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Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies

BMJ 2015; 350 doi: (Published 02 January 2015) Cite this as: BMJ 2015;350:g7607
  1. Konstantinos K Tsilidis, assistant professor12,
  2. John C Kasimis, PhD student1,
  3. David S Lopez, assistant professor3,
  4. Evangelia E Ntzani, assistant professor1,
  5. John P A Ioannidis, professor4
  1. 1Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, 45110, Greece
  2. 2Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  3. 3Division of Epidemiology, University of Texas School of Public Health, 1200 Pressler Street, Houston, TX 77030, USA
  4. 4Stanford Prevention Research Center, Department of Medicine, and Department of Health Research and Policy, Stanford University School of Medicine, and Department of Statistics, Stanford University School of Humanities and Sciences, 1265 Welch Rd., Stanford, CA, 94305, USA
  1. Correspondence to: K K Tsilidis, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Avenue, University Campus, Ioannina, Greece ktsilidi{at}
  • Accepted 27 October 2014


Objectives To summarise the evidence and evaluate the validity of the associations between type 2 diabetes and the risk of developing or dying from cancer.

Design An umbrella review of the evidence across meta-analyses of observational studies of type 2 diabetes with risk of developing or dying from any cancer.

Data sources PubMed, Embase, Cochrane database of systematic reviews, and manual screening of references.

Eligibility criteria Meta-analyses or systematic reviews of observational studies in humans that examined the association between type 2 diabetes and risk of developing or dying from cancer.

Results Eligible meta-analyses assessed associations between type 2 diabetes and risk of developing cancer in 20 sites and mortality for seven cancer sites. The summary random effects estimates were significant at P=0.05 in 20 meta-analyses (74%); and all reported increased risks of developing cancer for participants with versus without diabetes. Of the 27 meta-analyses, eventually only seven (26%) compiled evidence on more than 1000 cases, had significant summary associations at P≤0.001 for both random and fixed effects calculations, and had neither evidence of small study effects nor evidence for excess significance. Of those, only six (22%) did not have substantial heterogeneity (I2>75%), pertaining to associations between type 2 diabetes and risk of developing breast, cholangiocarcinoma (both intrahepatic and extrahepatic), colorectal, endometrial, and gallbladder cancer. The 95% prediction intervals excluded the null value for four of these associations (breast, intrahepatic cholangiocarcinoma, colorectal, and endometrial cancer).

Conclusions Though type 2 diabetes has been extensively studied in relation to risk of developing cancer and cancer mortality and strong claims of significance exist for most of the studied associations, only a minority of these associations have robust supporting evidence without hints of bias.


  • Contributors: All authors were involved in formulating the hypothesis and the design of the study protocol. The study hypothesis arose before inspection of the data. All authors had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. JCK and KKT carried out the search of the literature, data abstraction, data management, and statistical analysis. EEN and DSL verified several inputs of the final database of meta-analyses. KKT, JCK, and JPAI wrote the first draft; and all authors contributed to further drafts and approved the final version submitted. KKT and JCK contributed equally to this work. KKT and JPAI are guarantors.

  • Funding: This work was supported by the seventh framework programme of the European Union (PIEF-GA-2010-276017 to KKT and JPAI). The funding source detailed above had no role in the design, conduct, analysis, or reporting of the study. All authors carried out this research independently of the funding body.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Transparency declaration: The lead authors (the manuscript’s guarantors) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

  • Data sharing: No additional data available.

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