Variation in NF-?B signaling pathways and survival in invasive epithelial ovarian cancer

Block MS, Charbonneau B, Vierkant RA, Fogarty Z, Bamlet WR, Pharoah PDP, Chenevix-Trench G, Rossing MA, Cramer D, Pearce CL, Schildkraut J, Menon U, Kjaer SK, Levine DA, Gronwald J, Culver HA, Whittemore AS, Karlan BY, Lambrechts D, Wentzensen N, Kupryjanczyk J, Chang-Claude J, Bandera EV, Hogdall E, Heitz F, Kaye SB, Fasching PA, Campbell I, Goodman MT, Pejovic T, Bean YT, Hays LE, Lurie G, Eccles D, Hein A, Beckmann M, Ekici AB, Paul J, Brown R, Flanagan JM, Harter P, Du Bois A, Schwaab I, Hogdall CK, Lundvall L, Olson SH, Orlow I, Paddock LE, Rudolph A, Eilber U, Dansonka-Mieszkowska A, Rzepecka IK, Ziolkowska-Seta I, Brinton LA, Yang H, Garcia-Closas M, Despierre E, Lambrechts S, Vergote I, Walsh CS, Lester J, Sieh W, Mcguire V, Rothstein JH, Ziogas A, Lubinski J, Cybulski C, Menkiszak J, Jensen A, Gayther SA, Ramus SJ, Gentry-Maharaj A, Berchuck A, Wu AH, Pike MC, Van Den Berg D, Terry KL, Vitonis AF, Ramirez SM, Rider DN, Knutson KL, Sellers TA, Phelan CM, Doherty JA, Johnatty SE, Defazio A, Song H, Tyrer J, Kalli KR, Fridley BL, Cunningham JM, Goode EL (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 23

Pages Range: 1421-7

Journal Issue: 7

DOI: 10.1158/1055-9965.EPI-13-0962

Abstract

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-?B (NF-?B) 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-?B 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.

Authors with CRIS profile

Involved external institutions

Mayo Clinic United States (USA) (US) Institut für Humangenetik Wiesbaden Germany (DE) University of Washington United States (USA) (US) University of Cambridge United Kingdom (GB) Rigshospitalet Denmark (DK) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) Memorial Sloan Kettering Cancer Center United States (USA) (US) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University of Southern California (USC) United States (USA) (US) Duke University United States (USA) (US) University of California Irvine United States (USA) (US) University of Copenhagen Denmark (DK) Cedars-Sinai Medical Center United States (USA) (US) HELIOS Kliniken Germany (DE) Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust United Kingdom (GB) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB) New Jersey, Department of Health United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) The Institute of Cancer Research (ICR) United Kingdom (GB) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) National Cancer Institute (NCI) United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) Peter MacCallum Cancer Centre Australia (AU) University of California Los Angeles (UCLA) United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) University of Sydney (USYD) Australia (AU) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University College London (UCL) United Kingdom (GB) Stanford University United States (USA) (US) Oregon Health and Science University (OSHU) United States (USA) (US) University of Medicine and Dentistry of New Jersey (UMDNJ) United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Dartmouth College United States (USA) (US) University of Kansas (KU) United States (USA) (US) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University of Southampton United Kingdom (GB)

How to cite

APA:

Block, M.S., Charbonneau, B., Vierkant, R.A., Fogarty, Z., Bamlet, W.R., Pharoah, P.D.P.,... Goode, E.L. (2014). Variation in NF-?B signaling pathways and survival in invasive epithelial ovarian cancer. Cancer Epidemiology Biomarkers & Prevention, 23(7), 1421-7. https://dx.doi.org/10.1158/1055-9965.EPI-13-0962

MLA:

Block, Matthew S., et al. "Variation in NF-?B signaling pathways and survival in invasive epithelial ovarian cancer." Cancer Epidemiology Biomarkers & Prevention 23.7 (2014): 1421-7.

BibTeX: Download