title: Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies.
abstract: OBJECTIVE
  To summarise the evidence and evaluate the validity of the associations between type 2 diabetes and the risk of developing or dying from cancer.
  
  
  METHODS
  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.
  
  
  METHODS
  PubMed, Embase, Cochrane database of systematic reviews, and manual screening of references.
  
  
  METHODS
  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 (I(2)>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.
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, 45110, Greece Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK ktsilidi@cc.uoi.gr.
authors.forename: Konstantinos K
authors.initials: KK
authors.lastname: Tsilidis
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, 45110, Greece.
authors.forename: John C
authors.initials: JC
authors.lastname: Kasimis
authors.affiliation: Division of Epidemiology, University of Texas School of Public Health, 1200 Pressler Street, Houston, TX 77030, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Lopez
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, 45110, Greece.
authors.forename: Evangelia E
authors.initials: EE
authors.lastname: Ntzani
authors.affiliation: Stanford 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.
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D048909:Diabetes Complications / Q000453:epidemiology* / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality; D015203:Reproducibility of Results; D012307:Risk Factors