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

Matthew S Block; Bridget Charbonneau; Robert A Vierkant; Zachary Fogarty; William R Bamlet; Paul D P Pharoah; Mary Anne Rossing; Daniel Cramer; Celeste Leigh Pearce; Joellen Schildkraut; Usha Menon; Susanne K Kjaer; Douglas A Levine; Jacek Gronwald; Hoda Anton Culver; Alice S Whittemore; Beth Y Karlan; Diether Lambrechts; Nicolas Wentzensen; Jolanta Kupryjanczyk; Jenny Chang-Claude; Elisa V Bandera; Estrid Hogdall; Florian Heitz; Stanley B Kaye; Peter A Fasching; Ian Campbell; Marc T Goodman; Tanja Pejovic; Yukie T Bean; Laura E Hays; Galina Lurie; Diana Eccles; Alexander Hein; Matthias W Beckmann; Arif B Ekici; James Paul; Robert Brown; James M Flanagan; Philipp Harter; Andreas du Bois; Ira Schwaab; Claus K Hogdall; Lene Lundvall; Sara H Olson; Irene Orlow; Lisa E Paddock; Anja Rudolph; Ursula Eilber; Allan Jensen; Georgia Chenevix-Trench

doi:10.1158/1055-9965.EPI-13-0962

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

Matthew S Block, Bridget Charbonneau, Robert A Vierkant, Zachary Fogarty, William R Bamlet, Paul D P Pharoah, Mary Anne Rossing, Daniel Cramer, Celeste Leigh Pearce, Joellen Schildkraut, Usha Menon, Susanne K Kjaer, Douglas A Levine, Jacek Gronwald, Hoda Anton Culver, Alice S Whittemore, Beth Y Karlan, Diether Lambrechts, Nicolas Wentzensen, Jolanta KupryjanczykJenny Chang-Claude, Elisa V Bandera, Estrid Hogdall, Florian Heitz, Stanley B Kaye, Peter A Fasching, Ian Campbell, Marc T Goodman, Tanja Pejovic, Yukie T Bean, Laura E Hays, Galina Lurie, Diana Eccles, Alexander Hein, Matthias W Beckmann, Arif B Ekici, James Paul, Robert Brown, James M Flanagan, Philipp Harter, Andreas du Bois, Ira Schwaab, Claus K Hogdall, Lene Lundvall, Sara H Olson, Irene Orlow, Lisa E Paddock, Anja Rudolph, Ursula Eilber, Allan Jensen, Georgia Chenevix-Trench

11 Citations (Scopus)

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-kB (NF-kB) 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-kB 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.

Original language	English
Journal	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume	23
Issue number	7
Pages (from-to)	1421-1427
Number of pages	7
ISSN	1055-9965
DOIs	https://doi.org/10.1158/1055-9965.EPI-13-0962
Publication status	Published - Jul 2014

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10.1158/1055-9965.EPI-13-0962

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Block, M. S., Charbonneau, B., Vierkant, R. A., Fogarty, Z., Bamlet, W. R., Pharoah, P. D. P., Rossing, M. A., Cramer, D., 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., ... Georgia Chenevix-Trench (2014). Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 23(7), 1421-1427. https://doi.org/10.1158/1055-9965.EPI-13-0962

Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer. / Block, Matthew S; Charbonneau, Bridget; Vierkant, Robert A et al.
In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Vol. 23, No. 7, 07.2014, p. 1421-1427.

Research output: Contribution to journal › Letter › peer-review

Block, MS, Charbonneau, B, Vierkant, RA, Fogarty, Z, Bamlet, WR, Pharoah, PDP, 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, Jensen, A & Georgia Chenevix-Trench 2014, 'Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer', Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, vol. 23, no. 7, pp. 1421-1427. https://doi.org/10.1158/1055-9965.EPI-13-0962

Block MS, Charbonneau B, Vierkant RA, Fogarty Z, Bamlet WR, Pharoah PDP et al. Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2014 Jul;23(7):1421-1427. doi: 10.1158/1055-9965.EPI-13-0962

Block, Matthew S ; Charbonneau, Bridget ; Vierkant, Robert A et al. / Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer. In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2014 ; Vol. 23, No. 7. pp. 1421-1427.

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title = "Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer",

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-kB (NF-kB) 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-kB 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.",

author = "Block, {Matthew S} and Bridget Charbonneau and Vierkant, {Robert A} and Zachary Fogarty and Bamlet, {William R} and Pharoah, {Paul D P} and Rossing, {Mary Anne} and Daniel Cramer and Pearce, {Celeste Leigh} and Joellen Schildkraut and Usha Menon and Kjaer, {Susanne K} and Levine, {Douglas A} and Jacek Gronwald and Culver, {Hoda Anton} and Whittemore, {Alice S} and Karlan, {Beth Y} and Diether Lambrechts and Nicolas Wentzensen and Jolanta Kupryjanczyk and Jenny Chang-Claude and Bandera, {Elisa V} and Estrid Hogdall and Florian Heitz and Kaye, {Stanley B} and Fasching, {Peter A} and Ian Campbell and Goodman, {Marc T} and Tanja Pejovic and Bean, {Yukie T} and Hays, {Laura E} and Galina Lurie and Diana Eccles and Alexander Hein and Beckmann, {Matthias W} and Ekici, {Arif B} and James Paul and Robert Brown and Flanagan, {James M} and Philipp Harter and {du Bois}, Andreas and Ira Schwaab and Hogdall, {Claus K} and Lene Lundvall and Olson, {Sara H} and Irene Orlow and Paddock, {Lisa E} and Anja Rudolph and Ursula Eilber and Allan Jensen and {Georgia Chenevix-Trench}",

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T1 - Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer

AU - Block, Matthew S

AU - Charbonneau, Bridget

AU - Vierkant, Robert A

AU - Fogarty, Zachary

AU - Bamlet, William R

AU - Pharoah, Paul D P

AU - Rossing, Mary Anne

AU - Cramer, Daniel

AU - Pearce, Celeste Leigh

AU - Schildkraut, Joellen

AU - Menon, Usha

AU - Kjaer, Susanne K

AU - Levine, Douglas A

AU - Gronwald, Jacek

AU - Culver, Hoda Anton

AU - Whittemore, Alice S

AU - Karlan, Beth Y

AU - Lambrechts, Diether

AU - Wentzensen, Nicolas

AU - Kupryjanczyk, Jolanta

AU - Chang-Claude, Jenny

AU - Bandera, Elisa V

AU - Hogdall, Estrid

AU - Heitz, Florian

AU - Kaye, Stanley B

AU - Fasching, Peter A

AU - Campbell, Ian

AU - Goodman, Marc T

AU - Pejovic, Tanja

AU - Bean, Yukie T

AU - Hays, Laura E

AU - Lurie, Galina

AU - Eccles, Diana

AU - Hein, Alexander

AU - Beckmann, Matthias W

AU - Ekici, Arif B

AU - Paul, James

AU - Brown, Robert

AU - Flanagan, James M

AU - Harter, Philipp

AU - du Bois, Andreas

AU - Schwaab, Ira

AU - Hogdall, Claus K

AU - Lundvall, Lene

AU - Olson, Sara H

AU - Orlow, Irene

AU - Paddock, Lisa E

AU - Rudolph, Anja

AU - Eilber, Ursula

AU - Jensen, Allan

AU - Georgia Chenevix-Trench

PY - 2014/7

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N2 - 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-kB (NF-kB) 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-kB 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.

AB - 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-kB (NF-kB) 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-kB 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.

U2 - 10.1158/1055-9965.EPI-13-0962

DO - 10.1158/1055-9965.EPI-13-0962

M3 - Letter

C2 - 24740199

SN - 1055-9965

VL - 23

SP - 1421

EP - 1427

JO - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

IS - 7

ER -

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

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