Breast Cancer Research and Treatment

, Volume 92, Issue 2, pp 133–140

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

Authors

    • Division of Molecular Genetic Epidemiology C050German Cancer Research Center (DKFZ)
  • Kari Hemminki
    • Division of Molecular Genetic Epidemiology C050German Cancer Research Center (DKFZ)
    • Department of Biosciences at NovumKarolinska Institute
  • Elisabeth Israelsson
    • Department of Biosciences at NovumKarolinska Institute
  • Ewa Grzybowska
    • Department of Tumor Biology, Centre of OncologyMaria Sklodowska-Curie Institute
  • Magnus Söderberg
    • Department of PathologyHuddinge Hospital
  • Jolanta Pamula
    • Department of Tumor Biology, Centre of OncologyMaria Sklodowska-Curie Institute
  • Wioletta Pekala
    • Department of Tumor Biology, Centre of OncologyMaria Sklodowska-Curie Institute
  • Helena Zientek
    • Department of Tumor Biology, Centre of OncologyMaria Sklodowska-Curie Institute
  • Danuta Mielzynska
    • Department of Genetic ToxicologyInstitute of Occupational Medicine and Environmental Health
  • Ewa Siwinska
    • Department of Genetic ToxicologyInstitute of Occupational Medicine and Environmental Health
  • Asta Försti
    • Division of Molecular Genetic Epidemiology C050German Cancer Research Center (DKFZ)
    • Department of Biosciences at NovumKarolinska Institute
Report

DOI: 10.1007/s10549-005-2417-x

Cite this article as:
Wagner, K., Hemminki, K., Israelsson, E. et al. Breast Cancer Res Treat (2005) 92: 133. doi:10.1007/s10549-005-2417-x

Summary

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 cancercase–control studyIGF-1IGFBP3polymorphism

Abbreviations

CI

95% confidence interval

HWE

Hardy–Weinberg equilibrium

IGF-1

insulin-like growth factor

IGFBP3

insulin-like growth factor binding protein

IGF-1R/IGF-2R

insulin-like growth factor-1/2 receptor

OR

odds-ratio

RFLP

restriction fragment length polymorphism

Copyright information

© Springer 2005