Diabetes Mellitus and Risk of Colorectal Cancer: A Meta-Analysis

Larsson, Susanna C.; Orsini, Nicola; Wolk, Alicja

doi:10.1093/jnci/dji375

Cited by 905 publications

(722 citation statements)

References 46 publications

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“…This is an important issue, as the epidemiologic studies that suggest anti-neoplastic activity of the drug were confined to patients with type II diabetes, where metformin lowers insulin levels. It is unclear if the effects of the drug on cancer end points in diabetic individuals, which have an increased cancer burden relative to non-diabetics (Larsson et al, 2005(Larsson et al, , 2007, are relevant to the general population.…”

Section: Discussionmentioning

confidence: 99%

Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo

et al. 2010

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Hypothesis-generating epidemiological research has suggested that cancer burden is reduced in diabetics treated with metformin and experimental work has raised questions regarding the role of direct adenosine monophosphate-activated protein kinase (AMPK)-mediated antineoplastic effects of metformin as compared with indirect effects attributable to reductions in circulating insulin levels in the host. We treated both tumor LKB1 expression and host diet as variables, and observed that metformin inhibited tumor growth and reduced insulin receptor activation in tumors of mice with diet-induced hyperinsulinemia, independent of tumor LKB1 expression. In the absence of hyperinsulinemia, metformin inhibited only the growth of tumors transfected with short hairpin RNA against LKB1, a finding attributable neither to an effect on host insulin level nor to activation of AMPK within the tumor. Further investigation in vitro showed that cells with reduced LKB1 expression are more sensitive to metformin-induced adenosine triphosphate depletion owing to impaired ability to activate LKB1-AMPK-dependent energy-conservation mechanisms. Thus, loss of function of LKB1 can accelerate proliferation in contexts where it functions as a tumor suppressor, but can also sensitize cells to metformin. These findings predict that any clinical utility of metformin or similar compounds in oncology will be restricted to subpopulations defined by host insulin levels and/or loss of function of LKB1.

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Section: Discussionmentioning

confidence: 99%

Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo

et al. 2010

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“…Increasing evidence has shown that diabetic patients have an increased risk of suffering CRC because of metabolic syndromes, such as insulin resistance, hyperinsulinaemia and hyperglycaemia (Kim 1998;Larsson et al 2005). Metformin, as the most widely used antidiabetic drug (Ben Sahra et al 2010), performs its therapeutic benefits through activating AMP-activated protein kinase, and have a potential role as anticancer drugs (Hardie 2007).…”

Section: Introductionmentioning

confidence: 99%

Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis

Nie

Zhu

2016

Pharmaceutical Biology

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Context: Diabetic patients have a higher risk of colorectal cancer (CRC). The role of metformin in CRC incidence among type 2 diabetes mellitus (T2DM) remains controversial. Objective: A meta-analysis was performed to evaluate the role of metformin treatment in the occurrence of CRC among T2DM patients. Methods: Search was performed throughout PubMed, Embase, Springer databases up to November 2014. The search terms were (biguanides or metformin) and (bowel or colon or rectal or colorectal) and (cancer or neoplasm or neoplasia). Relative risk (RR) and 95% confidence interval (CI) was pooled using randomeffects model or fixed-effect model basing on heterogeneity, which was calculated basing on Q statistics and v 2 test. In addition, subgroup analyses were performed according to region, study design and control treatment. Finally, publication bias was evaluated using Egger's regression test and trim and fill analysis. Results: A total of 11 studies, including eight cohort studies and three case-control studies, were enrolled in the meta-analysis. Obvious heterogeneity was noted, and a 25% lower CRC incidence was found among diabetic patients treated with metformin (pooled RR¼0.75, 95% CI: 0.66-0.86), using the random-effects model. Subgroup analyses showed that CRC incidence significantly reduced among T2DM in different regions, non-metformin treatment and cohort studies. Evidence supported significant publication for studies investigating from Egger's regression test. Conversely, no missing data were found using trim and fill analysis. Conclusion: In conclusion, the meta-analysis suggests metformin may reduce CRC incidence among diabetics, which is useful medical information for clinicians. ARTICLE HISTORY

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“…The excess risk for each cancer is~30% (colon),~50% (pancreas) and~20% (breast) [2][3][4]. Type 1 diabetes carries an excess cancer risk of~20%, but involves a different range of tumours [5].…”

Section: Introductionmentioning

confidence: 99%

Does diabetes therapy influence the risk of cancer?

2009

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Diabetes Mellitus and Risk of Colorectal Cancer: A Meta-Analysis

Abstract: Our findings strongly support a relationship between diabetes and increased risk of colon and rectal cancer in both women and men.

Cited by 905 publications

References 46 publications

Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo

Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo

Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis

Does diabetes therapy influence the risk of cancer?

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