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Variation in NF-κB signaling pathways and survival in invasive epithelial ovarian cancer.
- Source :
-
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2014 Jul; Vol. 23 (7), pp. 1421-7. Date of Electronic Publication: 2014 Apr 16. - Publication Year :
- 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 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.<br /> (©2014 American Association for Cancer Research.)
- Subjects :
- Adult
Aged
Carcinoma, Ovarian Epithelial
Female
Genotype
Humans
Middle Aged
Neoplasm Invasiveness
Neoplasms, Glandular and Epithelial pathology
Ovarian Neoplasms pathology
Polymorphism, Single Nucleotide
Proportional Hazards Models
NF-kappa B genetics
Neoplasms, Glandular and Epithelial genetics
Neoplasms, Glandular and Epithelial mortality
Ovarian Neoplasms genetics
Ovarian Neoplasms mortality
Signal Transduction genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7755
- Volume :
- 23
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 24740199
- Full Text :
- https://doi.org/10.1158/1055-9965.EPI-13-0962