Breast Cancer Research and Treatment

, Volume 92, Issue 2, pp 133–140 | Cite as

Polymorphisms in the IGF-1 and IGFBP3 promoter and the risk of breast cancer

  • Kerstin Wagner
  • Kari Hemminki
  • Elisabeth Israelsson
  • Ewa Grzybowska
  • Magnus Söderberg
  • Jolanta Pamula
  • Wioletta Pekala
  • Helena Zientek
  • Danuta Mielzynska
  • Ewa Siwinska
  • Asta Försti


Binding of IGF-1 to the type I IGF receptor starts a signalling cascade that plays an important role in regulating cell proliferation, differentiation and apoptosis. The interaction between the IGF-1 and its receptor is mainly regulated by a binding protein, IGFBP3. We studied a CA repeat polymorphism 969 bp upstream of the transcription start site in the IGF-1 gene and an A-202C polymorphism in the IGFBP3 gene and tested their association with breast cancer risk using four case–control series with a total of 787 cases and 900 controls. We did not find any association between the breast cancer risk and the IGF-1 repeat length (19 versus non-19) or the IGFBP3 A-202C polymorphism in the postmenopausal breast cancer series or in women diagnosed for breast cancer under the age of 50. In the familial breast cancer series we observed a non-significantly increased odds-ratio (OR) in homozygotes for the non-19 alleles of the IGF-1 gene (OR 1.51, 95% CI 0.96–2.39, p=0.07). Similarly, in the familial breast cancer series we detected an increased frequency of the IGFBP3 −202C allele carriers (OR 1.50, 95% CI 1.05–2.14, p=0.03). The association was stronger in individuals homozygous for these alleles (OR 3.76, 95% CI 1.44–9.81, p=0.006). Thus, the polymorphisms in the IGF-1 and IGFBP3 genes associated with an increased risk of breast cancer in familial cases carrying the variant alleles.

Key words

breast cancer case–control study IGF-1 IGFBP3 polymorphism 



95% confidence interval


Hardy–Weinberg equilibrium


insulin-like growth factor


insulin-like growth factor binding protein


insulin-like growth factor-1/2 receptor




restriction fragment length polymorphism


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Copyright information

© Springer 2005

Authors and Affiliations

  • Kerstin Wagner
    • 1
  • Kari Hemminki
    • 1
    • 2
  • Elisabeth Israelsson
    • 2
  • Ewa Grzybowska
    • 3
  • Magnus Söderberg
    • 4
  • Jolanta Pamula
    • 3
  • Wioletta Pekala
    • 3
  • Helena Zientek
    • 3
  • Danuta Mielzynska
    • 5
  • Ewa Siwinska
    • 5
  • Asta Försti
    • 1
    • 2
  1. 1.Division of Molecular Genetic Epidemiology C050German Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.Department of Biosciences at NovumKarolinska InstituteHuddingeSweden
  3. 3.Department of Tumor Biology, Centre of OncologyMaria Sklodowska-Curie InstituteGliwicePoland
  4. 4.Department of PathologyHuddinge HospitalHuddingeSweden
  5. 5.Department of Genetic ToxicologyInstitute of Occupational Medicine and Environmental HealthSosnowiecPoland

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