Causal Associations between Gut Microbiota and Ovarian Cancer:A Two-Sam-ple Mendelian Randomization Study
Objective:To explore the causal relationship between Gut microbiota disorder and the risk of ovari-an 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 iden-tify specific bacteria associated with ovarian cancer risk.F<10 was used as the condition to remove the weak in-strumental 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.A-mong them,Cyanobacteria(OR 1.167),Bacteroidetes(OR 1.238),Bacteroidales(OR 1.329),Christen-senel-laceae(OR1.680)and Victivallis(OR 1.130)increased the risk of ovarian cancer(P<0.05),while Escherichia(OR0.786)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 sub-type(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 re-sults demonstrated the reliability of the research results.Conclusions:The analysis revealed the causal relation-ship between gut microbiota and the risk of ovarian cancer.Among the gut microbiota,Cyanobacteria,Bacte-roidetes,Bacteroidales,Christensenellaceae and Victivallis were the risk factors for ovarian cancer,while Esche-richia and Alphaproteobacteria were the protective factors.
Gut microbiotaMendelian randomizationWhole genome association studyCausal relationshipOvarian cancer