Dang Chunxiao, Liu Mengmeng, Liu Pengfei, Liu Jinxing, Yu Xiao, Dong Yan, Zhao Junde
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.
Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, 257000, China.
Sci Rep. 2024 Dec 2;14(1):29868. doi: 10.1038/s41598-024-80747-x.
Cervical cancer, ovarian cancer, and endometrial cancer are the three most common cancers in gynecology. Understanding their respective pathology is currently incomplete. Inflammatory factors play an important role in the pathophysiology of these three cancers, but the causal relationship between inflammatory factors and these three cancers is unclear.
Based on publicly available genetic databases, relevant instrumental variables were extracted according to predefined thresholds, and causal analyses of CRP, 41 circulating inflammatory factors, and three gynecological cancers were performed, mainly using the inverse variance weighted method, while bayesian analysis was performed to improve the accuracy of the results. Finally, heterogeneity, horizontal pleiotropy test, and MR Steiger test were carried out to evaluate the reliability of the findings and the causal inference strength.
One inflammatory factor (PDGF-BB) and four inflammatory factors (CXCL9, IL-6, CXCL1, and G-CSF) were identified as significantly associated with the risk of ovarian and endometrial cancers, respectively. In comparison, cervical cancer was found to have a negative causal association with one inflammatory factor (G-CSF) and endometrial cancer with two inflammatory factors (CXCL10 and CCL11).
Our MR study suggests potential causal relationships between circulating inflammatory regulators and three gynecological cancers from a genetic perspective, which contributes to further understanding of the pathomechanisms of cervical, ovarian and endometrial cancers and highlights the potential of targeting inflammatory factors as therapeutic interventions and predictors.
宫颈癌、卵巢癌和子宫内膜癌是妇科最常见的三种癌症。目前对它们各自病理的了解尚不完整。炎症因子在这三种癌症的病理生理学中起重要作用，但炎症因子与这三种癌症之间的因果关系尚不清楚。
基于公开可用的基因数据库，根据预定义阈值提取相关工具变量，对CRP、41种循环炎症因子与三种妇科癌症进行因果分析，主要采用逆方差加权法，同时进行贝叶斯分析以提高结果的准确性。最后，进行异质性、水平多效性检验和MR Steiger检验，以评估研究结果的可靠性和因果推断强度。
分别鉴定出一种炎症因子（血小板衍生生长因子BB）和四种炎症因子（CXC趋化因子配体9、白细胞介素-6、CXC趋化因子配体1和粒细胞集落刺激因子）与卵巢癌和子宫内膜癌风险显著相关。相比之下，发现宫颈癌与一种炎症因子（粒细胞集落刺激因子）呈负因果关联，子宫内膜癌与两种炎症因子（CXC趋化因子配体10和CC趋化因子配体11）呈负因果关联。
我们的孟德尔随机化研究从基因角度提示了循环炎症调节因子与三种妇科癌症之间的潜在因果关系，这有助于进一步了解宫颈癌、卵巢癌和子宫内膜癌的发病机制，并突出了将炎症因子作为治疗干预措施和预测指标的潜力。
