子宫内膜癌与乳腺癌的双向孟德尔随机化研究
Association between endometrial cancer and breast cancer:a bidirectional Mendelian randomization study
梁伟 1贡欣 1张晓晓 1李树苗1
作者信息
- 1. 北京中医药大学东方医院妇科,北京 100078
- 折叠
摘要
目的 采用双向两样本孟德尔随机化(MR)研究方法分析子宫内膜癌与乳腺癌的因果关联.方法 子宫内膜癌的遗传关联数据来自一项Meta分析,包括54 884人和9 464 330个SNP;乳腺癌的遗传关联数据来自乳腺癌协会联盟,包括228 951人和10 680 257个SNP.采用逆方差加权法(IVW),以子宫内膜癌相关的8个SNP为工具变量,乳腺癌为研究结局进行正向MR分析;以乳腺癌相关的112个SNP为工具变量,子宫内膜癌为研究结局进行反向MR分析.采用Cochran Q检验评估异质性,采用MR-PRESSO检验和MR-Egger回归法检验水平多效性,采用留一法检验结果的稳健性.结果 正向MR分析结果显示,与未患子宫内膜癌者相比,遗传学预测的子宫内膜癌患者的乳腺癌风险升高(OR=1.083,95%CI:1.037～1.132);反向MR分析结果显示,与未患乳腺癌者相比,遗传学预测的乳腺癌患者的子宫内膜癌风险升高(OR=1.070,95%CI:1.010～1.134).Cochran Q检验显示不存在异质性(P>0.05);MR-PRESSO检验和MR-Egger回归法均未发现工具变量的水平多效性(均P>0.05);留一法显示逐一剔除SNP后,MR分析结果稳健.结论 子宫内膜癌与乳腺癌之间存在双向因果关联.
Abstract
Objective To examine the causal relationship between endometrial cancer and breast cancer using bidirec-tional two-sample Mendelian randomization(MR)approach.Methods Genetic association data of endometrial cancer were collected through a meta analysis,including 54 884 participants and 9 464 330 single nucleotide polymorphisms(SNPs),and genetic association data of breast cancer were collected through the Breast Cancer Society Consortium,with 228 951 participants and 10 680 257 SNPs.A forward MR analysis was performed using the inverse variance weighted(IVW)method with 8 endometrial cancer-associated SNPs as instrumental variables and breast cancer as the study out-come,and a reverse MR analysis was performed with 112 breast cancer-associated SNPs as instrumental variables and endometrial cancer as the study outcome.The heterogeneity was assessed using the Cochran's Q test,the horizontal plei-otropy was assessed using the MR-PRESSO test and MR-Egger regression,and the robustness of the results was veri-fied with the leave-one-out.Results Forward MR analysis results showed that patients with genetically predicted endo-metrial cancer had an increased risk of breast cancer compared to those without endometrial cancer(OR=1.083,95%CI:1.037-1.132).Reverse MR analysis showed that patients with genetically predicted breast cancer had an increased risk of endometrial cancer compared to those without breast cancer(OR=1.070,95%CI:1.010-1.134).Cochran's Q test de-tected no heterogeneity(P>0.05),and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables(both P>0.05).Leave-one-out analysis showed robustness of the MR analysis results.Conclusion There are bidirectional causal relationship between endometrial cancer and breast cancer.
关键词
乳腺癌/子宫内膜癌/孟德尔随机化/因果关系Key words
breast cancer/endometrial cancer/Mendelian randomization/causal relationship引用本文复制引用
基金项目
首都卫生发展科研专项(首发2018-4-4204)
北京市中医药科技发展资金项目(QN-2020-18)
出版年
2024
NETL
NSTL
万方数据