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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; Hodgson, S; Jones, A; Martin, NG; Gordon, S; et al. Painter, JN; O'Mara, TA; Morris, AP; Cheng, THT; Gorman, M; Martin, L; Hodgson, S; Jones, A; Martin, NG; Gordon, S; Henders, AK; Attia, J; McEvoy, M; Holliday, EG; Scott, RJ; Webb, PM; Fasching, PA; Beckmann, MW; Ekici, AB; Hein, A; Rübner, M; Hall, P; Czene, K; Dörk, T; Dürst, 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) Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses. Cancer Med, 7 (5). pp. 1978-1987. ISSN 2045-7634 https://doi.org/10.1002/cam4.1445
SGUL Authors: Hodgson, Shirley Victoria

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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.

Item Type: Article
Additional Information: © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Cross-disease analysis, endometrial cancer, endometriosis, genetic correlation, genome-wide association study
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: Cancer Med
ISSN: 2045-7634
Language: eng
Dates:
DateEvent
9 May 2018Published
2 April 2018Published Online
21 January 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
UM1 CA164920National Cancer Institutehttp://dx.doi.org/10.13039/100000054
R01 CA128978National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
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U19 CA148112NCI NIH HHSUNSPECIFIED
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339435National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
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1031333National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
223175Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
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C5047/A15007Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C5047/A10692Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C8197/A16565Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
W81XWH-10-1-03U.S. Department of Defensehttp://dx.doi.org/10.13039/100000005
20110222Karolinska Institutethttp://dx.doi.org/10.13039/501100004047
20110483Karolinska Institutethttp://dx.doi.org/10.13039/501100004047
20110141Karolinska Institutethttp://dx.doi.org/10.13039/501100004047
DF 07015Karolinska Institutethttp://dx.doi.org/10.13039/501100004047
11 0439Swedish Cancer SocietyUNSPECIFIED
C1287/A10118Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C1287/A12014Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
PPD/RPCI.07Ovarian Cancer Research Fundhttp://dx.doi.org/10.13039/100001282
DAMD17-01-1-0729Medical Research and Materiel Command, U.S. Army Medical Departmenthttp://dx.doi.org/10.13039/100000182
ID400413National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
ID400281National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
PubMed ID: 29608257
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109875
Publisher's version: https://doi.org/10.1002/cam4.1445

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