Skip to main content

Advertisement

SpringerLink
Log in

A high risk of occurrence of sporadic breast cancer in individuals with the 104NN polymorphism of the COL18A1 gene

  • Letter to the Editor
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

We investigated the influence of the polymorphism D104N of the COL18A1 gene, encoding endostatin, on the occurrence of sporadic breast cancer in 181 patients and 448 controls. The homozygous 104NN polymorphism was found in five patients but was absent in controls (2.8% vs 0.0%; P = 0.002). Individuals with this genotype had a significantly increased risk for disease. Our results suggest, for the first time, that the homozygous 104NN polymorphism, even at low frequency, constitutes an important inherited determinant of the disease.

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.

Institutional subscriptions

References

  1. Nakamura Y, Yasuoka H, Tsujimoto M, Imabun S, Nakahara M, Nakao K, Nakamura M, Mori I, Kakudo K (2005) Lymph vessel density correlates with nodal status, VEGF-C expression, and prognosis in breast cancer. Breast Cancer Res Treat 91(2):125–132

    Article  PubMed  CAS  Google Scholar 

  2. Kuroi K, Tanaka C, Toi M (2001) Circulating levels of endostatin in cancer patients. Oncol Rep 8(2):405–409

    PubMed  CAS  Google Scholar 

  3. Teh SH, Hill AD, Lee AW, Foley D, Kennedy S, Young L, McDermott E, O’Higgins N (2004) Raised plasma endostatin levels correlate inversely with breast cancer angiogenesis. J Surg Res 116(1):165–171

    Article  PubMed  CAS  Google Scholar 

  4. Zhao J, Yan F, Ju H, Tang J, Qin J (2004) Correlation between serum vascular endothelial growth factor and endostatin levels in patients with breast cancer. Cancer Lett 204:87–95

    Article  PubMed  CAS  Google Scholar 

  5. O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277–285

    Article  PubMed  CAS  Google Scholar 

  6. Hampl M, Tanaka T, Albert PS, Lee J, Ferrari N, Fine HA (2001) Therapeutic effects of viral vector-mediated antiangiogenic gene transfer in malignant ascites. Heman Gene Ther 12(14):1713–1729

    Article  CAS  Google Scholar 

  7. Indraccolo S, Gola E, Rosato A, Minuzzo S, Habeler W, Tisato V, Roni V, Esposito G, Morini M, Albini A, Noonan DM, Ferrantini M, Amadori A, Chieco-Bianchi L (2002) Differential effects of angiostatin, endostatin and interferon-alpha(1) gene transfer on in vivo growth of human breast cancer cells. Gene Ther 9(13):867–878

    Article  PubMed  CAS  Google Scholar 

  8. Cho HM, Rosenblatt JD, Kang YS, Iruela-Arispe ML, Morrison SL, Penichet ML, Kwon YG, Kim TW, Webster KA, Nechustan H, Shin SU (2005) Enhanced inhibition of murine tumor and human breast tumor xenografts using targeted delivery of an antibody-endostatin fusion protein. Mol Cancer Ther 4(6):956–967

    Article  PubMed  CAS  Google Scholar 

  9. Hasle H, Clemmensen IH, Mikkelsen M (2000) Risks of leukaemia and solid tumours in individuals with Down’s syndrome. Lancet 355:165–169

    Article  PubMed  CAS  Google Scholar 

  10. Iughetti P, Suzuki O, Godoi PH, Alves VAF, Sertié AL, Zorick T, Soares F, Camargo A, Moreira ES, Di Loreto C, Moreira-Filho CA, Simpson A, Oliva G, Passos-Bueno MR (2001) A polymorphism in endostatin, an angiogenesis inhibitor, predisposes for the development of prostatic adenocarcinoma. Cancer Res 61:7375–7378

    PubMed  CAS  Google Scholar 

  11. Macpherson GR, Singh AS, Bennett CL, Venzon DJ, DJ, Franks ME, Dahut WL, Kantoff PW, Price DK, Figg WD (2004) Genotyping and functional analysis of the D104N variant of human endostatin. Cancer Biol Ther 3(12):1298–1303

    Article  PubMed  CAS  Google Scholar 

  12. Dixelius J, Cross M, Matsumoto T, Sasaki T, Timpl R, Claesson-Welsh I (2002) Endostatin regulates endothelial cell adhesion and ctytoskeletal organization. Cancer Res 62:1944–1947

    PubMed  CAS  Google Scholar 

  13. Sudhakat A, Sugimoto H, Yang C, Lively J, Zeisberg M, Kalluri R (2003) Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1integrins. Proc Natl Acad Sci USA 100:4766–4771

    Article  CAS  Google Scholar 

  14. Blackhall FH, Merry CL, Lyon M, Jayson GC, Folkman J, Javaherian K, Gallagher JT (2003) Binding of endostatin to endothelial heparan sulphate shows a differential requirement for specific sulphates. Biochem J 375:131–139

    Article  PubMed  CAS  Google Scholar 

  15. MacDonald NJ, Shivers WY, Narum DL, Plum SM, Wingard JN, Fuhrmann SR, Liang H, Holland-Lin J, Chen DH, Sim BK (2001) Endostatin binds tropomyosin: a potential modulator of the antitumor activity of endostatin. J Biol Chem 276:25190–25196

    Article  PubMed  CAS  Google Scholar 

  16. Chang Z, Choon A, Friedl A (1999) Endostatin binds to blood vessels in situ independent of heparan sulphate and does not compete for fibroblast growth factor-2 binding. Am J Pathol 155:71–76

    PubMed  CAS  Google Scholar 

  17. Kim YM, Hwang S, Pyun BJ, Kim TY, Lee ST, Gho YS, Kwon YG (2002) Endostatin blocks vascular endothelial growth factor-mediated signalling via direct interaction with KDR/Flk-1. J Biol Chem 277:27872–27879

    Article  PubMed  CAS  Google Scholar 

  18. Abdollahi A, Hahnfeldt P, Maercker C, Grone HJ, Debus J, Ansorge W, Folkman J, Hlatky L, Huber PE (2004) Endostatin’s antiangiogenic signalling network. Moll Cell 13:649–663

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are indebted to Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support, and to Mr. Roberto Zulli for the statistical analysis.

Author information

Authors and Affiliations

  1. Department of Internal Medicine State, University of Campinas Rua Alexander, Flemming no 181, Cidade Universitária “Zeferino Vaz”, Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-970, Brazil

    Gustavo J. Lourenço, Neiva S. L. Gonçales, Helvia Nascimento, Fernando F. Costa & Carmen S. P. Lima

  2. Department of Obstetric and Gynecology, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil

    Cassio Cardoso-Filho, Julia Y. Shinzato, Luis C. Zeferino & Maria S. C. Gurgel

Authors
  1. Gustavo J. Lourenço
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cassio Cardoso-Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neiva S. L. Gonçales
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Julia Y. Shinzato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luis C. Zeferino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Helvia Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fernando F. Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maria S. C. Gurgel
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carmen S. P. Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carmen S. P. Lima.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lourenço, G., Cardoso-Filho, C., Gonçales, N.L. et al. A high risk of occurrence of sporadic breast cancer in individuals with the 104NN polymorphism of the COL18A1 gene. Breast Cancer Res Treat 100, 335–338 (2006). https://doi.org/10.1007/s10549-006-9259-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-006-9259-z

Keywords

Search

Navigation