Skip to main content
SpringerLink
Log in

Polymorphic CA repeats in the IGF-I gene and breast cancer

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Insulin-like growth factor (IGF)-I is a potent mitogen for breast cancer cells and may play a role in the disease. Although the involvement of IGF-I phenotype in breast cancer has been studied extensively, little is known about IGF-I genotype in relation to the disease. The IGF-I gene contains a polymorphic region composed of multiple cytosine-adenine dinucleotides (CA repeats). Studies of other genes indicate that the CA-repeat region in the promoter of a gene may affect transcription activity and that the length of the repeat is inversely correlated with transactivation. To examine if the IGF-I polymorphism is associated with breast cancer, we compared the length of CA repeats in the IGF-I gene between 53 breast cancer patients and 53 controls. Genomic DNA extracted from peripheral blood was used to determine the number of CA repeats through PCR amplification and DNA sequencing. Associations between CA repeats and breast cancer were assessed using unconditional logistic regression analysis. The results showed that the median number of CA repeats was 19, ranging from 15 to 23, and that compared to women without 19 CA repeats, women with 19 CA repeats were more likely to be breast cancer patients (OR = 2.87, 95%CI: 1.16–7.06) after adjusting for age, race, menopausal status, age at menopause, and alcohol use. The study also suggested possible synergistic interplay between IGF-I genotype and phenotype as women with 19 CA repeats and high plasma IGF-I had a much higher odds ratio for breast cancer (OR = 5.12, 95%CI: 1.42–18.5) than those with only one of the conditions. If our observations can be confirmed in larger studies, the findings will provide further evidence to support the role of IGF-I in breast cancer and the link between genetic polymorphism and cancer susceptibility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Jones JI, Clemmons DR: Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16: 3-34, 1995

    Google Scholar 

  2. LeRoith D, Werner H, Beitner-Johnson D, Roberts CT: Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 16: 143-613, 1995

    Google Scholar 

  3. Kelley KM, Oh Y, Gargosky SE, Gucev Z, Matsumoto T, Hwa V NgL, Simpson DM, Rosenfeld RG: Insulin-like growth factor-binding proteins (IGFBPs) and their regulatory dynamics. Int J Biochem Cell Biol 28: 619-637, 1996

    Google Scholar 

  4. Macaulay VM: Insulin-like growth factors and cancer. Br J Cancer 65: 311-320, 1992

    Google Scholar 

  5. LeRoith D, Baserga R, Helman L, Roberts CT: Insulin-like growth factors and cancer. Ann Int Med 122: 54-59, 1995

    Google Scholar 

  6. Pollak MN: Endocrine effects of IGF-I on normal and transformed breast epithelial cells: potential relevance to strategies for breast cancer treatment and prevention. Breast Cancer Res Treat 47: 209-217, 1998

    Google Scholar 

  7. Dunn SE, Hardman RA, Kari FW, Barrett JC: Insulin-like growth factor 1 (IGF-1) alters drug sensitivity of HBL100 human breast cancer cells by inhibition of apoptosis induced by diverse anticancer drug. Cancer Res 57: 2687-2693, 1997

    Google Scholar 

  8. Rasmussen AA, Cullen KJ: Paracrine/autocrine regulation of breast cancer by the insulin-like growth factors. Breast Cancer Res Treat 47: 219-233, 1998

    Google Scholar 

  9. Lee AV, Jackson JG, Gooch JL, Hilsenbeck SG, Coronado-Heinsohn E, Osborne CK, Yee D: Enhancement of insulinlike growth factor signaling in human breast cancer: estrogen regulation of insulin receptor substrate-1 expression in vitro and in vivo. Mol Endocrinol 13: 787-796, 1999

    Google Scholar 

  10. Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, Rosner B, Speizer FE, Pollak M: Circulating concentrations of insulin-like growth factor-1 and risk of breast cancer. Lancet 351: 1393-1396, 1998

    Google Scholar 

  11. Bruning PF, van Doorn J, Bonfrer MG, Van Noord PAH, Korse CM, Linders TC: Insulin-like growth-factor binding prote in 3 is decreased in early-stage operable pre-menopausal breast cancer. Int J Cancer 62: 266-270, 1995

    Google Scholar 

  12. Bohlke K, Cramer DW, Trichopoulos D, Mantzoros CS: Insulin-like growth factor-1 in relation to premenopausal ductal carcinoma in situ of the breast. Epidemiol 9: 570-573, 1998

    Google Scholar 

  13. Byrne C, Colditz GA, Willett WC, Speizer FE, Pollak M, Hankinson SE: Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density. Cancer Res 60: 3744-3748, 2000

    Google Scholar 

  14. D'Ercole AJ: Insulin-like growth factors and their receptors in growth. Endocrinol Metab Clin North Am 25: 573-590, 1996

    Google Scholar 

  15. Rotwein P, Pollock KM, Didier DK, Krivi GG: Organization and sequence of the human insulin-like growth factor I gene. Alternative RNA processing produces two insulin-like growth factor I precursor peptides. J Biol Chem 261: 4828-4832, 1986

    Google Scholar 

  16. Rosen CJ, Kurland ES, Vereault D, Adler RA, Rackoff PJ, Craig WY, Witte S, Rogers J, Bilezikian JP: Association between serum insulin-like growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene: implications for genetic studies of bone mineral density. J Clin Endocrinol Metab 83: 2286-2290, 1998

    Google Scholar 

  17. Miyao M, Hosoi T, Inoue S, Hoshino S, Shiraki M, Orimo H, Ouchi Y: Polymorphism of insulin-like growth factor I gene and bone mineral density. Calcif Tissue Int 63: 306-311, 1998

    Google Scholar 

  18. Tae HJ, Luo X, Kim KH: Roles of CCAAT/enhancer-binding protein and its binding site on repression and derepression of acetyl-CoA carboxylase gene. J Biol Chem 269: 10475-10484, 1994

    Google Scholar 

  19. Gebhardt F, Zanker KS, Brandt B: Modulation of epidermal growth factor receptor gene transcription by a polymorphic dinucleotide repeat in intron 1. J Biol Chem 274: 13176-13180, 1999

    Google Scholar 

  20. Kato I, Eastham J, Li B, Smith M, Yu H. Functional significance of the polymorphic CA repeats in the insulin-like growth factor-I gene. (submitted for publication)

  21. Cohen P: Serum insulin-like growth factor-I levels and prostate cancer risk-interpreting the evidence. J Natl Cancer Inst 90: 876-879, 1998

    Google Scholar 

  22. Burroughs KD, Dunn SE, Barrett JC, Taylor JA: Insulin-like growth factor-I: a key regulator of human cancer risk? J Natl Cancer Inst 91: 579-581, 1999

    Google Scholar 

  23. Takacs I, Koller DL, Peacock M, Christian JC, Hui SL, Conneally PM, Johnson CC Jr, Foroud T, Econs MJ: Sibling pair linkage and association studies between bone mineral density and the insulin-like growth factor I gene locus. J Clin Endocrinol Metab 84: 4467-4471, 1999

    Google Scholar 

  24. Sun G, Gagnon J, Chagnon YC, Perusse L, Despres JP, Leon AS, Wilmore JH, Skinner JS, Borecki I, Rao DC, Bouchard C: Association and linkage between an insulin-like growth factor-1 gene polymorphism and fat free mass in the HERITAGE family study. Int J Obes Relat Metab Disord 23: 929-935, 1999

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Feist-Weiller Cancer Center and Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, LA, USA

    Herbert Yu, Mylinh Smith, Runhua Shi, Hans (J) Berkel & Ikuko Kato

  2. Department of Surgery, Louisiana State University Health Sciences Center, Shreveport, LA, USA

    Benjamin D.L. Li

  3. Department of Epidemiology, Karmanos Cancer Institute and Department of Pathology, Wayne State University, Detroit, MI, USA

    Ikuko Kato

Authors
  1. Herbert Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Benjamin D.L. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mylinh Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Runhua Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hans (J) Berkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ikuko Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yu, H., Li, B.D., Smith, M. et al. Polymorphic CA repeats in the IGF-I gene and breast cancer. Breast Cancer Res Treat 70, 117–122 (2001). https://doi.org/10.1023/A:1012947027213

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1012947027213

Search

Navigation