The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Women's Cancer Research Program at Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
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 (r) between endometriosis and clear cell (r = 0.71), endometrioid (r = 0.48), and high-grade serous (r = 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.
子宫内膜异位症与上皮性卵巢癌（EOC）的风险增加有关。我们利用来自大型子宫内膜异位症和 EOC 全基因组关联荟萃分析的数据，估计遗传易感性与子宫内膜异位症和 EOC 组织学类型之间的遗传相关性，并评估其因果关系，确定共同的易感基因座。我们估计子宫内膜异位症与透明细胞癌（r=0.71）、子宫内膜样癌（r=0.48）和高级别浆液性癌（r=0.19）之间存在显著的遗传相关性（r），孟德尔随机化分析支持这些关联。双变量荟萃分析确定了 28 个与子宫内膜异位症和 EOC 均相关的位点，其中 19 个位点具有共同潜在关联信号的证据。共同风险的差异表明，不同的潜在途径可能有助于子宫内膜异位症与不同组织学类型之间的关系。使用相关组织/细胞的转录组和表观基因组谱进行功能注释，突出了几个靶基因。这项全面的分析揭示了子宫内膜异位症和 EOC 组织学类型之间存在深刻的遗传重叠，并为理解疾病之间的生物学机制提供了有价值的基因组靶点。
