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

Matthew S. Block, Bridget Charbonneau, Robert A. Vierkant, Zachary Fogarty, William R. Bamlet, Paul D.P. Pharoah, Georgia Chenevix-Trench, Mary Anne Rossing, Daniel Cramer, Celeste Leigh Pearce, Joellen Schildkraut, Usha Menon, Susanne K. Kjaer, Douglas A. Levine, Jacek Gronwald, Hoda Anton Culver, Alice S. Whittemore, Beth Y. Karlan, Diether Lambrechts, Nicolas WentzensenJolanta 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, Claus K. Hogdall, Lene Lundvall, Sara H. Olson, Irene Orlow, Lisa E. Paddock, Anja Rudolph, Ursula Eilber, Agnieszka Dansonka-Mieszkowska, Iwona K. Rzepecka, Izabela Ziolkowska-Seta, Louise A. Brinton, Hannah Yang, Montserrat Garcia-Closas, Evelyn Despierre, Sandrina Lambrechts, Ignace Vergote, Christine S. Walsh, Jenny Lester, Weiva Sieh, Valerie McGuire, Joseph H. Rothstein, Argyrios Ziogas, Jan Lubinski, Cezary Cybulski, Janusz Menkiszak, Allan Jensen, Simon A. Gayther, Susan J. Ramus, Aleksandra Gentry-Maharaj, Andrew Berchuck, Anna H. Wu, Malcolm C. Pike, David Van Den Berg, Kathryn L. Terry, Allison F. Vitonis, Starr M. Ramirez, David N. Rider, Keith L. Knutson, Thomas A. Sellers, Catherine M. Phelan, Jennifer A. Doherty, Sharon E. Johnatty, Anna De Fazio, Honglin Song, Jonathan Tyrer, Kimberly R. Kalli, Brooke L. Fridley, Julie M. Cunningham, Ellen L. Goode

Research output: Contribution to journalArticle

11 Scopus citations

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-kB (NF-kB) 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-kB 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.

Original languageEnglish (US)
Pages (from-to)1421-1427
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume23
Issue number7
DOIs
StatePublished - Jul 2014

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Block, M. S., Charbonneau, B., Vierkant, R. A., Fogarty, Z., Bamlet, W. R., Pharoah, P. D. P., Chenevix-Trench, G., Rossing, M. A., Cramer, D., Pearce, C. L., Schildkraut, J., Menon, U., Kjaer, S. K., Levine, D. A., Gronwald, J., Culver, H. A., Whittemore, A. S., Karlan, B. Y., Lambrechts, D., ... Goode, E. L. (2014). Variation in NF-κB signaling pathways and survival in invasive epithelial ovarian cancer. Cancer Epidemiology Biomarkers and Prevention, 23(7), 1421-1427. https://doi.org/10.1158/1055-9965.EPI-13-0962