RT Journal Article
SR Electronic
T1 Vascular Endothelial Growth Factor Polymorphisms in Relation to Breast Cancer Development and Prognosis
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 3647
OP 3653
DO 10.1158/1078-0432.CCR-04-1803
VO 11
IS 10
A1 Jin, Qianren
A1 Hemminki, Kari
A1 Enquist, Kerstin
A1 Lenner, Per
A1 Grzybowska, Ewa
A1 Klaes, Rüdiger
A1 Henriksson, Roger
A1 Chen, Bowang
A1 Pamula, Jolanta
A1 Pekala, Wioletta
A1 Zientek, Helena
A1 Rogozinska-Szczepka, Jadwiga
A1 Utracka-Hutka, Beata
A1 Hallmans, Göran
A1 Försti, Asta
YR 2005
UL http://clincancerres.aacrjournals.org/content/11/10/3647.abstract
AB Purpose: 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. Experimental Design: 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.