Metformin does not alter the risk of lung cancer: A case-control analysis

Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Switzerland
Lung cancer (Amsterdam, Netherlands) (Impact Factor: 3.96). 09/2012; 78(2):133-7. DOI: 10.1016/j.lungcan.2012.08.010
Source: PubMed


Metformin use has been linked to a decreased cancer risk. We explored the association between use of metformin or other antidiabetic drugs and the risk of lung cancer.
We assessed the association between metformin, and other antidiabetic drugs and lung cancer using a case-control analysis in the UK-based General Practice Research Database (GPRD). Cases were people with an incident diagnosis of lung cancer. Up to 6 controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD. The contribution of potential confounders including tuberculosis, chronic obstructive pulmonary disease (COPD), diabetes mellitus, and co-morbid conditions to diabetes was evaluated in univariate models, and final results were adjusted for BMI and smoking.
Long-term use (≥40 prescriptions) of metformin was not associated with an altered risk of lung cancer (adj. OR 1.21, 95% CI 0.97-1.50. Long-term use of sulfonylureas was linked to a marginally decreased risk of lung cancer (adj. OR 0.74, 95% CI 0.60-0.90. This risk decrease was observed in men (adj. OR 0.64, 95% CI 0.50-0.83) but not in women (adj. OR 0.97, 95% CI 0.69-1.37) and this risk decrease was not statistically significant in an analysis restricted to diabetic patients only (adj. OR. 0.82, 95% CI 0.65-1.02). Long-term use of insulin was associated with a slightly increased risk of lung cancer (adj. OR 1.33, 95% CI 1.04-1.71); however, no consistent trend across duration strata was observed.
Metformin did not decrease the risk of lung cancer.

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    • "In contrast, others have shown a non-significant protective effect on lung cancer [12] [13]. Likewise, insulin and insulin secretagogues have been shown to be related to higher lung cancer incidence and cancer-related mortality [14] [15]. But others have shown no harmful or even protective effects [16] [17]. "
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    ABSTRACT: Background Accumulating evidence suggests that hypoglycaemic agents influence lung cancer risk in patients with diabetes. It remains to be fully elucidated whether conventional hypoglycaemic agents (metformin, sulfonylureas, thiazolidinediones [TZDs] or insulin) affect lung cancer incidence in patients with diabetes. Methods We performed a meta-analysis using EMBASE, MEDLINE and Web of Science to search randomised controlled trials (RCTs), cohort studies, and case-control studies published up to October 2013 that assessed the effects of metformin, sulfonylurea, TZDs or insulin on lung cancer risk in subjects with diabetes. Fixed and random effects meta-analysis models were used, and the effect size was expressed as a summary odds ratio (OR) with 95% confidence intervals (CI). The Grades of Research, Assessment, Development and Evaluation (GRADE) approach was applied to define the quality of the evidence. Results Analysis of 15 studies (11 cohort studies, 2 case-control studies, and 2 RCTs) showed that metformin use was associated with a 15% reduction in risk of lung cancer (OR 0.85, 95% CI 0.77 to 0.92), but this finding was not supported by sub-analysis of smoking-adjusted studies (OR 0.84, 95% CI 0.61 to 1.06). Moreover, sulfonylurea or TZDs use was not associated with increased or decreased lung cancer risk, respectively (OR 1.10, 95% CI 0.93 to 1.26), (OR 0.86, 95% CI 0.70 to 1.02). Higher lung cancer risk was related to insulin (OR 1.23, 95% CI 1.10 to 1.35). However, all data from RCTs failed to demonstrate a statistically significant effect. Conclusions This analysis demonstrated that metformin use may reduce lung cancer risk in patients with diabetes but not in a smoking-adjusted subgroup and that insulin use may be associated with an increased lung cancer risk in subjects with diabetes.
    PLoS ONE 06/2014; 9(6):e99577. DOI:10.1371/journal.pone.0099577 · 3.23 Impact Factor
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    • "Interestingly, there is a conflicting report regarding the potential role of metformin and cancer. Bodmer and colleagues found that use of metformin was not associated with a decreased risk of colorectal cancer and metformin also did not alter the risk of lung cancer [10], [24]. It is also reported that there was no statistically significant association between metformin exposure and disseminated colorectal cancer at diagnosis [25]. "
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    ABSTRACT: Colorectal cancer (CRC) is still the third most common cancer and the second most common causes of cancer-related death around the world. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been shown to have a suppressive effect on CRC risk and mortality, but not all laboratory studies suggest that metformin has antineoplastic activity. Here, we investigated the effect of metformin and AMPK activator AICAR on CRC cells proliferation. As a result, metformin did not inhibit cell proliferation or induce apoptosis for CRC cell lines in vitro and in vivo. Different from metformin, AICAR emerged antitumor activity and sensitized anticancer effect of 5-FU on CRC cells in vitro and in vivo. In further analysis, we show that AMPK activation may be a key molecular mechanism for the additive effect of AICAR. Taken together, our results suggest that metformin has not antineoplastic activity for CRC cells as a single agent but AMPK activator AICAR can induce apoptosis and enhance the cytotoxic effect of 5-FU through AMPK activation.
    PLoS ONE 05/2014; 9(5):e97781. DOI:10.1371/journal.pone.0097781 · 3.23 Impact Factor
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    • "Evidence shows that metformin also inhibits PI3K/AKT/mTOR signaling. As mentioned above, observational studies have found a decreased incidence of lung cancer in diabetics treated with metformin compared with other agents [105,106], although not all studies confirm this observation [107,108]. "
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    ABSTRACT: Decreasing the risk of lung cancer, or preventing its development in high-risk individuals, would have a huge impact on public health. The most effective means to decrease lung cancer incidence is to eliminate exposure to carcinogens. However, with recent advances in the understanding of pulmonary carcinogenesis and the identification of intermediate biomarkers, the prospects for the field of chemoprevention research have improved dramatically. Here we review the most recent research in lung cancer chemoprevention-focusing on those agents that have been investigated in human clinical trials. These agents fall into three major categories. First, oxidative stress plays an important role in pulmonary carcinogenesis; and therefore, antioxidants (including vitamins, selenium, green tea extracts, and isothiocyanates) may be particularly effective in preventing the development of lung cancer. Second, inflammation is increasingly accepted as a crucial factor in carcinogenesis, and many investigators have focused on anti-inflammatory agents, such as glucocorticoids, NSAIDs, statins, and PPARγ agonists. Finally, the PI3K/AKT/mTOR pathway is recognized to play a central role in tobacco-induced carcinogenesis, and inhibitors of this pathway, including myoinositol and metformin, are promising agents for lung cancer prevention. Successful chemoprevention will likely require targeting of multiple pathways to carcinogenesis-both to minimize toxicity and maximize efficacy.
    Cancers 03/2013; 5(1):131-48. DOI:10.3390/cancers5010131
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