Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Cuellar-Partida G, Lu Y, Dixon SC, Fasching PA, Hein A, Burghaus S, Beckmann M, Lambrechts D, Van Nieuwenhuysen E, Vergote I, Vanderstichele A, Doherty JA, Rossing MA, Chang-Claude J, Rudolph A, Wang-Gohrke S, Goodman MT, Bogdanova N, Doerk T, Duerst M, Hillemanns P, Runnebaum IB, Antonenkova N, Butzow R, Leminen A, Nevanlinna H, Pelttari LM, Edwards RP, Kelley JL, Modugno F, Moysich KB, Ness RB, Cannioto R, Hogdall E, Hogdall C, Jensen A, Giles GG, Bruinsma F, Kjaer SK, Hildebrandt MAT, Liang D, Lu KH, Wu X, Bisogna M, Dao F, Levine DA, Cramer DW, Terry KL, Tworoger SS, Stampfer M, Missmer S, Bjorge L, Salvesen HB, Kopperud RK, Bischof K, Aben KKH, Kiemeney LA, Massuger LFAG, Brooks-Wilson A, Olson SH, Mcguire V, Rothstein JH, Sieh W, Whittemore AS, Cook LS, Le ND, Gilks CB, Gronwald J, Jakubowska A, Lubinski J, Kluz T, Song H, Tyrer JP, Wentzensen N, Brinton L, Trabert B, Lissowska J, Mclaughlin JR, Narod SA, Phelan C, Anton-Culver H, Ziogas A, Eccles D, Campbell I, Gayther SA, Gentry-Maharaj A, Menon U, Ramus SJ, Wu AH, Dansonka-Mieszkowska A, Kupryjanczyk J, Timorek A, Szafron L, Cunningham JM, Fridley BL, Winham SJ, Bandera EV, Poole EM, Morgan TK, Goode EL, Schildkraut JM, Pearce CL, Berchuck A, Pharoah PDP, Webb PM, Chenevix-Trench G, Risch HA, Macgregor S
Zeitschrift: Human genetics
Jahr der Veröffentlichung: 2016
Band: 135
Heftnummer: 7
Seitenbereich: 741-56
ISSN: 0340-6717
eISSN: 1432-1203


Abstract

Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Burghaus, Stefanie Dr. med.
Frauenklinik
Hein, Alexander PD Dr.
Frauenklinik


Einrichtungen weiterer Autorinnen und Autoren

Brigham and Women's Hospital (BWH)
British Columbia Cancer Agency
Cancer Council Victoria
Cedars-Sinai Medical Center
Danish Cancer Society Research Center
Dartmouth College
Deutsches Krebsforschungszentrum (DKFZ)
Duke University
Friedrich-Schiller-Universität Jena
Harvard University
Haukeland University Hospital / Haukeland universitetssykehus
Helsingin yliopisto / University of Helsinki
Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS)
H. Lee Moffitt Cancer Center & Research Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
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
Monash University
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)
Public Health Ontario
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Radboud University Nijmegen
Roswell Park Cancer Institute
Rutgers Cancer Institute of New Jersey
Stanford University
Texas Southern University (TSU)
Universität Ulm
University College London (UCL)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of British Columbia
University of California Irvine
University of California Los Angeles (UCLA)
University of Cambridge
University of Copenhagen
University of Kansas (KU)
University of New Mexico
University of Pittsburgh
University of Southampton
University of Southern California (USC)
University of Texas MD Anderson Cancer Center
University of Toronto
University of Virginia (UVA)
University of Washington
Uniwersytet Rzeszowski
Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu


Zitierweisen

APA:
Cuellar-Partida, G., Lu, Y., Dixon, S.C., Fasching, P.A., Hein, A., Burghaus, S.,... Macgregor, S. (2016). Assessing the genetic architecture of epithelial ovarian cancer histological subtypes. Human genetics, 135(7), 741-56. https://dx.doi.org/10.1007/s00439-016-1663-9

MLA:
Cuellar-Partida, Gabriel, et al. "Assessing the genetic architecture of epithelial ovarian cancer histological subtypes." Human genetics 135.7 (2016): 741-56.

BibTeX: 

Zuletzt aktualisiert 2018-10-11 um 02:08