Risk of Ovarian Cancer and the NF-?B Pathway: Genetic Association with IL1A and TNFSF10

Charbonneau B, Block MS, Bamlet WR, Vierkant RA, Kalli KR, Fogarty Z, Rider DN, Sellers TA, Tworoger SS, Poole E, Risch HA, Salvesen HB, Kiemeney LA, Baglietto L, Giles GG, Severi G, Trabert B, Wentzensen N, Chenevix-Trench G, Whittemore AS, Sieh W, Chang-Claude J, Bandera EV, Orlow I, Terry K, Goodman MT, Thompson PJ, Cook LS, Rossing MA, Ness RB, Narod SA, Kupryjanczyk J, Lu K, Butzow R, Doerk T, Pejovic T, Campbell I, Le ND, Bunker CH, Bogdanova N, Runnebaum IB, Eccles D, Paul J, Wu AH, Gayther SA, Hogdall E, Heitz F, Kaye SB, Karlan BY, Anton-Culver H, Gronwald J, Hogdall CK, Lambrechts D, Fasching P, Menon U, Schildkraut J, Pearce CL, Levine DA, Kjaer SK, Cramer D, Flanagan JM, Phelan CM, Brown R, Massuger LFAG, Song H, Doherty JA, Krakstad C, Liang D, Odunsi K, Berchuck A, Jensen A, Lubinski J, Nevanlinna H, Bean YT, Lurie G, Ziogas A, Walsh C, Despierre E, Brinton L, Hein A, Rudolph A, Dansonka-Mieszkowska A, Olson SH, Harter P, Tyrer J, Vitonis AF, Brooks-Wilson A, Aben KK, Pike MC, Ramus SJ, Wik E, Cybulski C, Lin J, Sucheston L, Edwards R, Mcguire V, Lester J, Du Bois A, Lundvall L, Wang-Gohrke S, Szafron LM, Lambrechts S, Yang H, Beckmann M, Pelttari LM, Van Altena AM, Van Den Berg D, Halle MK, Gentry-Maharaj A, Schwaab I, Chandran U, Menkiszak J, Ekici AB, Wilkens LR, Leminen A, Modugno F, Friel G, Rothstein JH, Vergote I, Garcia-Closas M, Hildebrandt MAT, Sobiczewski P, Kelemen LE, Pharoah PDP, Moysich K, Knutson KL, Cunningham JM, Fridley BL, Goode EL (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Publisher: American Association for Cancer Research

Book Volume: 74

Pages Range: 852-61

Journal Issue: 3

DOI: 10.1158/0008-5472.CAN-13-1051

Abstract

A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1? (IL1A) is both regulated by and able to activate NF-?B, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-?B 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, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (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 < 2.5 × 10(-5), only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential 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. Cancer Res; 74(3); 852-61. ©2013 AACR.

Authors with CRIS profile

Involved external institutions

University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Mayo Clinic United States (USA) (US) University of South Florida (USF) United States (USA) (US) Harvard University United States (USA) (US) HELIOS Kliniken Germany (DE) Rigshospitalet Denmark (DK) University of Bergen / Universitetet i Bergen Norway (NO) Cancer Council Victoria Australia (AU) Stanford University United States (USA) (US) National Cancer Institute (NCI) United States (USA) (US) University of Medicine and Dentistry of New Jersey (UMDNJ) United States (USA) (US) University of Toronto Canada (CA) Cedars-Sinai Medical Center United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) University of Texas MD Anderson Cancer Center United States (USA) (US) The University of Melbourne Australia (AU) University of Pittsburgh United States (USA) (US) University of Southampton United Kingdom (GB) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) University of Southern California (USC) United States (USA) (US) University of California Irvine United States (USA) (US) International Hereditary Cancer Center Poland (PL) Duke University United States (USA) (US) Danish Cancer Society Denmark (DK) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB) Oregon Health and Science University (OSHU) United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) Radboud University Nijmegen Netherlands (NL) Helsingin yliopisto / University of Helsinki Finland (FI) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University of Cambridge United Kingdom (GB) Texas Southern University (TSU) United States (USA) (US) Friedrich-Schiller-Universität Jena Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Roswell Park Cancer Institute United States (USA) (US) Institut für Humangenetik Wiesbaden Germany (DE) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Alberta Health Services (AHS) Canada (CA) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) University College London (UCL) United Kingdom (GB) Yale University United States (USA) (US) British Columbia Cancer Agency Canada (CA) University of New Mexico (UNM) / Universidad de Nuevo México United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) University of Kansas (KU) United States (USA) (US) Fred Hutchinson Cancer Research Center Canada (CA) Dartmouth College United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Universität Ulm Germany (DE)

How to cite

APA:

Charbonneau, B., Block, M.S., Bamlet, W.R., Vierkant, R.A., Kalli, K.R., Fogarty, Z.,... Goode, E.L. (2014). Risk of Ovarian Cancer and the NF-?B Pathway: Genetic Association with IL1A and TNFSF10. Cancer Research, 74(3), 852-61. https://dx.doi.org/10.1158/0008-5472.CAN-13-1051

MLA:

Charbonneau, Bridget, et al. "Risk of Ovarian Cancer and the NF-?B Pathway: Genetic Association with IL1A and TNFSF10." Cancer Research 74.3 (2014): 852-61.

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