基于两样本孟德尔随机化探索子宫肌瘤与乳腺癌的因果关系

doi:10.6040/j.issn.1671-7554.0.2022.1021

摘要/Abstract

摘要： 目的探索子宫肌瘤(ULs)与乳腺癌(BC)的因果关系。方法采用两样本孟德尔随机化方法,使用公开的来自不同样本的、欧洲人的全基因组关联研究中的遗传数据,以ULs作为暴露,其单核苷酸多态性(SNPs)作为工具变量,BC作为结局变量。另外,对5种分子亚型BC进行亚组分析。运用Cochran的Q统计量检验SNPs的异质性,MR-Egger法检验多效性,逆方差加权、MR-Egger法、加权中位数法和MR-PRESSO法进行因果推断。通过R软件进行数据分析和可视化处理。结果最终纳入25个ULs的SNPs;异质性检验提示,部分亚组存在异质性(P<0.01);多效性检验没有发现显著的水平多效性(P>0.05);因果推断结果显示,基因预测的ULs与整体BC间没有因果关系(逆方差加权法:OR=0.98,95%CI:0.86~1.12,P=0.79),与5种亚型BC间也没有发现因果关系(P>0.01)。结论没有发现在欧洲人中ULs与整体BC的风险增加有因果关系,也不支持ULs与某一亚型BC有因果关系。

关键词: 子宫肌瘤, 乳腺癌, 分子亚型, 孟德尔随机化, 因果关系

Abstract: Objective To investigate the causal relationship between uterine leiomyomas(ULs)and breast cancer(BC). Methods The study employed a two-sample Mendelian randomization(MR)method, the European genetic data from published genome-wide association study, and ULs as exposure, single nucleotide polymorphisms(SNPs)of ULs as instrumental variables, and BC as outcome variable. In addition, 5 molecular subtypes of BC were analyzed as outcome variables. The heterogeneity of SNPs was determined with Cochrans Q test, and the pleiotropy was determined with MR-egger. Inverse variance weighted(IVW), MR-Egger, weighted median and MR-PRESSO were used to evaluate the causal relationship of ULs with BC. The R software was used for data analysis and visualization processing. Results A total of 25 SNPs of ULs were finally extracted. Cochrans Q test suggested that heterogeneity existed among some subgroups(P<0.01). No pleiotropy was observed(P>0.05). MR analysis showed that there was no causal relationship between ULs predicted by gene and overall BC(IVW: OR=0.98, 95%CI: 0.86-1.12, P=0.79), and there was no causal relationship with 5 molecular subtypes of BC(P>0.01). Conclusion There is no causal relationship between ULs and increased risk of overall BC in Europeans, and no causal relationship between ULs and any molecular subtype of BC.

Key words: Uterine leiomyomas, Breast cancer, Molecular subtype, Mendelian randomization, Causal relationship

中图分类号:

R737.33

张娜娜,赵一鸣,刘新敏. 基于两样本孟德尔随机化探索子宫肌瘤与乳腺癌的因果关系[J]. 山东大学学报 (医学版), 2023, 61(8): 86-93.

ZHANG Nana, ZHAO Yiming, LIU Xinmin. Causal relationship between uterine leiomyomas and breast cancer: a two-sample Mendelian randomization study[J]. Journal of Shandong University (Health Sciences), 2023, 61(8): 86-93.

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