服用阿司匹林与子宫内膜癌发病风险的孟德尔随机化关系

A Mendelian randomization study of aspirin use and the risk of endometrial cancer

目的利用两样本孟德尔随机化研究方法,探讨服用阿司匹林与子宫内膜癌发病风险间的因果关系。方法进行两样本孟德尔随机化分析,利用人类全基因组关联分析(GWAS)计算服用阿司匹林和子宫内膜样癌(EEC)及非子宫内膜样癌(NEC)发病风险之间的潜在因果关系。其中服用阿司匹林和EEC、NEC相关的单核苷酸多态性(SNP)数据均来自于GWAS catalog数据库。选择与服用阿司匹林强关联的SNPs作为工具变量,并借助逆方差加权法(IVW)、加权中位数法、MR Egger、简单模型、加权模型等多种统计学方法,以比值比(OR)评价服用阿司匹林与EEC及NEC风险之间的因果关系。结果共纳入6个SNP作为工具变量,IVW方法显示服用阿司匹林可降低EEC的发病风险(OR=0.02,95%CI:0~0.28,P=0.005),而服用阿司匹林与NEC的发病风险之间无类似的因果关系(OR=0.00,95%CI:0.00~16.26,P=0.199)。另外几种统计学方法的结果与IVW方法显示的结果一致。敏感性分析表明,在对两类组织类型子宫内膜癌的研究中,异质性、水平多效性及留一法检验均显示工具变量的可靠性,无明显偏倚。结论服用阿司匹林可降低EEC的发病风险,通过更深层次探讨阿司匹林对EEC的生物学机制,有望对子宫内膜癌的早期防治产生重要影响。

Objective To investigate the causal relationship between aspirin use and the risk of endometrial cancer using the two-sample Mendelian randomization method.Methods A two-sample Mendelian randomization analysis was performed to estimate the potential causal relationship between aspirin use and endometrial endometrioid carcinoma(EEC)and non-endometrioid carcinoma(NEC)using GWAS genome-wide data.The single nucleotide polymorphism(SNP)data associated with aspirin use,EEC and NEC were obtained from the GWAS catalog database.SNPs with strong association with aspirin use were selected as instrumental variables and analyzed with inverse variance weighted(IVW),weighted median,MR Egger,simple mode and weighted mode.The causal relationship between aspirin use and risk of EEC and NEC was evaluated with odds ratio(OR).Results A total of 6 SNPs were included as instrumental variables,and the IVW showed that aspirin administration reduced the incidence of EEC(OR=0.02,95%CI:0-0.28,P=0.005),while no causal relationship was found between aspirin use and the risk of NEC(OR=0.00,95%CI:0.00-16.26,P=0.199).The results of other methods were consistent with those shown by IVW.Sensitivity analysis indicated that heterogeneity,horizontal pleiotropy and leave-one-out tests showed reliability of instrumental variables in different tissue types of endometrial cancer with no significant bias in the results.Conclusion Aspirin can reduce the risk of EEC.Exploring the biological mechanism of aspirin on EEC at a deeper level has important implications for the early prevention and treatment of endometrial cancer.