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.
OBJECTIVE
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.


METHODS
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.
Langsenlehner
Uwe
U
Department of Internal Medicine, Division of Oncology, Medical University Graz, Graz, Austria. uwe.langsenlehner@klinikum-graz.at
Wolf
Gerald
G
Langsenlehner
Tanja
T
Gerger
Armin
A
Hofmann
Günter
G
Clar
Heimo
H
Wascher
Thomas C
TC
Paulweber
Bernhard
B
Samonigg
Hellmut
H
Krippl
Peter
P
Renner
Wilfried
W
D001317:Austria / Q000453:epidemiology; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004781:Environmental Exposure; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A