Additionally, while epidemiology has suggested a link between high IGF-I blood levels and increased cancer risk, a cancer-protective role of low IGF-I dose exposures, such as in IGF-I treated subjects affected by Laron syndrome (a genetic form of IGF-1 deficiency), has been more difficult to demonstrate given the fact that these subjects have cancer risk comparable to those exposed to higher IGF-I doses [reviewed by Werner and Laron [44]]. This evidence concerns the gene IGF1 and hyperinsulinemic hypoglycemia, familial, 4.