肠道菌群与卵巢癌风险的双样本孟德尔随机化研究

Causal Associations between Gut Microbiota and Ovarian Cancer:A Two-Sample Mendelian Randomization Study

目的:分析肠道菌群紊乱与卵巢癌发病风险的因果关系。方法:MiBioGen联盟官网获取人类肠道菌群的全基因组关联研究(GWAS)数据作为暴露因素,从卵巢癌协会联盟(OCAC)获得卵巢癌数据作为结局,使用孟德尔随机化(MR)研究分析肠道菌群与卵巢癌发病风险之间的因果关系。使用F<10作为条件删除弱工具变量,科克伦Q参数进行异质性检验;MR-Egger法进行水平多效性检验;MR-PRESSO法和留一法剔除异常的工具变量。结果:MR分析表明有2个门、1个纲、1个目、1个科和2个属的菌群与卵巢癌致病风险有因果关系。其中,蓝藻门(OR 1.167)、拟杆菌门(OR 1.238)、拟杆菌目(OR 1.329)、克里斯滕森菌科(OR 1.680)和食物谷菌属(OR 1.130)会增加卵巢癌风险(P<0.05),而埃希菌属(OR 0.786)和变形菌纲(OR 0.763)会降低卵巢癌风险(P<0.05)。此外,不同肠道菌群与不同类型卵巢癌存在因果关系,其中拟杆菌门(OR 1.354)、拟杆菌目(OR 1.400)、克里斯滕森菌科(OR 1.907)增加高级别浆液性癌发病风险(P<0.05),而变形菌纲(OR 0.773)降低高级别浆液性癌发病风险(P<0.05);蓝藻门(OR 1.638)增加透明细胞性癌风险(P<0.05),变形菌纲(OR 0.454)降低黏液性癌风险(P<0.05)。敏感性分析结果证明该研究结果可靠。结论:肠道微生物群与卵巢癌发病风险有因果关系,其中蓝藻门、拟杆菌门、拟杆菌目、克里斯滕森菌科和食物谷菌属为卵巢癌发病危险因素,而埃希菌属和变形菌纲为保护因素。

Objective:To explore the causal relationship between Gut microbiota disorder and the risk of ovarian cancer.Methods:The data of gut microbiome from Whole Genome Association Study(GWAS)by using the MiBioGen Alliance official website was used as the exposure factor.The ovarian cancer data was obtained from the ovarian cancer association alliance(OCAC)as the outcome.Mendelian randomization(MR)was used to identify specific bacteria associated with ovarian cancer risk.F<10 was used as the condition to remove the weak instrumental variables estimation.The Cochrane Q parameter was used for heterogeneity testing.The MR-Egger method was used for horizontal pleiotropy testing,while MR-PRESSO method and leave one method were used to eliminated abnormal instrumental variables.Results:MR analysis showed that there were causal relationships between gut microbiota including 2 phyla,1 class,1 order,1 family and 2 genus and the risk of ovarian cancer.Among them,Cyanobacteria(OR 1.167),Bacteroidetes(OR 1.238),Bacteroidales(OR 1.329),Christen-senellaceae(OR 1.680)and Victivallis(OR 1.130)increased the risk of ovarian cancer(P<0.05),while Escherichia(OR 0.786)and Alphaproteobacteria(OR 0.763)decreased the risk of ovarian cancer(P<0.05).In addition,there were causal relationships between gut microbiota and ovarian cancer subtypes.Among them,Bacteroidetes(OR 1.354),Bacteroidales(OR 1.400),and Christensenellaceae(OR 1.907)increased the risk of high-grade serous subtype(P<0.05),while Alphaproteobacteria(OR 0.773)decreased the risk of high-grade serous subtype(P<0.05).Moreover,Cyanobacteria(OR 1.638)increased the risk of clear cell subtype(P<0.05),while Alphaproteobacteria(OR 0.454)decreased the risk of mucinous subtype(P<0.05).The sensitivity analysis results demonstrated the reliability of the research results.Conclusions:The analysis revealed the causal relationship between gut microbiota and the risk of ovarian cancer.Among the gut microbiota,Cyanobacteria,Bacteroidetes,Bacteroidales,Christensenellaceae and Victivallis were the risk factors for ovarian cancer,while Escherichia and Alphaproteobacteria were the protective factors.