Diabetes mellitus is a serious and growing health problem worldwide.1 Type 2 diabetes accounts for ∼90–95% of all diagnosed cases of diabetes2 and is characterized by insulin resistance and hyperinsulinemia in the early phases of the disease.3 It has been hypothesized that hyperinsulinemia may increase the risk of breast cancer through direct effects on breast tissue or indirectly by increasing circulating concentrations of estrogens, testosterone and insulin-like growth factors.4, 5 Thus, Type 2 diabetes may confer an excess risk of breast cancer. Diabetes has been related to an elevated risk of several cancers. Meta-analyses have indicated that diabetes is associated with a 1.2-fold increased risk of bladder cancer,6 1.3-fold increased risk of colorectal cancer,7 1.7-fold increased risk of pancreatic cancer8 and 2.5-fold increased risk of hepatocellular carcinoma.9 Wolf et al. combined the results of 4 case–control and 6 cohort studies and found that diabetes was associated with a 13 and 25% increased risk of breast cancer in case–control and cohort studies, respectively.10
The purpose of the present study was to summarize all available evidence from case–control and cohort studies on the relationship between diabetes and breast cancer incidence and mortality following the meta-analysis of observational studies in epidemiology (MOOSE) guidelines for meta-analyses of observational studies.11 This meta-analysis includes a total of 23 studies, thus providing more precise risk estimates than the previous analysis by Wolf et al.10 that was based on only 10 studies. In this study, we also examined whether the association between diabetes and breast cancer incidence differs according to various study characteristics and menopausal status.