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

Variation in NF- kB signaling pathways and survival in invasive epithelial ovarian cancer
Variation in NF- kB signaling pathways and survival in invasive epithelial ovarian cancer
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
1421-1427
Block, M.S.
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Charbonneau, B.
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Vierkant, R.
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Fogarty, Z.
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Bamlet, W.R.
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Pharoah, P.D.P.
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Rossing, M.A.
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Cramer, D.
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Pearce, C.L.
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Eccles, D.
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Despierre, E.
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Lambrechts, S.
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Johnatty, S.E.
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deFazio, A.
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Song, H.
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Tyrer, J.
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Kalli, K.R.
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Fridley, B.L.
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Cunningham, J.M.
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Goode, E.L.
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Block, M.S., Charbonneau, B. and Vierkant, R. et al. (2014) Variation in NF- kB signaling pathways and survival in invasive epithelial ovarian cancer. Cancer Epidemiology, Biomarkers & Prevention, 23 (7), 1421-1427. (doi:10.1158/1055-9965.EPI-13-0962). (PMID:24740199)

Record type: Article

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

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More information

Accepted/In Press date: 9 April 2014
e-pub ahead of print date: 16 April 2014
Published date: July 2014
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 382782
URI: http://eprints.soton.ac.uk/id/eprint/382782
DOI: doi:10.1158/1055-9965.EPI-13-0962
PURE UUID: fc8e6f2e-bac1-42cc-b396-295c49e224b5
ORCID for D. Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 12 Oct 2015 13:55
Last modified: 15 Mar 2024 02:40

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Contributors

Author: M.S. Block
Author: B. Charbonneau
Author: R. Vierkant
Author: Z. Fogarty
Author: W.R. Bamlet
Author: P.D.P. Pharoah
Author: M.A. Rossing
Author: D. Cramer
Author: C.L. Pearce
Author: J. Schildkraut
Author: U. Menon
Author: S.K. Kjaer
Author: D.A. Levine
Author: J. Gronwald
Author: H.A. Culver
Author: A.S. Whittemore
Author: B.Y. Karlan
Author: D. Lambrechts
Author: N. Wentzensen
Author: J. Kupryjanczyk
Author: J. Chang-Claude
Author: E.V. Bandera
Author: E. Hogdall
Author: F. Heitz
Author: S.B. Kaye
Author: P.A. Fasching
Author: I. Campbell
Author: M.T. Goodman
Author: T. Pejovic
Author: Y.T. Bean
Author: L.E. Hays
Author: G. Lurie
Author: D. Eccles ORCID iD
Author: A. Hein
Author: M.W. Beckmann
Author: A.B. Ekici
Author: J. Paul
Author: R. Brown
Author: J.M. Flanagan
Author: P. Harter
Author: A. du Bois
Author: I. Schwaab
Author: C.K. Hogdall
Author: L. Lundvall
Author: S.H. Olson
Author: I. Orlow
Author: L.E. Paddock
Author: A. Rudolph
Author: U. Eilber
Author: A. Dansonka-Mieszkowska
Author: I.K. Rzepecka
Author: I. Ziolkowska-Seta
Author: L.A. Brinton
Author: H. Yang
Author: M. Garcia-Closas
Author: E. Despierre
Author: S. Lambrechts
Author: I. Vergote
Author: C.S. Walsh
Author: J. Lester
Author: W. Sieh
Author: V. McGuire
Author: J.H. Rothstein
Author: A. Ziogas
Author: J. Lubi ski
Author: C. Cybulski
Author: J. Menkiszak
Author: A. Jensen
Author: S.A. Gayther
Author: S.J. Ramus
Author: A. Gentry-Maharaj
Author: A. Berchuck
Author: A.H. Wu
Author: M.C. Pike
Author: D. Van Den Berg
Author: K.L. Terry
Author: A.F. Vitonis
Author: S.M. Ramirez
Author: D.N. Rider
Author: K.L. Knutson
Author: T.A. Sellers
Author: C.M. Phelan
Author: J.A. Doherty
Author: S.E. Johnatty
Author: A. deFazio
Author: H. Song
Author: J. Tyrer
Author: K.R. Kalli
Author: B.L. Fridley
Author: J.M. Cunningham
Author: E.L. Goode

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