腸道菌群與膀胱癌因果關(guān)系的孟德爾隨機化法分析

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Analysis of the causal relationship between gut microbiota and bladder cancer with Mendelian randomization

GUO Xuyan，LUO Zhirong，XUE Qi，JI Yunhua，TAN Xiao，JIAO Yong （Department of Urology，Tangdu Hospital，Air Force Medical University，Xi'an 710o38，China）

ABSTRACT：ObjectivePrevious observational studies have confirmed the correlation between gut microbiota and blader cancer，butthecausalrelationshipisstillunclear.Thisstudyaimedtoexplorethecausalrelationshipbetweenthemwith Mendelian randomization.MethodsGenetic variation summary data of 211 gut microbiotaand bladder cancer genome-wide association studies（GWAS）were obtained from the MiBioGen Consortium and Fingen database.Single nucleotide polymorphisms（SNPs）closelyrelated to these studies were screened as instrumental variables.Thecausal relationship between gut microbiota and bladdercancer were analyzed with inverse variance weighting（IVW），MR-Eger，weightedmedian， maximumlikelihood，robust adjustmentfeature score and MR-PREsSO，with IVWas the primaryanalysis method.Additionally， sensitivity analysis was used to test the heterogeneity （Cochran Q ）and horizontal pleiotropy （MR-Egger intercept term and globaltest from MR-PRESSO estimator）to ensure the robustness of the results.ResultsThe IVWresults indicated that Lachnospiraceae UCG004 （OR：1.42），Desulfovibrionales（Order） （OR：1.48），Eubacterium ruminantium group （ （OR：1.33） ， Olsenella（OR：1.24），Ruminococcaceae UCGoo2（OR：1.39），Ruminococcaceae UCG005 （ OR：1.42： and Ruminococcaceae UCG013 （ OR：1.64? ）significantly increased the risk of bladder cancer.Conversely，Bacteroidetes（Phylum） （OR：0.61） ， Eubacterium brachy group （OR ： O. 8O）， Ruminococcaceae UCGo04 （OR： 0.73），Rikenelaceae（Family） （OR：0. 67） ， Lachnospiraceae ND3oo7 group （OR ：0.47），Adlercreutzia （OR ：0.73） and an unknow genus （OR：0.75） were associated with areduced risk of blader cancer.Sensitivity analyses did not reveal any heterogeneityor horizontal pleiotropy.Conclusion This studyreveals thecausalroleof14 gut microbiotain thepathogenesis of bladdercancer，among which Lachnospiraceae UCG004，Desulfovibrionales （Order），Eubacterium ruminantium group，Olsenella ，Ruminococcaceae UCG002 ， Ruminococcaceae UCG005 and Ruminococcceae UCGol3 are risk factors for bladder cancer，while Bacteroidetes （Phylum），Eubacterium brachy group，Ruminococcaceae UCGo04，Rikenellaceae（Family），Lachnospiraceae ND3oo7group，Adlercreutzia and anunknown genus are the protective factors.

KEY WORDS： gut microbiota； bladder cancer; causal relationship；Mendelian randomization摘要：目的以往的觀察性研究已證實腸道菌群與膀胱癌存在相關(guān)性，但二者間的因果關(guān)系尚不明確。（剩余16250字）