Unravelling the association between metformin and pan-cancers: Mendelian randomization combined with NHANES database analysis
Abstract Introduction An increasing number of studies have focused on the anti-tumor effect of metformin in recent years. However, the effect of metformin on different cancers remains controversial and lacks consensus. Methods A bidirectional two-sample Mendelian randomization (MR) design was used t...
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| Format: | Article |
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Springer
2025-03-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02021-4 |
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| author | Jia-Cheng Xiang Ye An Jian-Xuan Sun Jin-Zhou Xu Yi-Fan Xiong Shao-Gang Wang Qi-Dong Xia |
| author_facet | Jia-Cheng Xiang Ye An Jian-Xuan Sun Jin-Zhou Xu Yi-Fan Xiong Shao-Gang Wang Qi-Dong Xia |
| author_sort | Jia-Cheng Xiang |
| collection | DOAJ |
| description | Abstract Introduction An increasing number of studies have focused on the anti-tumor effect of metformin in recent years. However, the effect of metformin on different cancers remains controversial and lacks consensus. Methods A bidirectional two-sample Mendelian randomization (MR) design was used to assess causal relationships between metformin and 18 cancer types. Sensitivity analyses were conducted for reliability assessment. Multivariate Mendelian randomization (MVMR) analyses considered three relevant factors simultaneously. MR analysis based on gene proxies was conducted as well for further validation. Logistic regression models were constructed using National Health and Nutrition Examination Survey (NHANES) data (2013–2018) to evaluate the association between metformin and cancer. Results Two-sample MR analysis identified metformin as a protective factor for pan cancer, prostate, ovarian, breast, esophageal, colorectal, and lung cancer. However, metformin was found to be a risk factor for bladder cancer. MVMR analysis confirmed metformin’s significant protective effect on prostate and ovarian cancer. Logistic models based on NHANES data demonstrated metformin's significant protective effect against cancer in diabetes patients. Conclusion Our findings indicate a significant protective effect of metformin against prostate and ovarian cancer based on MR analysis. NHANES data further support a general protective effect of metformin against cancer. These findings warrant consideration of metformin in the context of cancer prevention and potential therapeutic strategies for prostate and ovarian cancer, though further research is needed to fully elucidate its mechanisms of action and establish its role in anti-cancer therapy. |
| format | Article |
| id | doaj-art-d46a35e394f74d05a67fa8b6269ff7b6 |
| institution | DOAJ |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-d46a35e394f74d05a67fa8b6269ff7b62025-08-20T03:05:56ZengSpringerDiscover Oncology2730-60112025-03-0116111810.1007/s12672-025-02021-4Unravelling the association between metformin and pan-cancers: Mendelian randomization combined with NHANES database analysisJia-Cheng Xiang0Ye An1Jian-Xuan Sun2Jin-Zhou Xu3Yi-Fan Xiong4Shao-Gang Wang5Qi-Dong Xia6Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Introduction An increasing number of studies have focused on the anti-tumor effect of metformin in recent years. However, the effect of metformin on different cancers remains controversial and lacks consensus. Methods A bidirectional two-sample Mendelian randomization (MR) design was used to assess causal relationships between metformin and 18 cancer types. Sensitivity analyses were conducted for reliability assessment. Multivariate Mendelian randomization (MVMR) analyses considered three relevant factors simultaneously. MR analysis based on gene proxies was conducted as well for further validation. Logistic regression models were constructed using National Health and Nutrition Examination Survey (NHANES) data (2013–2018) to evaluate the association between metformin and cancer. Results Two-sample MR analysis identified metformin as a protective factor for pan cancer, prostate, ovarian, breast, esophageal, colorectal, and lung cancer. However, metformin was found to be a risk factor for bladder cancer. MVMR analysis confirmed metformin’s significant protective effect on prostate and ovarian cancer. Logistic models based on NHANES data demonstrated metformin's significant protective effect against cancer in diabetes patients. Conclusion Our findings indicate a significant protective effect of metformin against prostate and ovarian cancer based on MR analysis. NHANES data further support a general protective effect of metformin against cancer. These findings warrant consideration of metformin in the context of cancer prevention and potential therapeutic strategies for prostate and ovarian cancer, though further research is needed to fully elucidate its mechanisms of action and establish its role in anti-cancer therapy.https://doi.org/10.1007/s12672-025-02021-4MetforminPan-cancerMendelian randomizationNHANES |
| spellingShingle | Jia-Cheng Xiang Ye An Jian-Xuan Sun Jin-Zhou Xu Yi-Fan Xiong Shao-Gang Wang Qi-Dong Xia Unravelling the association between metformin and pan-cancers: Mendelian randomization combined with NHANES database analysis Discover Oncology Metformin Pan-cancer Mendelian randomization NHANES |
| title | Unravelling the association between metformin and pan-cancers: Mendelian randomization combined with NHANES database analysis |
| title_full | Unravelling the association between metformin and pan-cancers: Mendelian randomization combined with NHANES database analysis |
| title_fullStr | Unravelling the association between metformin and pan-cancers: Mendelian randomization combined with NHANES database analysis |
| title_full_unstemmed | Unravelling the association between metformin and pan-cancers: Mendelian randomization combined with NHANES database analysis |
| title_short | Unravelling the association between metformin and pan-cancers: Mendelian randomization combined with NHANES database analysis |
| title_sort | unravelling the association between metformin and pan cancers mendelian randomization combined with nhanes database analysis |
| topic | Metformin Pan-cancer Mendelian randomization NHANES |
| url | https://doi.org/10.1007/s12672-025-02021-4 |
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