Block, Matthew S3; Charbonneau, Bridget3; Vierkant, Robert A3; Fogarty, Zachary3; Bamlet, William R3; Pharoah, Paul D P3; Rossing, Mary Anne3; Cramer, Daniel3; Pearce, Celeste Leigh3; Schildkraut, Joellen3; Menon, Usha3; Kjaer, Susanne K5; Levine, Douglas A3; Gronwald, Jacek3; Culver, Hoda Anton3; Whittemore, Alice S3; Karlan, Beth Y3; Lambrechts, Diether3; Wentzensen, Nicolas3; Kupryjanczyk, Jolanta3; Chang-Claude, Jenny3; Bandera, Elisa V3; Hogdall, Estrid3; Heitz, Florian3; Kaye, Stanley B3; Fasching, Peter A3; Campbell, Ian3; Goodman, Marc T3; Pejovic, Tanja3; Bean, Yukie T3; Hays, Laura E3; Lurie, Galina3; Eccles, Diana3; Hein, Alexander3; Beckmann, Matthias W3; Ekici, Arif B3; Paul, James3; Brown, Robert3; Flanagan, James M3; Harter, Philipp3; du Bois, Andreas3; Schwaab, Ira3; Hogdall, Claus K5; Lundvall, Lene3; Olson, Sara H3; Orlow, Irene3; Paddock, Lisa E3; Rudolph, Anja3; Eilber, Ursula3; Dansonka-Mieszkowska, Agnieszka3; Rzepecka, Iwona K3; Ziolkowska-Seta, Izabela3; Brinton, Louise A3; Yang, Hannah3; Garcia-Closas, Montserrat3; Despierre, Evelyn3; Lambrechts, Sandrina3; Vergote, Ignace3; Walsh, Christine S3; Lester, Jenny3; Sieh, Weiva3; McGuire, Valerie3; Rothstein, Joseph H3; Ziogas, Argyrios3; Lubiński, Jan3; Cybulski, Cezary3; Menkiszak, Janusz3; Jensen, Allan6; Gayther, Simon A3; Ramus, Susan J3; Gentry-Maharaj, Aleksandra3; Berchuck, Andrew3; Wu, Anna H3; Pike, Malcolm C3; Van Den Berg, David3; Terry, Kathryn L3; Vitonis, Allison F3; Ramirez, Starr M3; Rider, David N3; Knutson, Keith L3; Sellers, Thomas A3; Phelan, Catherine M3; Doherty, Jennifer A3; Johnatty, Sharon E3; deFazio, Anna3; Song, Honglin3; Tyrer, Jonathan3; Kalli, Kimberly R3; Fridley, Brooke L3; Cunningham, Julie M3; Goode, Ellen L3
1 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Public Health, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet5 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet6 Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet
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.
Cancer Epidemiology, Biomarkers and Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology, 2014, Vol 23, Issue 7, p. 1421-1427