| Literature DB >> 24740199 |
Matthew S Block1, Bridget Charbonneau2, Robert A Vierkant3, Zachary Fogarty3, William R Bamlet3, Paul D P Pharoah4, Mary Anne Rossing5, Daniel Cramer6, Celeste Leigh Pearce7, Joellen Schildkraut8, Usha Menon9, Susanne K Kjaer10, Douglas A Levine11, Jacek Gronwald12, Hoda Anton Culver13, Alice S Whittemore14, Beth Y Karlan15, Diether Lambrechts16, Nicolas Wentzensen17, Jolanta Kupryjanczyk18, Jenny Chang-Claude19, Elisa V Bandera20, Estrid Hogdall21, Florian Heitz22, Stanley B Kaye23, Peter A Fasching24, Ian Campbell25, Marc T Goodman26, Tanja Pejovic27, Yukie T Bean27, Laura E Hays28, Galina Lurie29, Diana Eccles30, Alexander Hein31, Matthias W Beckmann31, Arif B Ekici32, James Paul33, Robert Brown34, James M Flanagan34, Philipp Harter22, Andreas du Bois22, Ira Schwaab35, Claus K Hogdall36, Lene Lundvall36, Sara H Olson37, Irene Orlow37, Lisa E Paddock38, Anja Rudolph19, Ursula Eilber19, Agnieszka Dansonka-Mieszkowska18, Iwona K Rzepecka18, Izabela Ziolkowska-Seta39, Louise A Brinton17, Hannah Yang17, Montserrat Garcia-Closas40, Evelyn Despierre41, Sandrina Lambrechts41, Ignace Vergote41, Christine S Walsh15, Jenny Lester15, Weiva Sieh14, Valerie McGuire14, Joseph H Rothstein14, Argyrios Ziogas13, Jan Lubiński12, Cezary Cybulski12, Janusz Menkiszak42, Allan Jensen43, Simon A Gayther7, Susan J Ramus7, Aleksandra Gentry-Maharaj9, Andrew Berchuck44, Anna H Wu7, Malcolm C Pike45, David Van Den Berg7, Kathryn L Terry6, Allison F Vitonis46, Starr M Ramirez2, David N Rider3, Keith L Knutson47, Thomas A Sellers48, Catherine M Phelan48, Jennifer A Doherty49, Sharon E Johnatty50, Anna deFazio51, Honglin Song52, Jonathan Tyrer52, Kimberly R Kalli1, Brooke L Fridley53, Julie M Cunningham54, Ellen L Goode55.
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-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. ©2014 American Association for Cancer Research.Entities:
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Year: 2014 PMID： 24740199 PMCID： PMC4082406 DOI： 10.1158/1055-9965.EPI-13-0962
Source DB: PubMed Journal: Cancer Epidemiol Biomarkers Prev ISSN： 1055-9965 Impact factor: 4.254