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

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 P, 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 (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 7

Pages Range: 1978-1987

Journal Issue: 5

DOI: 10.1002/cam4.1445

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.

Authors with CRIS profile

Involved external institutions

QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) University of Oxford United Kingdom (GB) St George's, University of London (SGUL) / St George's Hospital Medical School United Kingdom (GB) University of Queensland Australia (AU) John Hunter Hospital Australia (AU) University of Newcastle (UoN) Australia (AU) Karolinska Institute Sweden (SE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Friedrich-Schiller-Universität Jena Germany (DE) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) Mayo Clinic United States (USA) (US) University of Bergen / Universitetet i Bergen Norway (NO) University of Cambridge United Kingdom (GB) University of Sheffield United Kingdom (GB) The University of Melbourne Australia (AU) London School of Hygiene and Tropical Medicine United Kingdom (GB) The Institute of Cancer Research (ICR) United Kingdom (GB) Ruprecht-Karls-Universität Heidelberg Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Technische Universität München (TUM) Germany (DE) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO)

How to cite

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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