Inherited variants affecting RNA editing may contribute to ovarian cancer susceptibility: results from a large-scale collaboration

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Permuth JB, Reid B, Earp M, Chen YA, Monteiro ANA, Chen Z, Chenevix-Trench G, Fasching P, Beckmann M, Lambrechts D, Vanderstichele A, Van Niewenhuyse E, Vergote I, Rossing MA, Doherty JA, Chang-Claude J, Moysich K, Odunsi K, Goodman MT, Shvetsov YB, Wilkens LR, Thompson PJ, Doerk T, Bogdanova N, Butzow R, Nevanlinna H, Pelttari L, Leminen A, Modugno F, Edwards RP, Ness RB, Kelley J, Heitz F, Karlan B, Lester J, Kjaer SK, Jensen A, Giles G, Hildebrandt M, Liang D, Lu KH, Wu X, Levine DA, Bisogna M, Berchuck A, Cramer DW, Terry KL, Tworoger SS, Poole EM, Bandera EV, Fridley B, Cunningham J, Winham SJ, Olson SH, Orlow I, Bjorge L, Kiemeney LA, Massuger L, Pejovic T, Moffitt M, Le N, Cook LS, Brooks-Wilson A, Kelemen LE, Gronwald J, Lubinski J, Wentzensen N, Brinton LA, Lissowska J, Yang H, Hogdall E, Hogdall C, Lundvall L, Pharoah PDP, Song H, Campbell I, Eccles D, Mcneish I, Whittemore A, Mcguire V, Sieh W, Rothstein J, Phelan CM, Risch H, Narod S, Mclaughlin J, Anton-Culver H, Ziogas A, Menon U, Gayther S, Ramus SJ, Gentry-Maharaj A, Pearce CL, Wu AH, Kupryjanczyk J, Dansonka-Mieszkowska A, Schildkraut JM, Cheng JQ, Goode EL, Sellers TA
Zeitschrift: Oncotarget
Jahr der Veröffentlichung: 2016
Band: 7
Heftnummer: 45
Seitenbereich: 72381-72394
ISSN: 1949-2553


Abstract

RNA editing in mammals is a form of post-transcriptional modification in which adenosine is converted to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes. Based on evidence of altered ADAR expression in epithelial ovarian cancers (EOC), we hypothesized that single nucleotide polymorphisms (SNPs) in ADAR genes modify EOC susceptibility, potentially by altering ovarian tissue gene expression. Using directly genotyped and imputed data from 10,891 invasive EOC cases and 21,693 controls, we evaluated the associations of 5,303 SNPs in ADAD1, ADAR, ADAR2, ADAR3, and SND1. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), with adjustment for European ancestry. We conducted gene-level analyses using the Admixture Maximum Likelihood (AML) test and the Sequence-Kernel Association test for common and rare variants (SKAT-CR). Association analysis revealed top risk-associated SNP rs77027562 (OR (95% CI)= 1.39 (1.17-1.64), P=1.0x10-4) in ADAR3 and rs185455523 in SND1 (OR (95% CI)= 0.68 (0.56-0.83), P=2.0x10-4). When restricting to serous histology (n=6,500), the magnitude of association strengthened for rs185455523 (OR=0.60, P=1.0x10-4). Gene-level analyses revealed that variation in ADAR was associated (P<0.05) with EOC susceptibility, with PAML=0.022 and PSKAT-CR=0.020. Expression quantitative trait locus analysis in EOC tissue revealed significant associations (P<0.05) with ADAR expression for several SNPs in ADAR, including rs1127313 (G/A), a SNP in the 3' untranslated region. In summary, germline variation involving RNA editing genes may influence EOC susceptibility, warranting further investigation of inherited and acquired alterations affecting RNA editing.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


Einrichtungen weiterer Autorinnen und Autoren

Brigham and Women's Hospital (BWH)
British Columbia Cancer Agency
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
Harvard University
Helsingin yliopisto / University of Helsinki
H. Lee Moffitt Cancer Center & Research Institute
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
National Cancer Institute (NCI)
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
Rigshospitalet
Roswell Park Cancer Institute
Rutgers Cancer Institute of New Jersey
Stanford University
Texas Southern University (TSU)
The University of Melbourne
University College London (UCL)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Bergen
University of California Irvine
University of Cambridge
University of Glasgow
University of Hawaii (U.H.)
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


Zitierweisen

APA:
Permuth, J.B., Reid, B., Earp, M., Chen, Y.A., Monteiro, A.N.A., Chen, Z.,... Sellers, T.A. (2016). Inherited variants affecting RNA editing may contribute to ovarian cancer susceptibility: results from a large-scale collaboration. Oncotarget, 7(45), 72381-72394. https://dx.doi.org/10.18632/oncotarget.10546

MLA:
Permuth, Jennifer B., et al. "Inherited variants affecting RNA editing may contribute to ovarian cancer susceptibility: results from a large-scale collaboration." Oncotarget 7.45 (2016): 72381-72394.

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Zuletzt aktualisiert 2019-25-04 um 15:08