Insulin-like growth factor axis and exercise  

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The most compelling emerging evidence supports the idea that physical activity might exert its beneficial effect on cancer via a protein called insulin-like growth factor (IGF) axis. A number of large studies involving patients with established cancer have shown higher blood levels of insulin-like growth factor 1 (IGF-1) and another protein called C peptide in patients with cancer, particularly bowel cancer. The benefits of lowering IGF-1 may be linked to its central role in the growth regulation processes. The main stimulus for IGF-1 production comes from growth hormone.  This stimulatory effect of growth hormone is modulated by insulin, which increases growth hormone receptor levels and in turn IGF-1. Early studies have shown that after binding to its receptors, which are found on normal colonic mucosal cells as well as colon cancer cells, IGF-1 can stimulate cells to grow faster and in an uncontrolled way (proliferation), inhibit the normal life cycle i.e. let cells not to die of old age when they ought to (apoptosis).

Other studies have also showed that IGF-1 binding triggers the formation of new blood vessels essential for tumours to grow rapidly (angiogenesis). In the circulation, as over 90% of IGF-1 is bound to a protein called IGFRBP-3 (insulin-like Growth Factor Binding Protein 3), binding inhibits the action of IGF-1 by limiting the availability of free hormone.  This explains the finding that, higher blood levels of IGFBP-3 are associated with lower levels IGFR-1. Conversely, patients with lower levels IGFBP-3 are associated with a worse outcome and higher free levels of IGFR-1.

People who exercise regularly have been convincingly been shown to have lower IGF-1 and higher IGFBP-3 levels. The most convincing evidence that this correlate with cancer outcomes comes from a study of 41,528 people aged between 27 and 75 years with colorectal cancer. Patients recruited between 1990 and 1994 had their exercise activity recorded along with regular blood tests. Confirming previous studies, lower IGF-1 and higher IGFBP-3 levels significantly correlated with higher exercise activity. More excitingly these factors, at diagnosis were associated with lower chance of the cancer returning and a higher chance of being alive at 5 years.  A similar study conducted by the Melbourne collaborative cohort study group looked at exercise patterns after diagnosis and found the same relationship confirming the intriguing role exercise IGF-1 has in cancer recurrence mechanism.

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