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

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

Authors :
Block, M. S.
Charbonneau, B.
Vierkant, R. A.
Fogarty, Z.
Bamlet, W. R.
Pharoah, P. D. P.
Rossing, M. A.
Cramer, Daniel William
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.
Wentzensen, N.
Kupryjanczyk, J.
Chang-Claude, J.
Bandera, E. V.
Hogdall, E.
Heitz, F.
Kaye, S. B.
Fasching, P. A.
Campbell, I.
Goodman, M. T.
Pejovic, T.
Bean, Y. T.
Hays, L. E.
Lurie, G.
Eccles, D.
Hein, A.
Beckmann, M. W.
Ekici, A. B.
Paul, J.
Brown, R.
Flanagan, J. M.
Harter, P.
du Bois, A.
Schwaab, I.
Hogdall, C. K.
Lundvall, L.
Olson, S. H.
Orlow, I.
Paddock, L. E.
Rudolph, A.
Eilber, U.
Dansonka-Mieszkowska, A.
Rzepecka, I. K.
Ziolkowska-Seta, I.
Brinton, L. A.
Yang, H.
Garcia-Closas, M.
Despierre, E.
Lambrechts, S.
Vergote, I.
Walsh, C. S.
Lester, J.
Sieh, W.
McGuire, V.
Rothstein, J. H.
Ziogas, A.
Lubi ski, J.
Cybulski, C.
Menkiszak, J.
Jensen, A.
Gayther, S. A.
Ramus, S. J.
Gentry-Maharaj, A.
Berchuck, A.
Wu, A. H.
Pike, M. C.
Van Den Berg, D.
Terry, Kathryn Lynne
Vitonis, A. F.
Ramirez, S. M.
Rider, D. N.
Knutson, K. L.
Sellers, T. A.
Phelan, C. M.
Doherty, J. A.
Johnatty, S. E.
deFazio, A.
Song, H.
Tyrer, J.
Kalli, K. R.
Fridley, B. L.
Cunningham, J. M.
Goode, E. L.
Source :
Block, M. S., B. Charbonneau, R. A. Vierkant, Z. Fogarty, W. R. Bamlet, P. D. P. Pharoah, M. A. Rossing, et al. 2014. “Variation in NF- B Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer.” Cancer Epidemiology Biomarkers & Prevention 23 (7) (April 16): 1421–1427. doi:10.1158/1055-9965.epi-13-0962.
Publication Year :
2014
Publisher :
American Association for Cancer Research (AACR), 2014.

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 < 2.5×10−5). 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=4.13×10−6) 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=2.33×10−5). 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=6.49×10−5) and PLCG1 (phospholipase C, gamma 1) rs11696662 in patients with clear cell EOC (HR 0.43, 95% CI 0.26–0.73, p=4.56×10−4). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies.

Details

Language :
English
ISSN :
10559965
Database :
Digital Access to Scholarship at Harvard (DASH)
Journal :
Block, M. S., B. Charbonneau, R. A. Vierkant, Z. Fogarty, W. R. Bamlet, P. D. P. Pharoah, M. A. Rossing, et al. 2014. “Variation in NF- B Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer.” Cancer Epidemiology Biomarkers & Prevention 23 (7) (April 16): 1421–1427. doi:10.1158/1055-9965.epi-13-0962.
Publication Type :
Academic Journal
Accession number :
edshld.1.27336522
Document Type :
Journal Article
Full Text :
https://doi.org/10.1158/1055-9965.EPI-13-0962