Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium

Journal article


Publication Details

Author(s): Johnatty SE, Tyrer JP, Kar S, Beesley J, Lu Y, Gao B, Fasching P, Hein A, Ekici AB, Beckmann M, Lambrechts D, Van Nieuwenhuysen E, Vergote I, Lambrechts S, Rossing MA, Doherty JA, Chang-Claude J, Modugno F, Ness RB, Moysich KB, Levine DA, Kiemeney LA, Massuger LFAG, Gronwald J, Lubinski J, Jakubowska A, Cybulski C, Brinton L, Lissowska J, Wentzensen N, Song H, Rhenius V, Campbell I, Eccles D, Sieh W, Whittemore AS, Mcguire V, Rothstein JH, Sutphen R, Anton-Culver H, Ziogas A, Gayther SA, Gentry-Maharaj A, Menon U, Ramus SJ, Pearce CL, Pike MC, Stram DO, Wu AH, Kupryjanczyk J, Dansonka-Mieszkowska A, Rzepecka IK, Spiewankiewicz B, Goodman MT, Wilkens LR, Carney ME, Thompson PJ, Heitz F, Du Bois A, Schwaab I, Harter P, Pisterer J, Hillemanns P, Karlan BY, Walsh C, Lester J, Orsulic S, Winham SJ, Earp M, Larson MC, Fogarty ZC, Hogdall E, Jensen A, Kjaer SK, Fridley BL, Cunningham JM, Vierkant RA, Schildkraut JM, Iversen ES, Terry KL, Cramer DW, Bandera EV, Orlow I, Pejovic T, Bean Y, Hogdall C, Lundvall L, Mcneish I, Paul J, Carty K, Siddiqui N, Glasspool R, Sellers T, Kennedy C, Chiew YE, Berchuck A, Macgregor S, Pharoah PDP, Goode EL, Defazio A, Webb PM, Chenevix-Trench G
Journal: Clinical Cancer Research
Publication year: 2015
Volume: 21
Journal issue: 23
Pages range: 5264-76
ISSN: 1078-0432


Abstract


Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome.We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with >=4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis.Five SNPs were significantly associated (P <= 1.0 × 10(-5)) with poorer outcomes in at least one of the four analyses, three of which, rs4910232 (11p15.3), rs2549714 (16q23), and rs6674079 (1q22), were located in long noncoding RNAs (lncRNAs) RP11-179A10.1, RP11-314O13.1, and RP11-284F21.8, respectively (P <= 7.1 × 10(-6)). ENCODE ChIP-seq data at 1q22 for normal ovary show evidence of histone modification around RP11-284F21.8, and rs6674079 is perfectly correlated with another SNP within the super-enhancer MEF2D, expression levels of which were reportedly associated with prognosis in another solid tumor. YAP1- and WWTR1 (TAZ)-stimulated gene expression and high-density lipoprotein (HDL)-mediated lipid transport pathways were associated with PFS and OS, respectively, in the cohort who had standard chemotherapy (pGSEA <=6 × 10(-3)).We have identified SNPs in three lncRNAs that might be important targets for novel EOC therapies. Clin Cancer Res; 21(23); 5264-76. ©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

Beatson West of Scotland Cancer Centre (BWSCC)
Brigham and Women's Hospital (BWH)
Cedars-Sinai Medical Center
Danish Cancer Society
Dartmouth College
Deutsches Krebsforschungszentrum (DKFZ)
Duke University
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Fred Hutchinson Cancer Research Center
Glasgow Royal Infirmary (GRI)
Institute for Oncology Ljubljana (OIL)
Institut für Humangenetik Wiesbaden
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Kliniken Essen-Mitte
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
Oregon Health and Science University (OSHU)
Peter MacCallum Cancer Centre
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Radboud University Nijmegen
Roswell Park Cancer Institute
Stanford University
The State University of New Jersey (Rutgers)
University College London (UCL)
University of California Irvine
University of Cambridge
University of Copenhagen
University of Glasgow
University of Hawaii (U.H.)
University of Kansas (KU)
University of Pittsburgh
University of Southampton
University of Southern California (USC)
University of South Florida (USF)
University of Texas Health Science Center at Houston (UTHealth)
Westmead Hospital


How to cite

APA:
Johnatty, S.E., Tyrer, J.P., Kar, S., Beesley, J., Lu, Y., Gao, B.,... Chenevix-Trench, G. (2015). Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium. Clinical Cancer Research, 21(23), 5264-76. https://dx.doi.org/10.1158/1078-0432.CCR-15-0632

MLA:
Johnatty, Sharon E., et al. "Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium." Clinical Cancer Research 21.23 (2015): 5264-76.

BibTeX: 

Last updated on 2019-21-07 at 07:53