Vascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis.
OBJECTIVE
Angiogenesis is a necessary step in tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is a major mediator of breast cancer angiogenesis. Therefore, we investigated the association of polymorphisms in the VEGF gene with breast cancer risk and prognostic characteristics of the tumors in a large case-control study.


METHODS
We examined three polymorphisms in the VEGF gene (-2578C/A, -1154G/A, and +936C/T) in 571 familial breast cancer cases from Poland and Germany and -2578C/A, -634G/C, and +936C/T polymorphisms in 974 unselected breast cancer cases from Sweden together with ethnically and geographically selected controls.


RESULTS
None of the polymorphisms or any haplotype was significantly associated with either familial or unselected breast cancers. Our study suggests that the +936C/T polymorphism is unlikely to be associated with breast cancer. We also analyzed the unselected cases for genotypes or haplotypes that associated with tumor characteristics. The -634CC genotype and the -2578/-634 CC haplotype were significantly associated with high tumor aggressiveness (large tumor size and high histologic grade, P < 0.01) and the -2578AA genotype and the -2578/-634 AG haplotype with low histologic grade tumors (P = 0.04). The genotypes and haplotypes were not related with other tumor characteristics such as regional or distant metastasis, stage at diagnosis, or estrogen or progesterone receptor status.


CONCLUSIONS
Although none of the polymorphisms studied in the VEGF gene was found to influence susceptibility to breast cancer significantly, some of the VEGF genotypes and haplotypes may influence tumor growth through an altered expression of VEGF and tumor angiogenesis.
Jin
Qianren
Q
Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden. qianren.jin@cnt.ki.se
Hemminki
Kari
K
Enquist
Kerstin
K
Lenner
Per
P
Grzybowska
Ewa
E
Klaes
Rüdiger
R
Henriksson
Roger
R
Chen
Bowang
B
Pamula
Jolanta
J
Pekala
Wioletta
W
Zientek
Helena
H
Rogozinska-Szczepka
Jadwiga
J
Utracka-Hutka
Beata
B
Hallmans
Göran
G
Försti
Asta
A
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D010375:Pedigree; D011110:Polymorphism, Genetic; D011379:Prognosis; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A