||Block MS, Charbonneau B, Vierkant RA, Fogarty Z, Bamlet WR, Pharoah PD, Georgia Chenevix-Trench, for AOCS, /ACS Group, Rossing MA, Cramer D, Pearce CL, Schildkraut J, Menon U, Kjaer SK, Levine DA, Gronwald J, Culver HA, Whittemore AS, Karlan BY, Lambrechts D, Wentzensen N, Kupryjanczyk J, Chang-Claude J, Bandera EV, Hogdall E, Heitz F, Kaye SB, Fasching PA, Campbell I, Goodman MT, Pejovic T, Bean YT, Hays LE, Lurie G, Eccles D, Hein A, Beckmann MW, Ekici AB, Paul J, Brown R, Flanagan JM, Harter P, du Bois A, Schwaab I, Hogdall CK, Lundvall L, Olson SH, Orlow I, Paddock LE, Rudolph A, Eilber U, Dansonka-Mieszkowska A, Rzepecka IK, Ziolkowska-Seta I, Brinton LA, Yang H, Garcia-Closas M, Despierre E, Lambrechts S, Vergote I, Walsh CS, Lester J, Sieh W, McGuire V, Rothstein JH, Ziogas A, Lubiński J, Cybulski C, Menkiszak J, Jensen A, Gayther SA, Ramus SJ, Gentry-Maharaj A, Berchuck A, Wu AH, Pike MC, Van Den Berg D, Terry KL, Vitonis AF, Ramirez SM, Rider DN, Knutson KL, Sellers TA, Phelan CM, Doherty JA, Johnatty SE, deFazio A, Song H, Tyrer J, Kalli KR, Fridley BL, Cunningham JM, Goode EL
||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.