title: Insulin therapy and the risk of colorectal cancer in patients with type 2 diabetes: a meta-analysis of observational studies.
abstract: OBJECTIVE
  Several epidemiological studies have reported inconsistent associations between insulin therapy and the risk of colorectal cancer (CRC) in patients with type 2 diabetes mellitus. We performed this meta-analysis of observational studies to evaluate the effect of insulin therapy on the risk of CRC.
  
  
  METHODS
  We carried out a systematic search of PubMed, Embase and the Cochrane Library Central database between January 1966 and August 2013. Fixed-effects and random-effects models were used to estimate the pooled relative risk (RR) and corresponding 95% confidence interval (CI).
  
  
  RESULTS
  A total of 12 epidemiological studies were included in the present meta-analysis, involving a total of 7947 CRC cases and 491 384 participants. There was significant heterogeneity among the studies, but no publication bias. Insulin therapy significantly increased the risk of CRC [RR = 1.69, 95% CI (1.25, 2.27)]. When the various studies were stratified by study design, we found that insulin use was associated with a statistically significant 115% higher risk of CRC among case-control studies [RR = 2.15, 95% CI (1.41, 3.26)], but not among cohort studies [RR = 1.25, 95% CI (0.95, 1.65)]. Furthermore, a significant association was noted among studies conducted in USA [RR = 1.73, 95% CI (1.15, 2.60)] and Asia [RR = 2.55, 95% CI (2.14, 3.04)], but not in Europe [RR = 1.20, 95% CI (0.92, 1.57)].
  
  
  CONCLUSIONS
  The present meta-analysis suggests that insulin therapy may increase the risk of CRC. More prospective cohort studies with longer follow-up durations are warranted to confirm this association. Furthermore, future studies should report results stratified by gender and race and should adjust the results by more confounders.
authors.affiliation: Department of Medical Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Wu-jie
authors.initials: WJ
authors.lastname: Bu
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.forename: Dan-yi
authors.initials: DY
authors.lastname: Zhao
authors.forename: Bing
authors.initials: B
authors.lastname: Guo
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
mesh_terms: D015179:Colorectal Neoplasms / Q000139:chemically induced*; D003627:Data Interpretation, Statistical; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D064887:Observational Studies as Topic; D012306:Risk
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: colorectal cancer; epidemiology; insulin; meta-analysis
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