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A multi-level investigation of the genetic relationship between endometriosis and ovarian cancer histotypes.
Mortlock, Sally; Corona, Rosario I; Kho, Pik Fang; Pharoah, Paul; Seo, Ji-Heui; Freedman, Matthew L; Gayther, Simon A; Siedhoff, Matthew T; Rogers, Peter A W; Leuchter, Ronald; Walsh, Christine S; Cass, Ilana; Karlan, Beth Y; Rimel, B J; Montgomery, Grant W; Lawrenson, Kate; Kar, Siddhartha P.
Affiliation
  • Mortlock S; The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
  • Corona RI; Women's Cancer Research Program at Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Kho PF; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Pharoah P; School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia.
  • Seo JH; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN Cambridge, UK.
  • Freedman ML; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, CB1 8RN Cambridge, UK.
  • Gayther SA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Siedhoff MT; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Rogers PAW; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Leuchter R; Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Walsh CS; Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Cass I; University of Melbourne Department of Obstetrics and Gynaecology, and Gynaecology Research Centre, Royal Women's Hospital, Parkville, VIC 3052, Australia.
  • Karlan BY; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Rimel BJ; Department of Obstetrics and Gynecology, University of Colorado, Aurora, CO, USA.
  • Montgomery GW; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • Lawrenson K; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Cell Rep Med ; 3(3): 100542, 2022 03 15.
Article in En | MEDLINE | ID: mdl-35492879
ABSTRACT
Endometriosis 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ovarian Neoplasms / Neoplasms, Glandular and Epithelial / Endometriosis Type of study: Clinical_trials / Systematic_reviews Limits: Female / Humans Language: En Journal: Cell Rep Med Year: 2022 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ovarian Neoplasms / Neoplasms, Glandular and Epithelial / Endometriosis Type of study: Clinical_trials / Systematic_reviews Limits: Female / Humans Language: En Journal: Cell Rep Med Year: 2022 Document type: Article Affiliation country: