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01-05-2008 | Preclinical Study

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

Authors: Uwe Langsenlehner, Gerald Wolf, Tanja Langsenlehner, Armin Gerger, Günter Hofmann, Heimo Clar, Thomas C. Wascher, Bernhard Paulweber, Hellmut Samonigg, Peter Krippl, Wilfried Renner

Published in: Breast Cancer Research and Treatment | Issue 2/2008

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.

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Title: 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
Authors: Uwe Langsenlehner
Gerald Wolf
Tanja Langsenlehner
Armin Gerger
Günter Hofmann
Heimo Clar
Thomas C. Wascher
Bernhard Paulweber
Hellmut Samonigg
Peter Krippl
Wilfried Renner
Publication date: 01-05-2008
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2008
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-007-9655-z

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Abstract

Purpose

Experimental design

Results

Conclusions

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