Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses

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Details zur Publikation

Autor(en): Painter JN, O'Mara TA, Morris AP, Cheng THT, Gorman M, Martin L, Hodson S, Jones A, Martin NG, Gordon S, Henders AK, Attia J, Mcevoy M, Holliday EG, Scott RJ, Webb PM, Fasching PA, Beckmann M, Ekici AB, Hein A, Rübner M, Hall P, Czene K, Doerk T, Duerst M, Hillemanns P, Runnebaum I, Lambrechts D, Amant F, Annibali D, Depreeuw J, Vanderstichele A, Goode EL, Cunningham JM, Dowdy SC, Winham SJ, Trovik J, Hoivik E, Werner HMJ, Krakstad C, Ashton K, Otton G, Proietto T, Tham E, Mints M, Ahmed S, Healey CS, Shah M, Pharoah PDP, Dunning AM, Dennis J, Bolla MK, Michailidou K, Wang Q, Tyrer JP, Hopper JL, Peto J, Swerdlow AJ, Burwinkel B, Brenner H, Meindl A, Brauch H, Lindblom A, Chang-Claude J, Couch FJ, Giles GG, Kristensen VN, Cox A, Zondervan KT, Nyholt DR, Macgregor S, Montgomery GW, Tomlinson I, Easton DF, Thompson DJ, Spurdle AB
Zeitschrift: Cancer Medicine
Jahr der Veröffentlichung: 2018
Band: 7
Heftnummer: 5
Seitenbereich: 1978-1987
ISSN: 2045-7634


Abstract

Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg  = 0.23, P = 9.3 × 10-3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10-3 ) and concordance in effect direction (P = 2.0 × 10-3 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10-5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10-8 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.


FAU-Autoren / FAU-Herausgeber

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
Rübner, Matthias PD Dr.
Frauenklinik


Autor(en) der externen Einrichtung(en)
Deutsches Krebsforschungszentrum (DKFZ)
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Friedrich-Schiller-Universität Jena
Hannover Medical School / Medizinische Hochschule Hannover (MHH)
John Hunter Hospital
Karolinska Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
London School of Hygiene and Tropical Medicine
Mayo Clinic
Oslo University Hospital / Oslo Universitetssykehus
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Ruprecht-Karls-Universität Heidelberg
St George's, University of London (SGUL) / St George's Hospital Medical School
Technische Universität München (TUM)
The Institute of Cancer Research (ICR)
The University of Melbourne
University of Bergen
University of Cambridge
University of Newcastle (UoN)
University of Oxford
University of Queensland
University of Sheffield


Zitierweisen

APA:
Painter, J.N., O'Mara, T.A., Morris, A.P., Cheng, T.H.T., Gorman, M., Martin, L.,... Spurdle, A.B. (2018). Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses. Cancer Medicine, 7(5), 1978-1987. https://dx.doi.org/10.1002/cam4.1445

MLA:
Painter, Jodie N., et al. "Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses." Cancer Medicine 7.5 (2018): 1978-1987.

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Zuletzt aktualisiert 2018-01-11 um 21:08