摘要
目的 采用两样本孟德尔随机化方法探讨摄入咖啡与前列腺癌之间是否存在因果关系.方法 摄入咖啡(暴露)与前列腺癌(结局)的全基因组关联研究数据来自英国生物样本库中两个独立的数据集,利用逆方差加权法、加权中位数法以及MR-Egger法进行两样本孟德尔随机化研究,以OR值及95％CI代表摄入咖啡与前列腺癌的关联.此外,采用MR-Egger法进行多效性检验及异质性检验,留一法进行敏感性分析.结果 总共筛选38个SNP作为工具变量,逆方差加权法显示摄入咖啡可能降低前列腺癌风险(OR=0.994,95％CI:0.990～0.999,P=0.009),加权中位数法得到的结论一致(OR=0.991,95％CI:0.985～0.999,P=0.018),不过MR-Egger回归未发现摄入咖啡与前列腺癌存在因果关系(OR=0.992,95％CI:0.983～1.000,P=0.084).MR-Egger法显示工具变量不存在多效性(截距=4.2E-5,P=0.581)及异质性(Q=27.20,P=0.854),敏感性分析显示结论稳健.结论 孟德尔随机化分析结果表明摄入咖啡可能减少前列腺癌发病风险.
Abstract
Objective To assess the causal relationship between coffee intake and prostate cancer risk by using the two-sample Mendel randomization(MR)method.Methods The genome-wide association study(GWAS)data on coffee intake(exposure)and prostate cancer(outcome)were obtained from two independent data sets in UK Biobank.The inverse variance weighted method(IVW),weighted median estimator method(WME),and MR-Egger method were used for MR analyses.The OR value and 95％CI were used to represent the association between coffee intake and prostate cancer.In addition,the MR-Egger method was performed for pleiotropic and heterogeneity tests,and the leave-one-out method was used for sensitivity analysis.Results A total of 38 SNP were selected as instrumental variables.The IVW method showed that coffee intake might reduce the risk of prostate cancer(OR=0.994;95％CI:0.990-0.999;P=0.009).The WME method obtained the same conclusions(OR=0.991;95％CI:0.985-0.999;P=0.018),but MR-Egger regression did not find a causal relationship between coffee intake and prostate cancer(OR=0.992;95％CI:0.983-1.000;P=0.084).The MR-Egger method showed no pleiotropy(intercept=4.2E-5;P=0.581)or heterogeneity(Q=27.20;P=0.854)among the instrumental variables.The sensitivity analysis indicated that the conclusion was robust.Conclusion Two-sample Mendel randomization analysis reveals that coffee consumption might reduce the risk of prostate cancer.
维普
万方数据