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A multi-level investigation of the genetic relationship between endometriosis and ovarian cancer histotypes.

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cam.issuedOnline2022-03-15
dc.contributor.authorMortlock, Sally
dc.contributor.authorCorona, Rosario I
dc.contributor.authorKho, Pik Fang
dc.contributor.authorPharoah, Paul
dc.contributor.authorSeo, Ji-Heui
dc.contributor.authorFreedman, Matthew L
dc.contributor.authorGayther, Simon A
dc.contributor.authorSiedhoff, Matthew T
dc.contributor.authorRogers, Peter AW
dc.contributor.authorLeuchter, Ronald
dc.contributor.authorWalsh, Christine S
dc.contributor.authorCass, Ilana
dc.contributor.authorKarlan, Beth Y
dc.contributor.authorRimel, BJ
dc.contributor.authorOvarian Cancer Association Consortium, International Endometriosis Genetics Consortium
dc.contributor.authorMontgomery, Grant W
dc.contributor.authorLawrenson, Kate
dc.contributor.authorKar, Siddhartha P
dc.contributor.orcidPharoah, Paul [0000-0001-8494-732X]
dc.date.accessioned2022-06-07T08:15:46Z
dc.date.available2022-06-07T08:15:46Z
dc.date.issued2022-03-15
dc.date.updated2022-06-07T08:15:45Z
dc.description.abstractEndometriosis is associated with increased risk of epithelial ovarian cancers (EOCs). Using data from large endometriosis and EOC genome-wide association meta-analyses, we estimate the genetic correlation and evaluate the causal relationship between genetic liability to endometriosis and EOC histotypes, and identify shared susceptibility loci. We estimate a significant genetic correlation (rg) between endometriosis and clear cell (rg = 0.71), endometrioid (rg = 0.48), and high-grade serous (rg = 0.19) ovarian cancer, associations supported by Mendelian randomization analyses. Bivariate meta-analysis identified 28 loci associated with both endometriosis and EOC, including 19 with evidence for a shared underlying association signal. Differences in the shared risk suggest different underlying pathways may contribute to the relationship between endometriosis and the different histotypes. Functional annotation using transcriptomic and epigenomic profiles of relevant tissues/cells highlights several target genes. This comprehensive analysis reveals profound genetic overlap between endometriosis and EOC histotypes with valuable genomic targets for understanding the biological mechanisms linking the diseases.
dc.identifier.doi10.17863/CAM.85222
dc.identifier.eissn2666-3791
dc.identifier.issn2666-3791
dc.identifier.other35492879
dc.identifier.otherPMC9040176
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337813
dc.languageeng
dc.language.isoeng
dc.publisherElsevier BV
dc.publisher.urlhttp://dx.doi.org/10.1016/j.xcrm.2022.100542
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourcenlmid: 101766894
dc.sourceessn: 2666-3791
dc.subjectMendelian randomization
dc.subjectendometriosis
dc.subjectepithelial ovarian cancer
dc.subjectgenetic association
dc.subjectgenetic correlation
dc.subjectgenetic risk
dc.subjecthistotype
dc.subjectmeta-analysis
dc.subjectCarcinoma, Ovarian Epithelial
dc.subjectEndometriosis
dc.subjectFemale
dc.subjectGenome-Wide Association Study
dc.subjectHumans
dc.subjectNeoplasms, Glandular and Epithelial
dc.subjectOvarian Neoplasms
dc.titleA multi-level investigation of the genetic relationship between endometriosis and ovarian cancer histotypes.
dc.typeArticle
dcterms.dateAccepted2022-01-29
prism.issueIdentifier3
prism.publicationNameCell Rep Med
prism.volume3
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/j.xcrm.2022.100542

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