Breast Cancer Research and Treatment

, Volume 109, Issue 2, pp 297–304 | Cite as

Genetic polymorphisms in the vascular endothelial growth factor gene and breast cancer risk. The Austrian “tumor of breast tissue: incidence, genetics, and environmental risk factors” study

  • Uwe Langsenlehner
  • Gerald Wolf
  • Tanja Langsenlehner
  • Armin Gerger
  • Günter Hofmann
  • Heimo Clar
  • Thomas C. Wascher
  • Bernhard Paulweber
  • Hellmut Samonigg
  • Peter Krippl
  • Wilfried Renner
Preclinical Study

Abstract

Purpose

Vascular endothelial growth factor (VEGF) is a key regulator of tumor-induced angiogenesis and is required for growth of tumors. We tested the hypothesis that VEGF gene polymorphisms may be associated with breast cancer.

Experimental design

We performed a case–control study including 804 female incident breast cancer patients and 804 female age-matched healthy control subjects. We selected seven VEGF candidate polymorphisms and determined genotypes by 5′-nuclease (TaqMan) assays. Furthermore, VEGF plasma levels and genotypes were analyzed in a group of 81 healthy volunteers (64 men and 17 women).

Results

Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms upstream of the coding sequence (promoter and 5′ untranslated region) and two polymorphisms downstream of the coding sequence. None of the single polymorphisms or haplotypes was significantly associated with the presence of breast cancer. After Bonferroni correction for multiple testing, only one statistical signifcant association between VEGF genotypes and haplotypes and tumor characteristics was observed (-634C allele and small tumor size; p < 0.001). In a multivariate regression analysis including sex, age, VEGF genotypes, and haplotypes as covariates and VEGF plasma level as dependent variable, none of the VEGF polymorphism or haplotypes was a significant predictor of VEGF plasma levels.

Conclusions

Our findings do not support the hypothesis that VEGF polymorphisms are associated with breast cancer risk. The association of the VEGF -634C allele with small tumor size is in clear contrast to a previous publication and should be interpreted with caution until replicated by additional studies.

Keywords

Breast cancer Vegf polymorphisms Haplotypes Genetics Epidemiology Vegf plasma levels 

Notes

Acknowledgment

This study was supported by the Anniversary Fund of the Österreichische Nationalbank (Project Nr. 10609).

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Uwe Langsenlehner
    • 1
  • Gerald Wolf
    • 2
  • Tanja Langsenlehner
    • 3
  • Armin Gerger
    • 1
  • Günter Hofmann
    • 1
  • Heimo Clar
    • 4
  • Thomas C. Wascher
    • 5
  • Bernhard Paulweber
    • 6
  • Hellmut Samonigg
    • 1
  • Peter Krippl
    • 7
  • Wilfried Renner
    • 8
  1. 1.Department of Internal Medicine, Division of OncologyMedical University GrazGrazAustria
  2. 2.Department of Radiology and Nuclear MedicineGeneral Hospital LeobenLeobenAustria
  3. 3.Department of Therapeutic Radiology and OncologyMedical University GrazGrazAustria
  4. 4.Department of Orthopaedic SurgeryMedical University GrazGrazAustria
  5. 5.Department of Internal MedicineMedical University GrazGrazAustria
  6. 6.Department of Internal MedicineMedical University SalzburgSalzburgAustria
  7. 7.Department of Internal MedicineGeneral Hospital FürstenfeldFurstenfeldAustria
  8. 8.Clinical Institute of Medical and Laboratory DiagnosticsMedical University GrazGrazAustria

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