Investigating the association of vascular endothelial growth factor polymorphisms with breast cancer: a Moroccan case–control study

Abstract

The main mediator of breast cancer (BC) angiogenesis is the vascular endothelial growth factor (VEGF). Variation of VEGF-A gene may influence the BC susceptibility. The present case-control study investigated the association of the four commonly studied single nucleotide polymorphisms (SNP) of VEGF-A, namely: -1154A/G (rs1570360), -2578C/A (rs699947), -634G/C (rs2010963) and -460T/C (rs833061) with BC susceptibility and aggressiveness in Moroccan women. After genomic DNA extraction, genotyping was performed by TaqMan SNP assays on 70 BC patients and 70 healthy women. The χ2 test was used to detect differences in the genotype frequencies of VEGF between the groups and to stratify genotypes by the clinico-pathological characteristics in patient's group. Women carriers of -1154AG + AA and -2578AC + AA VEGF genotypes had a reduced risk to develop BC [p = 0.018, OR 2.25 95 % CI (1.14-4.42) and p = 0.022, OR 2.26 95 % CI (1.12-4.58), respectively]. Carriers of -460CT and CT + CC genotypes had also a reduced risk to develop BC [p = 0.045, OR 2.63 95 % CI (1.19-5.84) and p = 0.043, OR 2.12 95 % CI (1.01-4.43), respectively]. Moreover, the A-1154A-2578G-634C-460 haplotype seems to have a protective effect against BC risk [p = 0.007, OR 2.41 95 % CI (1.27-4.55)]. Stratification for BC patients according to clinico-pathological characteristics reveals no association with any of VEGF-A SNPs. In conclusion, the data indicated significant associations of VEGF -1154A/G, -2578C/A and -460T/C polymorphisms with BC susceptibility in Moroccan individuals. These VEGF-A polymorphisms can be useful as predisposing genetic markers for BC. Further larger-scale studies are necessary to confirm our finding.

Prognostic evaluation of VEGFA genotypes and haplotypes in a cohort of Brazilian women with non metastatic breast cancer

“…Our finding of a positive association between variant rs699947 genotypes and high-grade tumors is in opposite direction of that reported by Jin et al, 23 who found an association between variant homozygous AA and low-grade tumors, whereas other authors reported no association between rs699947 and tumor grade. 37,45,46 Likewise, the results indicating positive association of variant genotypes of rs833061 with high histological grade and lymph node metastases at diagnosis also appear to contradict those of Sa-Nguanraksa et al, 44 who reported lower lymphovascular invasion of breast tumors with the variant homozygous genotype CC. The impact of rs833061 in breast cancer has also been studied by Rahoui et al, 37 who found no significant associations with histopathological features.…”

“…37,45,46 Likewise, the results indicating positive association of variant genotypes of rs833061 with high histological grade and lymph node metastases at diagnosis also appear to contradict those of Sa-Nguanraksa et al, 44 who reported lower lymphovascular invasion of breast tumors with the variant homozygous genotype CC. The impact of rs833061 in breast cancer has also been studied by Rahoui et al, 37 who found no significant associations with histopathological features. Nevertheless, the authors only included 70 patients, which limit the statistical power for association analyses.…”

“…22,21,12 VEGFA SNPs were shown to affect VEGFA levels in different cell models, 21,[23][24][25] including breast cancer. 26 VEGFA SNPs have also been associated with breast cancer susceptibility, 11,13,23,[26][27][28][29][30][31][32][33][34][35][36][37][38][39] increased risk of progression 13,[40][41][42][43][44] or poor survival. 13,43 However, most of these works focused on the effects of SNPs evaluated separately, and the results from different authors present great disparity.…”

Vascular endothelial growth factor +405G/C and -2578C/A polymorphisms and breast cancer risk: a meta-analysis

“…Through screening the titles and reading the abstracts and the entire articles, 9 eligible articles were selected for this meta-analysis (Jin et al, 2005;Jacobs et al, 2006;Kataoka et al, 2006;Balasubramanian et al, 2007;Pharoah et al, 2007;Oliveira et al, 2011;Sa-Nguanraksa et al, 2013;James et al, 2014;Rahoui et al, 2014). The flow chart for study selection is summarized in Figure 1.…”

“…For the +405G/C polymorphism, 9 studies were available, including a total of 6054 patients and 6170 controls. There were 4 studies with cohorts of Caucasian descent (Jin et al, 2005;Jacobs et al, 2006;Balasubramanian et al, 2007;Pharoah et al, 2007), 3 studies of Asian descent (Kataoka et al, 2006;Sa-Nguanraksa et al, 2013;James et al, 2014), 1 study of African descent (Rahoui et al, 2014), and 1 study of mixed descent (Oliveira et al, 2011). The HWE test was performed on the genotype distributions of the controls, and all studies were in agreement with HWE except Oliveira et al (2011) and Sa-Nguanraksa et al (2013).…”