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

Cell Rep Med. 2022 Mar 15;3(3):100542. doi: 10.1016/j.xcrm.2022.100542.


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.

Keywords: Mendelian randomization; endometriosis; epithelial ovarian cancer; genetic association; genetic correlation; genetic risk; histotype; meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Ovarian Epithelial / genetics
  • Endometriosis* / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Neoplasms, Glandular and Epithelial* / complications
  • Ovarian Neoplasms* / genetics