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.
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.
Authors: Vincenzo Formica; Raffaele Palmirotta; Girolamo Del Monte; Annalisa Savonarola; Giorgia Ludovici; Maria Laura De Marchis; Italia Grenga; Michele Schirru; Fiorella Guadagni; Mario Roselli Journal: Int J Colorectal Dis Date: 2010-12-29 Impact factor: 2.571
Authors: Bryan P Schneider; Molin Wang; Milan Radovich; George W Sledge; Sunil Badve; Ann Thor; David A Flockhart; Bradley Hancock; Nancy Davidson; Julie Gralow; Maura Dickler; Edith A Perez; Melody Cobleigh; Tamara Shenkier; Susan Edgerton; Kathy D Miller Journal: J Clin Oncol Date: 2008-10-01 Impact factor: 44.544