Metabolic disorders and cancer

Epidemiological studies clearly indicate that obesity and type 2 diabetes predispose individuals to a higher risk of developing cancer. Although the precise mechanism underlying this observation is unknown, insulin resistance, metabolic imbalance and inflammatory cytokines are thought to be involved.

In the EU-funded DIABESITY (Obesity, type 2 diabetes and the increased risk of cancer and cancer-related mortality; the study of molecular mechanisms and potential therapeutic modalities) project, scientists wished to investigate if endogenous hyperinsulinemia influenced mammary tumour development. Consortium members had replicated the increased association of obesity and type 2 diabetes with breast cancer in a previous project using animal models.

Researchers utilised a hyperinsulinemic mouse model and showed that mammary tumours grew more rapidly compared to control mice. A similar observation was noted with lung metastases. They noted that breast cancer growth was mediated through the insulin receptor and genes involved in growth, metastases and anti-apoptosis were expressed in tumours. Similar experiments in dyslipidemic ApoE knockout mice revealed that abnormal lipid metabolism and high blood cholesterol levels can enhance breast cancer formation.

Collectively, the DIABESITY study demonstrated at the preclinical level that predisposition to cancer is linked to metabolic defects. This specific causality is expected to help towards the design of new therapeutic agents for obese and diabetic patients with cancer.