Wan An, Zhao Wei-Dong, Tao Jin-Hui
Department of Rheumatology and Immunology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Front Oncol. 2022 Oct 3;12:930243. doi: 10.3389/fonc.2022.930243. eCollection 2022.
Systemic lupus erythematosus (SLE) has been observationally associated with endometrial cancer, but the causality remains unclear. Here, we investigated for the first time the causal links between SLE and endometrial cancer risk.
Univariable and multivariable Mendelian randomization (MR) analyses were conducted to disentangle the causality of SLE with endometrial cancer. Apart from the inverse-variance weighted (IVW) method as the primary MR estimate, three complementary MR techniques including weighted median, weighted mode, and MR-Egger regression in univariable MR were conducted to clarify the robustness of the causal estimate and mediation effects of the body mass index (BMI) and were investigated within multivariable MR-IVW and MR-Egger analyses.
All univariable MR analyses consistently suggested that SLE has a protective effect on the risk of overall endometrial cancer (IVW: OR = 0.956, 95% CI = 0.932-0.981, = 0.001) and endometrioid endometrial cancer (IVW: OR = 0.965, 95% CI = 0.933-0.999, = 0.043). More compelling, after adjustment for BMI within the multivariable MR setting, the association between SLE and decreased risk of overall endometrial cancer was significantly stronger (IVW: OR = 0.952, 95% CI = 0.931-0.973, = 9.58E-06).
Our findings provide evidence of a significant causal relationship between SLE and decreased endometrial cancer risk. Further understanding of the underlying mechanisms linking SLE with endometrial cancer is therefore needed.
系统性红斑狼疮（SLE）在观察性研究中与子宫内膜癌相关，但因果关系仍不明确。在此，我们首次研究了SLE与子宫内膜癌风险之间的因果联系。
进行单变量和多变量孟德尔随机化（MR）分析，以阐明SLE与子宫内膜癌之间的因果关系。除了将逆方差加权（IVW）方法作为主要的MR估计外，在单变量MR中还进行了三种补充性MR技术，包括加权中位数、加权众数和MR-Egger回归，以阐明因果估计的稳健性以及体重指数（BMI）的中介作用，并在多变量MR-IVW和MR-Egger分析中进行了研究。
所有单变量MR分析均一致表明，SLE对总体子宫内膜癌风险具有保护作用（IVW：OR = 0.956，95% CI = 0.932 - 0.981，P = 0.001）和子宫内膜样子宫内膜癌（IVW：OR = 0.965，95% CI = 0.933 - 0.999，P = 0.043）。更有说服力的是，在多变量MR设置中对BMI进行调整后，SLE与总体子宫内膜癌风险降低之间的关联显著增强（IVW：OR = 0.952，95% CI = 0.931 - 0.973，P = 9.58E - 06）。
我们的研究结果提供了SLE与子宫内膜癌风险降低之间存在显著因果关系的证据。因此，需要进一步了解将SLE与子宫内膜癌联系起来的潜在机制。
