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

Publikation: Bidrag til tidsskriftLetterForskningfagfællebedømt

  • Matthew S Block
  • Bridget Charbonneau
  • Robert A Vierkant
  • Zachary Fogarty
  • William R Bamlet
  • Paul D P Pharoah
  • Mary Anne Rossing
  • Daniel Cramer
  • Celeste Leigh Pearce
  • Joellen Schildkraut
  • Usha Menon
  • Kjær, Susanne Krüger
  • Douglas A Levine
  • Jacek Gronwald
  • Hoda Anton Culver
  • Alice S Whittemore
  • Beth Y Karlan
  • Diether Lambrechts
  • Nicolas Wentzensen
  • Jolanta Kupryjanczyk
  • Jenny Chang-Claude
  • Elisa V Bandera
  • Estrid Hogdall
  • Florian Heitz
  • Stanley B Kaye
  • Peter A Fasching
  • Ian Campbell
  • Marc T Goodman
  • Tanja Pejovic
  • Yukie T Bean
  • Laura E Hays
  • Galina Lurie
  • Diana Eccles
  • Alexander Hein
  • Matthias W Beckmann
  • Arif B Ekici
  • James Paul
  • Robert Brown
  • James M Flanagan
  • Philipp Harter
  • Andreas du Bois
  • Ira Schwaab
  • Høgdall, Claus Kim
  • Lene Lundvall
  • Sara H Olson
  • Irene Orlow
  • Lisa E Paddock
  • Anja Rudolph
  • Ursula Eilber
  • Allan Jensen
  • Georgia Chenevix-Trench

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.

OriginalsprogEngelsk
TidsskriftCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Vol/bind23
Udgave nummer7
Sider (fra-til)1421-1427
Antal sider7
ISSN1055-9965
DOI
StatusUdgivet - jul. 2014

ID: 138498614