基于孟德尔随机化分析的肠道菌群和17种癌症因果效应关系研究

Causal relationship between gut microbiota and 17 types of cancer based on mendelian randomization analysis

目的采用两样本孟德尔随机化(MR)分析法评估特定肠道菌群与不同类型癌症之间的因果关系。方法使用8956例德国人的肠道菌群全基因组关联研究(GWAS)汇总数据,提取与430种肠道菌群特征显著相关的单核苷酸多态性(SNP)变异位点作为工具变量(IV),以包括17种癌症的泛癌GWAS汇总数据作为结局,采用两样本MR分析肠道菌群与泛癌之间的因果关系,分析结果以逆方差加权法为主。同时,通过敏感性分析检验异质性和水平多效性以保证结果的稳定性。结果17种不同肠道菌群的遗传易感性分别与11种不同类型癌症的发生发展存在因果关系。结论通过探究不同类型肠道菌群与泛癌的因果关系,发现特定的肠道菌群与癌症之间存在潜在的因果关系,这些菌群可能成为新的生物标志物,为癌症的预防、早期筛查和治疗提供了新的思路。

Objective To assess causal associations between specific gut microbiota and different types of cancer by using the two⁃sample Mendelian randomization(MR)analysis method.Methods On the basis of summary statistics of gut microbiota from a genome⁃wide association study(GWAS)conducted in German population(n=8956),single nucleotide polymorphisms(SNPs)that were significantly associated with 430 gut microbiota features were extracted as instrumental variables(IVs).Summary statistics from the GWAS of 17 types of cancer were used as outcomes.Two⁃sample MR analysis was used to explore the causal relationship between gut microbiota and pan⁃cancer,where the analysis results were dominated by inverse variance weighting.Meanwhile,sensitivity analyse of heterogeneity and horizontal pleiotropy test were done to keep the stability of results.Results The genetic susceptibility of 17 gut microbiota features was causally associated with the occurrence and development of 11 different types of cancer,respectively.Conclusion By exploring the causal relationship between different gut microbiota features and pan⁃cancer,this study has found a potential causal relationship between specific gut microbiota features and cancer,and these gut microbiota may become new biomarkers to provide new ideas for cancer prevention,early screening,and treatment.