Trans-ethnic Mendelian randomization study of systemic lupus erythematosus and common female hormone-dependent malignancies

作     者：Tingting Zhu Yantao Ding Xiaoli Xu Liyin Zhang Xuejun Zhang Yong Cui Lu Liu 

作者机构：Department of DermatologyThe First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China Institute of DermatologyAnhui Medical UniversityHefeiAnhui 230022China Inflammation and Immune Mediated Diseases Laboratory of Anhui ProvinceHefeiAnhui 230022China Department of Rheumatology and ImmunologyArthritis Research InstituteThe First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China Department of DermatologyWuxi Second Hospital Affiliated to Nanjing Medical UniversityWuxiJiangsu 214001China Department of DermatologyChina-Japan Friendship HospitalBeijing 100029China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2023年第136卷第21期

页      面：2609-2620页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by a grant from the Young Program of the National Natural Science Foundation of China(No.82003328) 

主　　题：Systemic lupus erythematosus Malignancy Causal inference Mendelian randomization 

摘      要：Background:Observational research has reported that systemic lupus erythematosus(SLE)is related to common female hormonedependent cancers,but the underlying causal effect remains *** study aimed to explore the causal association of these conditions by Mendelian randomization(MR)***:We selected instrumental variables for SLE from genome-wide association studies(GWASs)conducted in European and East Asian *** genetic variants for female malignant neoplasms were obtained from corresponding ancestry *** utilized inverse variance weighted(IVW)as the primary analysis,followed by sensitivity ***,we conducted multivariable MR(MVMR)to estimate direct effects by adjusting for the body mass index and ***,we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR ***:We found SLE was significantly negatively associated with overall endometrial cancer risk(odds ratio[OR]=0.961,95%confidence interval[CI]=0.935-0.987,P=3.57E
03)and moderately inversely related to endometrioid endometrial cancer(ENEC)(OR=0.965,95%CI=0.936-0.995,P=0.024)risk in the European population by *** replicated these results using other MR models and detected a direct effect by MVMR(overall endometrial cancer,OR=0.962,95%CI=0.941-0.983,P=5.11E
04;ENEC,OR=0.964,95%CI=0.940-0.989,P=0.005).Moreover,we revealed that SLE was correlated with decreased breast cancer risk(OR=0.951,95%CI=0.918-0.986,P=0.006)in the East Asian population by IVW,and the effect was still significant inMVMR(OR=0.934,95%CI=0.859-0.976,P=0.002).The statistical powers of positiveMRresults were all***:This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations,respectively,by MR analysis,which compensates for inherent limitations of observational research.