Yao Xinrui, Dong Sitong, Li Xiao, Liu Ouxuan, Hu Yuexin, Wang Yuxuan, Fan Xiangcheng, Lin Bei
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, China.
Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang, China.
Int J Med Sci. 2025 Jun 23;22(12):3142-3153. doi: 10.7150/ijms.112922. eCollection 2025.
Several relevant reports have shown that changes in the composition of the gut microbiota are related to the pathogenesis of endometrial cancer (EC). However, the causal effect of the gut microbiota on EC remains unknown. A two-sample Mendelian randomization (MR) study was used to assess the causal effects of the gut microbiota on EC, EC with endometrioid histologies and EC with non-endometrioid histologies. The genetic statistics of the gut microbiota, including 18,340 participants, were acquired from the MiBioGen database. The summary statistics of EC, EC with endometrioid histologies and EC with non-endometrioid histologies were obtained from the publicly available Genome-wide Association Study (GWAS) database. Suitable single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) ( < 5×10, r < 0.001). The causal effects were evaluated via the MR-Egger regression method, the inverse-variance weighted (IVW) method, the weighted median test, the weighted mode test, and the simple mode test. The IVW analysis suggested that (OR=0.82, 95%CI=0.78-0.85, =1.29×10), (OR=0.90, 95%CI=0.87-0.94, =3.78×10), and (OR=0.92, 95%CI=0.87-0.98, =0.01) had protective effects on EC and its subtypes. (OR=1.29, 95%CI=1.19-1.39, =2.32×10) served as a risk factor for EC, and (OR=1.33, 95%CI=1.10-1.62, =3.68×10) had detrimental effects on EC with non-endometrioid histologies. The causal relationship between the gut microbiota and EC was explored through two-sample MR analysis, which is helpful for further understanding the gut microbiota-mediated development mechanism underlying EC.
多项相关报告表明，肠道微生物群组成的变化与子宫内膜癌（EC）的发病机制有关。然而，肠道微生物群对EC的因果效应仍不清楚。本研究采用两样本孟德尔随机化（MR）方法，评估肠道微生物群对EC、子宫内膜样组织学类型的EC和非子宫内膜样组织学类型的EC的因果效应。肠道微生物群的遗传统计数据（包括18340名参与者）来自MiBioGen数据库。EC、子宫内膜样组织学类型的EC和非子宫内膜样组织学类型的EC的汇总统计数据来自公开可用的全基因组关联研究（GWAS）数据库。选择合适的单核苷酸多态性（SNP）作为工具变量（IVs）（<5×10，r<0.001）。通过MR-Egger回归法、逆方差加权（IVW）法、加权中位数检验、加权模式检验和简单模式检验评估因果效应。IVW分析表明，（比值比=0.82，95%置信区间=0.78-0.85，=1.29×10）、（比值比=0.90，95%置信区间=0.87-0.94，=3.78×10）和（比值比=0.92，95%置信区间=0.87-0.98，=0.01）对EC及其亚型具有保护作用。（比值比=1.29，95%置信区间=1.19-1.39，=2.32×10）是EC的一个危险因素，（比值比=1.33，95%置信区间=1.10-1.62，=3.68×10）对非子宫内膜样组织学类型的EC有不利影响。通过两样本MR分析探讨了肠道微生物群与EC之间的因果关系，这有助于进一步了解肠道微生物群介导的EC潜在发展机制。
