How does low IGF-I bioactivity decrease cancer risk?

. IGF-I (insulin-like growth factor-I) is often referred to as “the universal cancer promoter”.  This reflects the fact that a high proportion of the tissues most likely to give rise to cancer are sensitive to its growth factor activity.   In the many body tissues that are responsive to it, high IGF-I activity can accelerate the onset of cancer by increasing the rate at which mutations occur in DNA, and also by blocking a protective process whereby pre-cancerous cells commit suicide to protect the body from cancer.  Conversely, relatively low IGF-I bioactivity is protective in these respects. 

IGF-I can increase cancer risk in tissues responsive to its growth factor activity by at least two interactive mechanisms.  Firstly, by boosting the rate at which stem cells multiply, it increases the rate at which mutations accumulate in these cells.  Whenever a cell divides, it needs to correctly replicate the base pair code of its entire DNA.  There are billions of base pairs in the DNA of a cell, and cells make errors, just like humans do.  Fortunately, our cells have reasonably efficient error detection and correction mechanisms, but these aren’t perfect either.  So after each cell division, the daughter cells will harbor errors in the DNA code known as mutations.   Most these mutations are innocuous.  Some of them may kill the cell – which usually isn’t a major problem, as we have billions of other cells.  But some of the mutations may lead to changes in the quantity or structure of key cellular proteins that regulate cell multiplication and behavior.  When a stem cell accumulates too many of the wrong types of mutations, its growth regulation may become seriously impaired, such that it multiplies and spreads without regard for the health of the host; that’s known as having cancer.  The ability of IGF-I to accelerate the accumulation of mutations in tissues sensitivity to its activity is therefore a key way in which unnecessarily high IGF-I activity elevates cancer risk.

High IGF-I activity may also encourage mutations in its target tissues by suppressing the production of antioxidant enzymes that protect DNA from oxidative stress.  The production of a number of these enzymes is boosted by a factor known as FOXO3a, whose activity is inhibited by IGF-I as well as insulin. 

Secondly, IGF-I can increase cancer risk by inhibiting a potentially protective process known as “apoptosis”.   For reasons that are still unclear, when stem cells are accumulating mutations which impair their growth regulation, they often have a way of detecting this, and, in response, they “commit suicide” in a regulated way known as apoptosis.  This is highly protective for the host, since a precancerous cell that has killed itself can’t go on to give rise to a cancer.  But if precancerous stem cells are sensitive to IGF-I, IGF-I activity tends to “veto” this apoptotic response.  As a result, a precancerous cell may be more prone to survive.  And if it or its progeny go on to acquire one or two more key mutations, a full fledged cancer may result.

In brief, high IGF-I activity increases cancer risk by accelerating the rate at which stem cells accumulate mutations, and by vetoing the protective process whereby precancerous mutated stem cells commit suicide.  Conversely, measures which tend to decrease IGF-I’s bioactivity – such as calorie restriction, good insulin sensitivity, and essential amino acid restriction (a feature of many vegan diets) – tend to lower cancer risk.

← Back to Frequently Asked Questions