IGF-I and IGFBP-3 polymorphisms and risk of prostate cancer

Prostate. 2005 Sep 15;65(1):44-51. doi: 10.1002/pros.20259.


Background: Insulin-like growth factor-I (IGF-I) is a potent mitogen for both normal and malignant prostate epithelial cells. The majority of circulating IGF-I is bound in a complex with IGF binding protein-3 (IGFBP-3), which in turn limits IGF-I bioavailability. Multiple studies suggest that higher IGF-I and/or lower IGFBP-3 serum levels are positively associated with prostate cancer risk. Several polymorphisms within the IGF-I and IGFBP-3 coding regions have been associated with increased serum protein levels.

Methods: To ascertain the potential relationship between serum levels and polymorphism, and prostate cancer risk, we investigated the role of two polymorphisms the IGF-I cytosine-adenosine (CA)-repeat and the IGFBP-3 Ala32Gly, and prostate cancer in a population-based, case-control, study of middle-aged men.

Results: We found no significant association between the IGFBP-3 Ala32Gly polymorphism and prostate cancer risk, even though the presence of at least one Gly allele did correlate with increased serum levels of IGFBP-3. For IGF-I, more controls (42%) than cases (38%) were homozygous for 19-CA-repeats (odds ratio, OR = 0.85; 95% confidence interval (CI) = 0.66-1.09). After stratifying by disease characteristics, 19-CA-repeat homozygous men displayed a decreased risk of low-grade disease (OR = 0.50; 95% CI = 0.27-0.93), but no associations were observed with more aggressive features of disease. Additionally, there was no correlation between mean serum IGF-I protein levels and IGF-I genotype in controls.

Conclusions: Further evaluation of the IGF-I CA-repeat polymorphism and prostate cancer is necessary to determine if the modest risk reduction associated with the 19-CA-repeat homozygous state is observed in other study populations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Case-Control Studies
  • Dinucleotide Repeats
  • Genotype
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor Binding Protein 3 / genetics*
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / etiology
  • Prostatic Neoplasms / genetics*
  • Risk


  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I