Title: Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer
Authors: Block, Matthew S ×
Charbonneau, Bridget
Vierkant, Robert A
Fogarty, Zachary
Bamlet, William R
Pharoah, Paul D P
Chenevix-Trench, Georgia
Rossing, Mary Anne
Cramer, Daniel
Pearce, Celeste Leigh
Schildkraut, Joellen
Menon, Usha
Kjaer, Susanne K
Levine, Douglas A
Gronwald, Jacek
Anton-Culver, Hoda
Whittemore, Alice S
Karlan, Beth Y
Lambrechts, Diether
Wentzensen, Nicolas
Kupryjanczyk, Jolanta
Chang-Claude, Jenny
Bandera, Elisa V
Hogdall, Estrid
Heitz, Florian
Kaye, Stanley B
Fasching, Peter A
Campbell, Ian
Goodman, Marc T
Pejovic, Tanja
Bean, Yukie T
Hays, Laura
Lurie, Galina
Eccles, Diana M
Hein, Alexander
Beckmann, Matthias W
Ekici, Arif B
Paul, James
Brown, Robert
Flanagan, James M
Harter, Philipp
du Bois, Andreas
Schwaab, Ira
Hogdall, Claus K
Lundvall, Lene
Olson, Sara H
Orlow, Irene
Paddock, Lisa E
Rudolph, Anja
Eilber, Ursula
Dansonka-Mieszkowska, Agnieszka
Rzepecka, Iwona K
Ziolkowska-Seta, Izabela
Brinton, Louise A
Yang, Hannah
Garcia-Closas, Montserrat
Despierre, Evelyn
Lambrechts, Sandrina
Vergote, Ignace
Walsh, Christine S
Lester, Jenny
Sieh, Weiva
McGuire, Valerie
Rothstein, Joseph H
Ziogas, Argyrios
Lubinski, Jan
Cybulski, Cezary
Menkiszak, Janusz
Jensen, Allan
Gayther, Simon A
Ramus, Susan J
Gentry-Maharaj, Aleksandra
Berchuck, Andrew
Wu, Anna H
Pike, Malcolm C
Van Den Berg, David J
Terry, Kathryn L
Vitonis, Allison F
Ramirez, Starr M
Rider, David N
Knutson, Keith L
Sellers, Thomas A
Phelan, Catherine M
Doherty, Jennifer A
Johnatty, Sharon E
Defazio, Anna
Song, Honglin
Tyrer, Jonathan
Kalli, Kimberly R
Fridley, Brooke L
Cunningham, Julie M
Goode, Ellen L #
Issue Date: Jul-2014
Publisher: American Association for Cancer Research
Series Title: Cancer Epidemiology, Biomarkers & Prevention vol:23 issue:7 pages:1421-1427
Abstract: Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that impact prognosis are not known. The nuclear factor-kappa B (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 < 2.5x10-5). Results were statistically significant when assessed for patients of a single histology. Key associations were with CARD11 (caspase recruitment domain family, member 11) rs41324349 in patients with mucinous EOC (HR 1.82, 95% CI 1.41-2.35, p=4.13x10-6) and TNFRSF13B (tumor necrosis factor receptor superfamily, member 13B) rs7501462 in patients with endometrioid EOC (HR 0.68, 95% CI 0.56-0.82, p=2.33x10-5). Other associations of note included TRAF2 (TNF receptor-associated factor 2) rs17250239 in patients with high-grade serous EOC (HR 0.84, 95% CI 0.77-0.92, p=6.49x10-5) and PLCG1 (phospholipase C, gamma 1) rs11696662 in patients with clear cell EOC (HR 0.43, 95% CI 0.26-0.73, p=4.56x10-4). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies.
ISSN: 1055-9965
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gynaecological Oncology
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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