Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

Journal article


Publication Details

Author(s): Kar SP, Tyrer JP, Li Q, Lawrenson K, Aben KKH, Anton-Culver H, Antonenkova N, Chenevix-Trench G, Baker H, Bandera EV, Bean YT, Beckmann M, Berchuck A, Bisogna M, Bjorge L, Bogdanova N, Brinton L, Brooks-Wilson A, Butzow R, Campbell I, Carty K, Chang-Claude J, Chen YA, Chen Z, Cook LS, Cramer D, Cunningham JM, Cybulski C, Dansonka-Mieszkowska A, Dennis J, Dicks E, Doherty JA, Doerk T, Du Bois A, Duerst M, Eccles D, Easton DF, Edwards RP, Ekici AB, Fasching P, Fridley BL, Gao YT, Gentry-Maharaj A, Giles GG, Glasspool R, Goode EL, Goodman MT, Grownwald J, Harrington P, Harter P, Hein A, Heitz F, Hildebrandt MAT, Hillemanns P, Hogdall E, Hogdall CK, Hosono S, Iversen ES, Jakubowska A, Paul J, Jensen A, Ji BT, Karlan BY, Kjaer SK, Kelemen LE, Kellar M, Kelley J, Kiemeney LA, Krakstad C, Kupryjanczyk J, Lambrechts D, Lambrechts S, Le ND, Lee AW, Lele S, Leminen A, Lester J, Levine DA, Liang D, Lissowska J, Lu K, Lubinski J, Lundvall L, Massuger L, Matsuo K, Mcguire V, Mclaughlin JR, Mcneish IA, Menon U, Modugno F, Moysich KB, Narod SA, Nedergaard L, Ness RB, Nevanlinna H, Odunsi K, Olson SH, Orlow I, Orsulic S, Weber RP, Pearce CL, Pejovic T, Pelttari LM, Permuth-Wey J, Phelan CM, Pike MC, Poole EM, Ramus SJ, Risch HA, Rosen B, Rossing MA, Rothstein JH, Rudolph A, Runnebaum IB, Rzepecka IK, Salvesen HB, Schildkraut JM, Schwaab I, Shu XO, Shvetsov YB, Siddiqui N, Sieh W, Song H, Southey MC, Sucheston-Campbell LE, Tangen IL, Teo SH, Terry KL, Thompson PJ, Timorek A, Tsai YY, Tworoger SS, Van Altena AM, Van Nieuwenhuysen E, Vergote I, Vierkant RA, Wang-Gohrke S, Walsh C, Wentzensen N, Whittemore AS, Wicklund KG, Wilkens LR, Woo YL, Wu X, Wu A, Yang H, Zheng W, Ziogas A, Sellers TA, Monteiro ANA, Freedman ML, Gayther SA, Pharoah PDP
Journal: Cancer Epidemiology Biomarkers & Prevention
Publication year: 2015
Volume: 24
Journal issue: 10
Pages range: 1574-84
ISSN: 1055-9965


Abstract

Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. Cancer Epidemiol Biomarkers Prev; 24(10); 1574-84. ©2015 AACR.


FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe
Hein, Alexander PD Dr.
Frauenklinik


External institutions with authors

Aichi Cancer Center Research Institute
Beatson West of Scotland Cancer Centre (BWSCC)
British Columbia Cancer Agency
Cancer Council Victoria
Cedars-Sinai Medical Center
Dana–Farber Cancer Institute
Danish Cancer Society
Dartmouth College
Deutsches Krebsforschungszentrum (DKFZ)
Duke University
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Fred Hutchinson Cancer Research Center
Friedrich-Schiller-Universität Jena
Glasgow Royal Infirmary (GRI)
Harvard University
Haukeland University Hospital / Haukeland universitetssykehus
Helsingin yliopisto / University of Helsinki
Institut für Humangenetik Wiesbaden
Kliniken Essen-Mitte
Kyushu University / 九州大学
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Medical University of South Carolina (MUSC)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Memorial Sloan Kettering Cancer Center
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology
Oregon Health and Science University (OSHU)
Peter MacCallum Cancer Centre
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
Princess Anne Hospital
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Radboud University Nijmegen
Ramsay Sime Darby Health Care (RSDHC)
Roswell Park Cancer Institute
Rutgers Cancer Institute of New Jersey
Shanghai Cancer Institute / 上海市肿瘤研究所
Stanford University
Texas Southern University (TSU)
The University of Melbourne
Universität Ulm
University College London (UCL)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of California Irvine
University of Cambridge
University of Copenhagen
University of Glasgow
University of Hawaii (U.H.)
University of Kansas (KU)
University of Malaya (UM) / Universiti Malaya
University of New Mexico
University of Pittsburgh
University of Southern California (USC)
University of South Florida (USF)
University of Texas MD Anderson Cancer Center
University of Toronto
Vanderbilt University
Women's College Hospital
Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu


How to cite

APA:
Kar, S.P., Tyrer, J.P., Li, Q., Lawrenson, K., Aben, K.K.H., Anton-Culver, H.,... Pharoah, P.D.P. (2015). Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk. Cancer Epidemiology Biomarkers & Prevention, 24(10), 1574-84. https://dx.doi.org/10.1158/1055-9965.EPI-14-1270

MLA:
Kar, Siddhartha P., et al. "Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk." Cancer Epidemiology Biomarkers & Prevention 24.10 (2015): 1574-84.

BibTeX: 

Last updated on 2019-21-07 at 07:52