Antidiabetes Drugs Correlate With Decreased Risk of Lung Cancer: A Population-Based Observation in Taiwan

Lai, Shih‐Wei; Liao, Kuan‐Fu; Chen, Pei–Chun; Tsai, Pang-Yao; Hsieh, Dennis P. H.; Chen, Ching‐Chu

doi:10.1016/j.cllc.2011.10.002

Cited by 123 publications

(114 citation statements)

References 19 publications

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“…Metformin has been related with lower incidence of cancer among type 2 diabetes patients [70]. Many studies support the notion that the use of metformin results in lower incidence of cancer [71][72][73][74][75]. Lung, pancreatic, prostate, breast, ovarian, and hepatocellular cancer incidence has been found to be lower among patients receiving metformin [76][77][78][79][80][81][82].…”

Section: Metformin Cancer Prevention and Mortalitymentioning

confidence: 90%

Metformin and Cancer

Vallianou¹,

Evangelopoulos²,

Kazazis³

2013

Rev Diabet Stud

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■ AbstractMetformin is well-known as an anti-diabetic drug, but it seems to possess anti-cancerous properties as well. Adenosine monophosphate-activated protein kinase (AMPK) is a highly conserved regulator of the cellular response to the presence of low energy in all eukaryotic cells. It is considered a key sensor of the balance of cellular ATP and AMP concentrations. LKB1 serine/threonine kinase is a divergent yet evolutionarily well-conserved kinase, biochemically sufficient to activate AMPK in vitro and genetically required for AMPK activation. Because of this potent connection to AMPK, LKB1 may act as a central regulator of metabolism in vivo. Once activated, AMP kinase phosphorylates the transcriptional activator TorC2, thereby blocking its nuclear translocation and inhibiting the expression of genes involved in gluconeogenesis. Data suggest that LKB1/AMPK signaling plays a role in protection from apoptosis, specifically in response to agents that increase the cellular AMP/ATP ratio. Active AMPK signaling offers a protective effect by providing the cell with time to reverse the aberrantly high ratio of AMP/ATP. If unable to reverse this ratio, the cell will eventually undergo cell death. These observations offer the provocative suggestion of a potential therapeutic window in which LKB1-deficient tumor cells may be acutely sensitive to AMP analogues or sensitized to cell death by other stimuli when treated in combination with agents that increase the AMP/ATP ratio. LKB1 therefore is a classical tumor suppressor. AMPK is a direct LKB1 substrate. A consequence of AMPK activation by LKB1 is the inhibition of the mammalian target of rapamycin (mTOR) C1 pathway. Metformin's anti-cancerous properties have been demonstrated in various cancer cells in vitro, such as lung, pancreatic, colon, ovarian, breast, prostate, renal cancer cells, melanoma, and even in acute lymphoblastic leukemia cells. To test metformin's action in vivo, mice were implanted with transformed mammary epithelial cells and treated with three cycles of metformin and with the anthracycline doxorubicin. When combined with doxorubicin, metformin wiped out tumors and prevented recurrence. Metformin alone had no effect, and doxorubicin as a single agent initially shrank tumors, but they regrew later. Virtually no cancer stem cells were recovered immediately after treatment and the complete response was sustained for nearly two months. Further studies are needed to assess the anti-cancerous potentials of metformin in vivo. This article reviews the current knowledge on the actions of LKB1/AMPK and the effectiveness of metformin in cancer, specifically in diabetes patients.

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Section: Metformin Cancer Prevention and Mortalitymentioning

confidence: 90%

Metformin and Cancer

Vallianou¹,

Evangelopoulos²,

Kazazis³

2013

Rev Diabet Stud

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“…However, the potential biological links between the two diseases are not well understood. Evidence from observational studies suggests that certain glucose-lowering therapies are associated with increased or reduced risks of cancer (6,(12)(13)(14)(15)(16)(17)(18)(19). Although previous research studies have revealed the linkages between DM and colorectal, liver and pancreatic cancers (7)(8)(9)11), the associations between DM and other types of gastrointestinal (GI) cancers have not been well studied and the evidence is inconclusive.…”

Section: Introductionmentioning

confidence: 89%

Increased Risk of Gastrointestinal Malignancy in Patients with Diabetes Mellitus and Correlations with Anti-Diabetes Drugs: A Nationwide Population-based Study in Taiwan

et al. 2013

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Objective Although the major cause of morbidity and mortality in patients with diabetes mellitus (DM) is cardiovascular disease, DM is also associated with certain site-specific cancers. However, whether DM is associated with an increased risk of cancer of the digestive tract remains undetermined. A nationwide, population-based database in Taiwan was analyzed to explore the relationship between DM and cancer of the digestive organs. Methods From 2000 to 2007, a study cohort consisting of 39,515 patients with newly diagnosed diabetes without a previous diagnosis of gastrointestinal (GI) cancer was identified from the National Health Insurance Research Database in Taiwan. A control cohort of 79,030 age-and sex-matched non-diabetic subjects was selected to compare the occurrence of GI malignancies between the two groups. The association between the incidence of GI cancers and the use of glucose-lowering therapies was also investigated. Results During the 7-year follow-up period, GI cancers developed in 929 diabetic patients (2.35%) and 1,126 subjects (1.42%) in the comparison cohort. DM was associated with a 2.75-fold (95% confidence interval (CI), 2.51-3.02) higher risk of developing GI malignancy. Among GI cancers, the incidences of stomach (adjusted hazard ratio (HR), 1.49; 95% CI, 1.16-1.92), liver (adjusted HR, 2.65; 95% CI, 2.29-3.07), colon (adjusted HR, 1.58; 95% CI, 1.28-1.94) and pancreatic cancers (adjusted HR, 4.35; 95% CI, 2.93-6.47) were significantly increased in the patients with DM. An analysis of the effects of various glucose-lowering therapies in the diabetic patients revealed the use of α-glucosidase inhibitors to be associated with a lower risk of hepatic cancer (adjusted HR, 0.62; 95% CI, 0.4-0.94). Thiazolidinedione (TZD) treatment was associated with lower stomach (adjusted HR, 0.11; 95% CI, 0.02-0.82) and hepatic cancer risks (adjusted HR, 0.46; 95% CI, 0.29-0.73), while sulfonylurea use was associated with a lower colon cancer risk (adjusted HR, 0.74; 95% CI, 0.51-1.09) and a higher pancreatic cancer risk (adjusted HR, 2.36; 95% CI, 1.21-4.61). Conclusion Patients with DM have an increased risk of GI malignancy that may be affected by the use of different categories of glucose-lowering therapies.

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“…This represents a decrease of risk by nearly 33% in the incidence of lung cancer. A similar study co nducted in Taiwan 4 demo nst rat ed no increased risk in the incidence of lung cancer in patients with diabetes mellitus, but did demonstrate a statistically significant decrease in its incidence with the use of metformin. This analysis of drug usage was restricted to patients with diabetes only.…”

Section: Metformin and Lung Cancer Incidencementioning

confidence: 99%

Metformin and lung cancer

Yendamuri

2014

JCSR

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Metformin, a commonly used anti-diabetic drug has emerged as a potential anti-cancer drug. Over the last few years, a mass of epidemiologic, outcomes and preclinical data has emerged demonstratic the potential clinical relevance and the mechanistic basis of the anti-cancer activity of this well tolerated drug in lung cancer. This review article summarizes this evidence that supports the trial of this drug in in lung cancer.

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Antidiabetes Drugs Correlate With Decreased Risk of Lung Cancer: A Population-Based Observation in Taiwan

Cited by 123 publications

References 19 publications

Metformin and Cancer

Metformin and Cancer

Increased Risk of Gastrointestinal Malignancy in Patients with Diabetes Mellitus and Correlations with Anti-Diabetes Drugs: A Nationwide Population-based Study in Taiwan

Metformin and lung cancer

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