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Univariable MR used IVW as primary with robust adjusted profile scores, weighted median, and MR Egger as supplementary methods, plus Cochran Q, Egger intercept, and leave-one-out sensitivity checks. Multivariable MR assessed direct 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and risk of five common cancers: A univariable and multivariable Mendelian randomization study  \nZixin Wei1 | Biying Yang2,3 | Tiantian Tang1 | Zijing Xiao4 | Fengzhan Ye1 | Xiaoyu Li5 | Shangbin Wu6 | Jin-gang Huang7 | Shanping Jiang1   \n1Department of Pulmonary and Critical Care Medicine, SunYat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China 2Department of Neurology, SunYatSen Memorial Hospital, SunYat-Sen University, Guangzhou, Guangdong, China  \n3Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China  \n4Guangzhou Medical University, Guangzhou, Guangdong, China 5Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China 6Department of Pediatrics, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China  \n7Medical Research Center, SunYat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou, Guangdong, China  \nCorrespondence  \nShangbin Wu, Department of Pediatrics, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China. [Email:](Email: w15018723655@163.com)[ w15018723655@163.com](Email: w15018723655@163.com)  \nAbstract  \nBackground: Previous studies have linked gut microbiota with cancer etiology, but the associations for specific gut microbiota are causal or owing to bias remain to be elucidated.  \nMethods: We performed a two-sample Mendelian randomization (MR) analysis to assess the causal effect of gut microbiota on cancer risk. Five common cancers, including breast, endometrial, lung, ovarian, and prostate cancer as well as their subtypes (sample sizes ranging from 27,209 to 228,951) were included as the outcomes. Genetic information for gut microbiota was obtained from a genome-wide association study (GWAS) comprising 18,340 participants. In univariable MR (UVMR) analysis, the inverse variance weighted (IVW) method was conducted as the primary method, with the robust adjusted profile scores, weighted median, and MR Egger used as supplementary methods for causal inference. Sensitivity analyses including the Cochran Q test, Egger intercept test, and leave-one-out analysis were performed to verify the robustness of the MR results. Multivariable MR (MVMR) was performed to evaluate the direct causal effects of gut microbiota on the risk of cancers.  \nResults: UVMR detected a higher abundance of genus Sellimonas predicted a higher risk of estrogen receptor-positive breast cancer (OR = 1.09, 95% CI 1.05–1. 14, p = 2.01 × 10−5), and a higher abundance of class Alphaproteobacteria was associated with a lower risk of prostate cancer (OR = 0. 84, 95% CI 0.75–0. 93, p = 1.11 × 10−3) . Sensitivity analysis found little evidence of bias in the current study. MVMR further confirmed that genus Sellimonas exerted a direct effect on breast cancer, while the effect of class Alphaproteobacteria on prostate cancer was driven by the common risk factors of prostate cancer.  \nZixin Wei, Biying Yang, and Tiantian Tang—Equal contribution.  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.  \nJin-gang Huang, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China. [Email:](Email: huangjg35@mail.sysu.edu.cn)[ huangjg35@mail.sysu.edu.cn](Email: huangjg35@mail.sysu.edu.cn)  \nShanping Jiang, Department of Pulmonary and Critical Care Medicine, SunYat-Sen Memorial Hospital,  \nSun Yat-Sen University, Guangzhou, Guangdong, China. [Em","cbCaieNru5KYr2Nt","https://ap.wps.com/l/cbCaieNru5KYr2Nt","pdf",1956934,13,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Introduction","[{\"question\":\"What research question does the study address?\",\"answer\":\"The study tests whether gut microbiota has a causal effect on the risk of five common cancers and related subtypes.\"},{\"question\":\"How is causality assessed in this research?\",\"answer\":\"It uses two-sample Mendelian randomization with both univariable MR (UVMR) and multivariable MR (MVMR) approaches, combining primary and sensitivity methods to evaluate robustness.\"},{\"question\":\"Which gut microbiota signatures were linked to cancer risk in univariable MR?\",\"answer\":\"UVMR associated higher predicted abundance of genus Sellimonas with increased estrogen receptor-positive breast cancer risk and higher abundance of class Alphaproteobacteria with decreased prostate cancer risk.\"}]","Gut microbiota and risk of five common cancers - A univariable and multivariable Mendelian randomization study | PDF",1790233213,33]