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

Danielle M. Friedrichsen, Sarah Hawley, Jainfen Shu, Mariela Humphrey, Leah Sabacan, Lori Iwasaki, Ruth Etzioni, Elaine A. Ostrander, Janet L. Stanford

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)44-51
Number of pages8
JournalProstate
Volume65
Issue number1
DOIs
StatePublished - Sep 15 2005
Externally publishedYes

Keywords

  • IGF-I
  • IGFBP-3
  • Polymorphisms
  • Prostate cancer
  • Relative risk

ASJC Scopus subject areas

  • Oncology
  • Urology

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  • Cite this

    Friedrichsen, D. M., Hawley, S., Shu, J., Humphrey, M., Sabacan, L., Iwasaki, L., Etzioni, R., Ostrander, E. A., & Stanford, J. L. (2005). IGF-I and IGFBP-3 polymorphisms and risk of prostate cancer. Prostate, 65(1), 44-51. https://doi.org/10.1002/pros.20259