No association between genetic polymorphisms in IGF-I and IGFBP-3 and prostate cancer.

High levels of circulating insulin-like growth factor-I (IGF-I), or IGF-I in relation to IGF binding protein-3 (IGFBP-3), have been associated with an increased risk of prostate cancer (CaP) and other common epithelial cell malignancies (1). Twin studies estimate that 38% of the interindividual variability of IGF-I and up to 60% of that of IGFBP-3 are attributable to genetic factors (2). Recent work has identified a highly polymorphic cytosine-adenosine (CA)n dinucleotide repeat in the promoter region of the IGF-I gene and a single nucleotide polymorphism in the promoter region ( 202) of the IGFBP-3 gene (3, 4). The IGF-I (CA)n repeat sequence is 1 kb upstream of the IGF-I transcription start site and contains specific regulatory elements (3, 4). Hence, we hypothesized that the length of (CA)n repeats might affect the transcription activity of the IGF-I gene, resulting in variable levels of IGF-I expression and affecting CaP risk or aggressiveness. Moreover, because previous studies have shown that the IGFBP-3 ( 202) polymorphism is functional and is associated with circulating levels of IGFBP-3 (5), we anticipated that this variant might impact CaP risk as well.