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, Georgia Chenevix-Trench, 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 WentzensenJolanta 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, Agnieszka Dansonka-Mieszkowska, Iwona K. Rzepecka, Izabela Ziolkowska-Seta, Louise A. Brinton, Hannah Yang, Montserrat Garcia-Closas, Evelyn Despierre, Sandrina Lambrechts, Ignace Vergote, Christine S. Walsh, Jenny Lester, Weiva Sieh, Valerie McGuire, Joseph H. Rothstein, Argyrios Ziogas, Jan Lubinski, Cezary Cybulski, Janusz Menkiszak, Allan Jensen, Simon A. Gayther, Susan J. Ramus, Aleksandra Gentry-Maharaj, Andrew Berchuck, Anna H. Wu, Malcolm C. Pike, David Van Den Berg, Kathryn L. Terry, Allison F. Vitonis, Starr M. Ramirez, David N. Rider, Keith L Knutson, Thomas A. Sellers, Catherine M. Phelan, Jennifer A. Doherty, Sharon E. Johnatty, Anna De Fazio, Honglin Song, Jonathan Tyrer, Kimberly R. Kalli, Brooke L. Fridley, Julie M Cunningham, Ellen L Goode

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1421-1427
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume23
Issue number7
DOIs
StatePublished - 2014

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Survival
Confidence Intervals
Histology
Transmembrane Activator and CAML Interactor Protein
Immunity
TNF Receptor-Associated Factor 2
Phospholipase C gamma
Inflammation
Ovarian epithelial cancer
Ovarian Neoplasms
Genes
Transcription Factors
Genotype
Neoplasms

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Variation in NF-κB signaling pathways and survival in invasive epithelial ovarian cancer. / Block, Matthew S; Charbonneau, Bridget; Vierkant, Robert A.; Fogarty, Zachary; Bamlet, William R.; Pharoah, Paul D P; Chenevix-Trench, Georgia; Rossing, Mary Anne; Cramer, Daniel; Pearce, Celeste Leigh; Schildkraut, Joellen; Menon, Usha; Kjaer, Susanne K.; Levine, Douglas A.; Gronwald, Jacek; Culver, Hoda Anton; Whittemore, Alice S.; Karlan, Beth Y.; Lambrechts, Diether; Wentzensen, Nicolas; Kupryjanczyk, Jolanta; Chang-Claude, Jenny; Bandera, Elisa V.; Hogdall, Estrid; Heitz, Florian; Kaye, Stanley B.; Fasching, Peter A.; Campbell, Ian; Goodman, Marc T.; Pejovic, Tanja; Bean, Yukie T.; Hays, Laura E.; Lurie, Galina; Eccles, Diana; Hein, Alexander; Beckmann, Matthias W.; Ekici, Arif B.; Paul, James; Brown, Robert; Flanagan, James M.; Harter, Philipp; Du Bois, Andreas; Schwaab, Ira; Hogdall, Claus K.; Lundvall, Lene; Olson, Sara H.; Orlow, Irene; Paddock, Lisa E.; Rudolph, Anja; Eilber, Ursula; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K.; Ziolkowska-Seta, Izabela; Brinton, Louise A.; Yang, Hannah; Garcia-Closas, Montserrat; Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace; Walsh, Christine S.; Lester, Jenny; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.; Ziogas, Argyrios; Lubinski, Jan; Cybulski, Cezary; Menkiszak, Janusz; Jensen, Allan; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Berchuck, Andrew; Wu, Anna H.; Pike, Malcolm C.; Van Den Berg, David; Terry, Kathryn L.; Vitonis, Allison F.; Ramirez, Starr M.; Rider, David N.; Knutson, Keith L; Sellers, Thomas A.; Phelan, Catherine M.; Doherty, Jennifer A.; Johnatty, Sharon E.; De Fazio, Anna; Song, Honglin; Tyrer, Jonathan; Kalli, Kimberly R.; Fridley, Brooke L.; Cunningham, Julie M; Goode, Ellen L.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 23, No. 7, 2014, p. 1421-1427.

Research output: Contribution to journalArticle

Block, MS, Charbonneau, B, Vierkant, RA, Fogarty, Z, Bamlet, WR, Pharoah, PDP, Chenevix-Trench, G, 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, Lubinski, 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, De Fazio, A, Song, H, Tyrer, J, Kalli, KR, Fridley, BL, Cunningham, JM & Goode, EL 2014, 'Variation in NF-κB signaling pathways and survival in invasive epithelial ovarian cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 23, no. 7, pp. 1421-1427. https://doi.org/10.1158/1055-9965.EPI-13-0962
Block, Matthew S ; Charbonneau, Bridget ; Vierkant, Robert A. ; Fogarty, Zachary ; Bamlet, William R. ; Pharoah, Paul D P ; Chenevix-Trench, Georgia ; Rossing, Mary Anne ; Cramer, Daniel ; Pearce, Celeste Leigh ; Schildkraut, Joellen ; Menon, Usha ; Kjaer, Susanne K. ; Levine, Douglas A. ; Gronwald, Jacek ; Culver, Hoda Anton ; Whittemore, Alice S. ; Karlan, Beth Y. ; Lambrechts, Diether ; Wentzensen, Nicolas ; Kupryjanczyk, Jolanta ; Chang-Claude, Jenny ; Bandera, Elisa V. ; Hogdall, Estrid ; Heitz, Florian ; Kaye, Stanley B. ; Fasching, Peter A. ; Campbell, Ian ; Goodman, Marc T. ; Pejovic, Tanja ; Bean, Yukie T. ; Hays, Laura E. ; Lurie, Galina ; Eccles, Diana ; Hein, Alexander ; Beckmann, Matthias W. ; Ekici, Arif B. ; Paul, James ; Brown, Robert ; Flanagan, James M. ; Harter, Philipp ; Du Bois, Andreas ; Schwaab, Ira ; Hogdall, Claus K. ; Lundvall, Lene ; Olson, Sara H. ; Orlow, Irene ; Paddock, Lisa E. ; Rudolph, Anja ; Eilber, Ursula ; Dansonka-Mieszkowska, Agnieszka ; Rzepecka, Iwona K. ; Ziolkowska-Seta, Izabela ; Brinton, Louise A. ; Yang, Hannah ; Garcia-Closas, Montserrat ; Despierre, Evelyn ; Lambrechts, Sandrina ; Vergote, Ignace ; Walsh, Christine S. ; Lester, Jenny ; Sieh, Weiva ; McGuire, Valerie ; Rothstein, Joseph H. ; Ziogas, Argyrios ; Lubinski, Jan ; Cybulski, Cezary ; Menkiszak, Janusz ; Jensen, Allan ; Gayther, Simon A. ; Ramus, Susan J. ; Gentry-Maharaj, Aleksandra ; Berchuck, Andrew ; Wu, Anna H. ; Pike, Malcolm C. ; Van Den Berg, David ; Terry, Kathryn L. ; Vitonis, Allison F. ; Ramirez, Starr M. ; Rider, David N. ; Knutson, Keith L ; Sellers, Thomas A. ; Phelan, Catherine M. ; Doherty, Jennifer A. ; Johnatty, Sharon E. ; De Fazio, Anna ; Song, Honglin ; Tyrer, Jonathan ; Kalli, Kimberly R. ; Fridley, Brooke L. ; Cunningham, Julie M ; Goode, Ellen L. / Variation in NF-κB signaling pathways and survival in invasive epithelial ovarian cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2014 ; Vol. 23, No. 7. pp. 1421-1427.
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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.",
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TY - JOUR

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 - Chenevix-Trench, Georgia

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 - Dansonka-Mieszkowska, Agnieszka

AU - Rzepecka, Iwona K.

AU - Ziolkowska-Seta, Izabela

AU - Brinton, Louise A.

AU - Yang, Hannah

AU - Garcia-Closas, Montserrat

AU - Despierre, Evelyn

AU - Lambrechts, Sandrina

AU - Vergote, Ignace

AU - Walsh, Christine S.

AU - Lester, Jenny

AU - Sieh, Weiva

AU - McGuire, Valerie

AU - Rothstein, Joseph H.

AU - Ziogas, Argyrios

AU - Lubinski, Jan

AU - Cybulski, Cezary

AU - Menkiszak, Janusz

AU - Jensen, Allan

AU - Gayther, Simon A.

AU - Ramus, Susan J.

AU - Gentry-Maharaj, Aleksandra

AU - Berchuck, Andrew

AU - Wu, Anna H.

AU - Pike, Malcolm C.

AU - Van Den Berg, David

AU - Terry, Kathryn L.

AU - Vitonis, Allison F.

AU - Ramirez, Starr M.

AU - Rider, David N.

AU - Knutson, Keith L

AU - Sellers, Thomas A.

AU - Phelan, Catherine M.

AU - Doherty, Jennifer A.

AU - Johnatty, Sharon E.

AU - De Fazio, Anna

AU - Song, Honglin

AU - Tyrer, Jonathan

AU - Kalli, Kimberly R.

AU - Fridley, Brooke L.

AU - Cunningham, Julie M

AU - Goode, Ellen L

PY - 2014

Y1 - 2014

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.

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

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

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AN - SCOPUS:84903985077

VL - 23

SP - 1421

EP - 1427

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

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