Title: Risk of Ovarian Cancer and the NF-κB Pathway: Genetic association with IL1A and TNFSF10
Authors: Charbonneau, Bridget ×
Block, Matthew S
Bamlet, William R
Vierkant, Robert A
Kalli, Kimberly R
Fogarty, Zachary
Rider, David N
Sellers, Thomas A
Tworoger, Shelley S
Poole, Elizabeth
Risch, Harvey A
Salvesen, Helga B
Kiemeny, Lambertus A
Baglietto, Laura
Giles, Graham G
Severi, Gianluca
Trabert, Britton
Wentzensen, Nicolas
Chenevix-Trench, Georgia
Whittemore, Alice S
Sieh, Weiva
Chang-Claude, Jenny
Bandera, Elisa V
Orlow, Irene
Terry, Kathryn
Goodman, Marc T
Thompson, Pamela J
Cook, Linda S
Rossing, Mary Anne
Ness, Roberta B
Narod, Steven A
Kupryjanczyk, Jolanta
Lu, Karen
Bützow, Ralf
Dork, Thilo
Pejovic, Tanja
Campbell, Ian
Le, Nhu D
Bunker, Clareann H
Bogdanova, Natalia
Runnebaum, Ingo B
Eccles, Diana M
Wu, Anna H
Gayther, Simon A
Hogdall, Estrid
Heitz, Florian
Kaye, Stanley B
Karlan, Beth Y
Anton-Culver, Hoda
Gronwald, Jacek
Hogdall, Claus K
Lambrechts, Diether
Fasching, Peter A
Menon, Usha
Schildkraut, Joellen
Pearce, Celeste Leigh
Levine, Douglas A
Kruger Kjær, Susanne
Cramer, Daniel
Flanagan, James M
Phelan, Catherine M
Brown, Robert
Massuger, Leon F A G
Song, Honglin
Doherty, Jennifer A
Krakstad, Camilla
Liang, Dong
Odunsi, Kunle
Berchuck, Andrew
Jensen, Allan
Lubinski, Jan
Nevanlinna, Heli
Bean, Yukie T
Lurie, Galina
Ziogas, Argyrios
Walsh, Christine
Despierre, Evelyn
Brinton, Louise
Hein, Alexander
Rudolph, Anja
Dansonka-Mieszkowska, Agnieszka
Olson, Sara H
Harter, Philipp
Tyrer, Jonathan
Vitonis, Allison F
Brooks-Wilson, Angela
Aben, Katja K H
Pike, Malcolm C
Ramus, Susan J
Wik, Elisabeth
Cybulski, Cezary
Lin, Jie
Sucheston, Lara
Edwards, Robert
McGuire, Valerie
Lester, Jenny
du Bois, Andreas
Lundvall, Lene
Wang-Gohrke, Shan
Szafron, Lukasz M
Lambrechts, Sandrina
Yang, Hannah P
Beckmann, Matthias W
Pelttari, Liisa M
van Altena, Anne M
Van Den Berg, David
Halle, Mari
Gentry-Maharaj, Aleksandra
Schwaab, Ira
Chandran, Urmila
Menkiszak, Janusz
Ekici, Arif B
Wilkens, Lynne R
Leminen, Arto
Modugno, Francesmary
Friel, Grace
Rothstein, Joseph H
Vergote, Ignace
Garcia-Closas, Montserrat
Hildebrandt, Michelle A T
Sobiczewski, Piotr
Kelemen, Linda E
Pharoah, Paul D P
Moysich, Kirsten
Knutson, Keith L
Cunningham, Julie M
Fridley, Brooke L
Goode, Ellen L #
Issue Date: 14-Feb-2014
Publisher: Waverly Press
Series Title: Cancer Research vol:74 issue:3 pages:852-61
Abstract: A missense single nucleotide polymorphism in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561), but the functional implications of this polymorphism are undefined. IL-1α is regulated by and activated by NF-κB, a transcription factor family that induces transcription of IL1A along with other pro-inflammatory genes and is an important modifier in carcinogenesis. We therefore tagged SNPs in over 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell and 1,016 low grade serous (LGS), including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium (OCAC). In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer (OR=0.84, 95% CI: 0.76-0.93; p=0.00075), which remained intact even after excluding participants in the prior study (OR=0.85, 95% CI: 0.75-0.95; p=0.006). Considering a multiple-testing-corrected significance threshold of p< 2.5x10-5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential (LMP) tumors OR=0.85, 95% CI: 0.79-0.91; p=0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation related risk factors is warranted.
ISSN: 0008-5472
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gynaecological Oncology
× corresponding author
# (joint) last author

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