Prostate Cancer Risk in Relation to Selected Genetic Polymorphisms in Insulin-like Growth Factor-I, Insulin-like Growth Factor Binding Protein-3, and Insulin-like Growth Factor-I Receptor

Abstract

We conducted a nested case-control study within a cohort of elderly Americans to examine the role of the insulin-like growth factor (IGF) signaling pathway in prostate cancer etiology. The distribution of genotypes of IGF-I (CA)n, IGF binding protein-3 (IGFBP-3) A-202C, and of the 2-bp deletion and (AGG)n polymorphisms in IGF-I receptor (IGF-IR) was compared between men with prostate cancer (n = 213) and equal number of controls matched on year of blood draw, survival until the date of diagnosis, race, and age. Among controls, the number of CA repeats in IGF-I was not correlated to any appreciable degree with plasma IGF-I concentration, whereas the IGFBP-3 CC genotype was associated with a relatively low level of plasma IGFBP-3. There was no association between prostate cancer risk and the number of CA repeats in IGF-I, IGFBP-3 genotype, or the presence of the 2-bp deletion in IGF-IR. There was a small increased risk among men who did not carry two copies of the (AGG)7 allele of IGF-IR. These results add to the evidence that the number of IGF-I CA repeats is not associated with prostate cancer risk. Our observation that men who do not carry two copies of the IGF-IR (AGG)7 allele are at increased risk of prostate cancer merits further investigation.