Latest insights into the risk of cancer in diabetes

Abstract

A growing body of evidence from observational studies and meta-analyses of the data suggest that diabetes mellitus is associated with an increased risk of cancer. Meta-analyses have shown that diabetes increases the risks of total cancer, and of site-specific cancers of the breast, endometrium, bladder, liver, colorectum and pancreas, and that it decreases the risk of prostate cancer. Insulin resistance and secondary hyperinsulinemia is the most frequently proposed hypothesis, and hyperglycemia itself might promote carcinogenesis. In addition to several facets of lifestyle including obesity, smoking and lack of exercise, treatment for diabetes might affect the risk of cancer. For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden. The current insights underscore the need for clinical attention and better-designed studies of the complex interactions between diabetes and cancer.

Keywords: Cancer; Diabetes; Risk factors.

Figure 1

The insulin/insulin‐like growth factor‐1 (IGF‐1) receptor. Both the insulin receptor and the IGF receptor are encoded by single genes, which are processed into an α‐chain and β‐chain that remain linked by disulfide bonds. These α/β complexes can either homodimerize to form insulin receptors or IGF receptors, or heterodimerize to form hybrid receptors. Insulin binds preferentially to the insulin receptor, whereas IGF‐1 binds preferentially to the IGF‐1 and hybrid receptors. Although there is a great deal of overlap in their function, the insulin receptor is more closely linked with metabolic effects, whereas the hybrid receptor and IGF receptor are more closely linked with proliferation. Adapted from Biddinger et al.25 with permission.

Figure 2

Mechanisms of anti‐oncogenic effect of metformin. AMPK, adenosine 5′‐mono‐phosphate‐activated protein kinase; HER2, epithelial growth factor receptor 2; IGF, insulin‐like growth factor; IGF‐1R, insulin‐like growth factor 1; IR, insulin receptor; mTOR, mammalian target of rapamycin; PI3K, phosphinositide 3‐kinase; TSC2, tuberous sclerosis complex 2; VEGF, vascular endothelial growth factor. Adapted from Jalving et al.87 with permission.