PDF(Pubmed)
Abstract：
UNASSIGNED: Numerous studies have reported that metformin can reduce the risk of tumor development. However, some of the results of these studies are conflicting, necessitating a more reliable evaluation.
UNASSIGNED: We conducted a Mendelian randomization phenome-wide association study (MR-PheWAS) of tumors to explore the causal relationship between metformin and tumors. Two cohorts of patients taking metformin were obtained from the UK Biobank. Complete phenotype data of the tumors were obtained from FinnGen_R10. We elucidated the causal relationship using a two-sample Mendelian randomization (MR) analysis. More importantly, we conducted a meta-analysis to ensure relatively unbiased results. In the MR analysis, we used the inverse-variance weighted (IVW) method as the main outcome indicator. Subsequently, two cohorts were integrated for the meta-analysis. Finally, we investigated the mechanisms through mediational MR analysis.
UNASSIGNED: MR analysis revealed that metformin might have a causal relationship with 13 tumor-associated phenotypes in the training cohort. Four phenotypes were validated in the testing cohort. In the training and testing cohorts, metformin exhibited a protective effect against brain meningiomas and malignant neoplasms of the breast (HER-positive), oral cavity, tonsils, and the base of the tongue. Intriguingly, after integrating the results of the two cohorts for the meta-analysis, 12 results were statistically significant. Mediational MR analysis suggested that the effects of metformin on brain meningiomas may be weakened by the presence of the family Oxalobacteraceae.
UNASSIGNED: Metformin exhibits potential preventive and therapeutic effects on four types of tumors: brain meningioma, malignant neoplasms of the breast (HER-positive), oral cavity and tonsils, and the base of the tongue. Large randomized controlled trials are required to confirm these findings.
UNASSIGNED: We conducted a Mendelian randomization phenome-wide association study (MR-PheWAS) of tumors to explore the causal relationship between metformin and tumors. Two cohorts of patients taking metformin were obtained from the UK Biobank. Complete phenotype data of the tumors were obtained from FinnGen_R10. We elucidated the causal relationship using a two-sample Mendelian randomization (MR) analysis. More importantly, we conducted a meta-analysis to ensure relatively unbiased results. In the MR analysis, we used the inverse-variance weighted (IVW) method as the main outcome indicator. Subsequently, two cohorts were integrated for the meta-analysis. Finally, we investigated the mechanisms through mediational MR analysis.
UNASSIGNED: MR analysis revealed that metformin might have a causal relationship with 13 tumor-associated phenotypes in the training cohort. Four phenotypes were validated in the testing cohort. In the training and testing cohorts, metformin exhibited a protective effect against brain meningiomas and malignant neoplasms of the breast (HER-positive), oral cavity, tonsils, and the base of the tongue. Intriguingly, after integrating the results of the two cohorts for the meta-analysis, 12 results were statistically significant. Mediational MR analysis suggested that the effects of metformin on brain meningiomas may be weakened by the presence of the family Oxalobacteraceae.
UNASSIGNED: Metformin exhibits potential preventive and therapeutic effects on four types of tumors: brain meningioma, malignant neoplasms of the breast (HER-positive), oral cavity and tonsils, and the base of the tongue. Large randomized controlled trials are required to confirm these findings.
摘要：
■许多研究报道二甲双胍可以降低肿瘤发展的风险。然而,这些研究的一些结果是相互矛盾的，需要更可靠的评估。
■我们进行了肿瘤的孟德尔随机全表型关联研究（MR-PheWAS），以探讨二甲双胍与肿瘤之间的因果关系。两组服用二甲双胍的患者来自英国生物银行。肿瘤的完整表型数据从FinnGen_R10获得。我们使用双样本孟德尔随机化（MR）分析阐明了因果关系。更重要的是,我们进行了荟萃分析,以确保结果相对公正.在MR分析中，我们使用逆方差加权(IVW)方法作为主要结果指标。随后，纳入两个队列进行荟萃分析.最后,我们通过中介MR分析研究了机制.
■MR分析显示，在训练队列中，二甲双胍可能与13种肿瘤相关表型有因果关系。在测试队列中验证了四种表型。在培训和测试队列中，二甲双胍对脑脑膜瘤和乳腺恶性肿瘤（HER阳性）具有保护作用，口腔,扁桃体,和舌根。有趣的是，在整合两个队列的结果进行荟萃分析后，12成果具有统计学意义。中介MR分析表明，二甲双胍对脑脑膜瘤的作用可能会因草酸杆菌科的存在而减弱。
■二甲双胍对四种类型的肿瘤具有潜在的预防和治疗作用：脑脑膜瘤，乳腺恶性肿瘤（HER阳性），口腔和扁桃体，和舌根。需要大型随机对照试验来证实这些发现。
■我们进行了肿瘤的孟德尔随机全表型关联研究（MR-PheWAS），以探讨二甲双胍与肿瘤之间的因果关系。两组服用二甲双胍的患者来自英国生物银行。肿瘤的完整表型数据从FinnGen_R10获得。我们使用双样本孟德尔随机化（MR）分析阐明了因果关系。更重要的是,我们进行了荟萃分析,以确保结果相对公正.在MR分析中，我们使用逆方差加权(IVW)方法作为主要结果指标。随后，纳入两个队列进行荟萃分析.最后,我们通过中介MR分析研究了机制.
■MR分析显示，在训练队列中，二甲双胍可能与13种肿瘤相关表型有因果关系。在测试队列中验证了四种表型。在培训和测试队列中，二甲双胍对脑脑膜瘤和乳腺恶性肿瘤（HER阳性）具有保护作用，口腔,扁桃体,和舌根。有趣的是，在整合两个队列的结果进行荟萃分析后，12成果具有统计学意义。中介MR分析表明，二甲双胍对脑脑膜瘤的作用可能会因草酸杆菌科的存在而减弱。
■二甲双胍对四种类型的肿瘤具有潜在的预防和治疗作用：脑脑膜瘤，乳腺恶性肿瘤（HER阳性），口腔和扁桃体，和舌根。需要大型随机对照试验来证实这些发现。
