Centre, grid.422301.6
  44. (44) Department of Surgery and Cancer, Imperial College London;
  45. (45) Institut für Humangenetik Wiesbaden, Wiesbaden;
  46. (46) Memorial Sloan Kettering Cancer Center, grid.51462.34
  47. (47) New Jersey Department of Health and Senior Services, grid.238434.a
  48. (48) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  49. (49) Breast Cancer Now, grid.458394.7
  50. (50) Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton;
  51. (51) Universitair Ziekenhuis Leuven, grid.410569.f
  52. (52) Duke University Hospital, grid.189509.c
  53. (53) Immunology; and
  54. (54) Moffitt Cancer Center, grid.468198.a
  55. (55) Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire;
  56. (56) Department of Gynaecological Oncology, Westmead Hospital and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead, Australia;
  57. (57) University of Kansas Medical Center, grid.412016.0
  58. (58) Mayo Clinic, grid.66875.3a

Description

Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that affect prognosis are not known. The nuclear factor-κB (NF-κB) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-κB family in 10,084 patients with invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance, P < 2.5 × 10(-5)). Results were statistically significant when assessed for patients of a single histology. Key associations were with caspase recruitment domain family, member 11 (CARD11) rs41324349 in patients with mucinous EOC [HR, 1.82; 95% confidence interval (CI), 1.41-2.35; P = 4.13 × 10(-6)] and tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B) rs7501462 in patients with endometrioid EOC (HR, 0.68; 95% CI, 0.56-0.82; P = 2.33 × 10(-5)). Other associations of note included TNF receptor-associated factor 2 (TRAF2) rs17250239 in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77-0.92; P = 6.49 × 10(-5)) and phospholipase C, gamma 1 (PLCG1) rs11696662 in patients with clear cell EOC (HR, 0.43; 95% CI, 0.26-0.73; P = 4.56 × 10(-4)). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies.

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Times Cited: 10

Field Citation Ratio (FCR): 1.79

Relative Citation ratio (RCR): 0.45

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