Metformin cause cancer
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The Relationship Between Metformin and Cancer: A Comprehensive Review
Introduction to Metformin and Its Potential Anti-Cancer Properties
Metformin, a widely prescribed medication for type 2 diabetes, has garnered attention for its potential anti-cancer properties. This interest stems from various epidemiological studies and preclinical data suggesting that metformin may reduce cancer risk and improve survival outcomes in cancer patients .
Metformin and Cancer Incidence
General Cancer Incidence
Several systematic reviews and meta-analyses have investigated the association between metformin use and cancer incidence. A comprehensive umbrella review found strong evidence supporting the association between metformin use and decreased pancreatic cancer incidence, as well as highly suggestive evidence for improved colorectal cancer overall survival (OS). Additionally, a meta-analysis of epidemiologic studies reported a 31% reduction in overall cancer risk among diabetic patients taking metformin compared to other antidiabetic drugs. These findings were supported by another systematic review, which found significant reductions in the risk of liver, colorectal, and pancreatic cancers among metformin users .
Site-Specific Cancer Incidence
Breast Cancer
The relationship between metformin and breast cancer incidence is less clear. While preclinical studies and some observational data suggest a potential protective effect, randomized controlled trials (RCTs) have yielded disappointing results, particularly in the metastatic setting. A systematic review and meta-analysis found no significant association between metformin exposure and breast cancer incidence, although a 45% reduction in all-cause mortality was observed among breast cancer patients with type 2 diabetes.
Lung Cancer
Preliminary studies suggest that metformin may improve survival in high BMI lung cancer patients and inhibit lung cancer progression, potentially through its effects on the immune microenvironment of the lung. However, more research is needed to confirm these findings and determine the precise mechanisms involved.
Metformin and Cancer Mortality
General Cancer Mortality
Observational studies have consistently shown that metformin use is associated with a significant reduction in cancer mortality among diabetic patients. A systematic review and meta-analysis reported a 34% reduction in cancer mortality risk among metformin users. Another meta-analysis found similar results, with a pooled risk ratio of 0.66 for cancer mortality among metformin users compared to non-users.
Limitations and Need for Further Research
Despite the promising findings from observational studies, the evidence from RCTs is less conclusive. A meta-analysis of RCTs found no significant effect of metformin on cancer risk or all-cause mortality, highlighting the need for more long-term, well-designed trials to confirm the potential benefits of metformin as an anticancer agent.
Mechanisms of Action
The potential anti-cancer effects of metformin are thought to be mediated through several mechanisms. Metformin activates AMP-activated protein kinase (AMPK), which inhibits the mammalian target of rapamycin (mTOR) pathway, a key regulator of cell growth and proliferation. Additionally, metformin may reduce insulin and insulin-like growth factor-1 levels, decrease inflammation, and inhibit cancer stem cells, all of which could contribute to its anti-tumorigenic effects .
Conclusion
In summary, while observational studies suggest that metformin may reduce cancer risk and improve survival outcomes, the evidence from RCTs is less definitive. The potential anti-cancer mechanisms of metformin are complex and multifaceted, involving both AMPK-dependent and independent pathways. Further research, particularly long-term RCTs, is needed to confirm the role of metformin in cancer prevention and treatment.
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