However, there is also evidence that does not support a causal association between serum IGF-I (or IGFBP-3, discussed below) and the risk of PCa (Woodson et al., 2003), and it was hypothesized that high-grade PCas are more autonomous and less sensitive to the action of IGF-I than low-grade cancers (Nimptsch et al., 2011). Here, IGF1 is linked to cancer.