Systematic review and meta-analysis of insulin therapy and risk of cancer

Abstract

Recent epidemiological studies suggest that treatment with insulin may promote cancer growth. The present systematic review and meta-analysis of published observational studies was conducted to assess the risk of cancer during treatment with insulin. A search of online database through January 2011 was performed and examined the reference lists of pertinent articles, limited to observational studies in humans. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Fifteen studies (five case-control and ten cohort studies) were included, with 562,043 participants and 14,085 cases of cancer. Insulin treatment was associated with an increased risk of overall cancer [summary RR (95% CI)=1.39 (1.14, 1.70)]. Summary RR (9% CI) for case-control studies was 1.83 (0.99, 3.38), whereas RR for cohort studies was 1.28 (1.03, 1.59). These results were consistent between studies conducted in the USA and in Europe. For studies that included combined type 1 and 2 diabetes, the summary estimate was stronger than studies including only type 2 diabetes mellitus. The association between insulin treatment and cancer was stronger for pancreatic cancer [summary RR (95% CI)=4.78 (3.12, 7.32)] than for colorectal cancer [1.50 (1.08, 2.08)]. Insulin treatment was not associated with breast, prostate, and hepatocelluar cancer, and their effect estimates were not statistically significant. Our findings support an association between insulin use and increased risk of overall, pancreatic, and colorectal cancer.

Fig. 1

Association between insulin use and cancer risk. RR relative risk, CI confidence interval. Square study-specific RR estimate (size of the square reflects the study specific statistical weight, i.e., the inverse of variance); horizontal line 95 % CI, diamond summary RR estimate and its corresponding 95 % CI. All statistical tests were two-sided. Statistical heterogeneity between studies was assessed with I ² test

Fig. 2

Association between insulin use and cancer risk in cohort and case–control studies. RR relative risk, CI confidence interval. Square study-specific RR estimate (size of the square reflects the study specific statistical weight, i.e., the inverse of variance); horizontal line 95 % CI; diamond summary RR estimate and its corresponding 95 % CI. All statistical tests were two-sided. Statistical heterogeneity between studies was assessed with I ² test