The single nucleotide polymorphism +936 C/T VEGF is associated with human epidermal growth factor receptor 2 expression in Moroccan breast cancer women.

The vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is involved in the development and progression of breast cancer (BC). The functional +936 C/T polymorphism of the VEGF-A gene has been implicated in BC susceptibility; however, published data are conflicting. In the current case-control study, we analyzed the association of the +936 C/T polymorphism with BC risk and tumor markers expression, human epidermal growth factor receptor 2 (HER2/neu) and caner antigen 15.3 (CA 15.3) in Moroccan women. We genotyped the DNA of 70 BC patients and 70 healthy women by TaqMan SNP assays. The χ(2) test and Fisher's exact test were used for statistical analyses. The overall results revealed that there is no association between the +936 C/T polymorphism and BC risk [p = 0.8; OR 0.87, 95 % CI (0.32-2.42)]. However, when we stratified the group of patients according to the status of tumor markers, a statistical significant association of +936 C/T SNP and HER2/neu expression was observed (p = 0.009). In contrast, no association with the other tumor marker, CA 15.3, was found (p = 0.090). Thus, the +936 C/T polymorphism seems to have a correlation with HER/neu expression in BC disease.

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

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.

Mutation screening of the BRCA1 gene in early onset and familial breast/ovarian cancer in Moroccan population.

Worldwide variation in the distribution of BRCA mutations is well recognised, and for the Moroccan population no comprehensive studies about BRCA mutation spectra or frequencies have been published. We therefore performed mutation analysis of the BRCA1 gene in 121 Moroccan women diagnosed with breast cancer. All cases completed epidemiology and family history questionnaires and provided a DNA sample for BRCA testing. Mutation analysis was performed by direct DNA sequencing of all coding exons and flanking intron sequences of the BRCA1 gene. 31.6 % (6/19) of familial cases and 1 % (1/102) of early-onset sporadic (< 45 years)were found to be associated with BRCA1 mutations. The pathogenic mutations included two frame-shift mutations (c.798_799delTT, c.1016dupA), one missense mutation (c.5095C>T),and one nonsense mutation (c.4942A>T). The c.798_799delTT mutation was also observed in Algerian and Tunisian BC families, suggesting the first non-Jewish founder mutation to be described in Northern Africa. In addition, ten different unclassified variants were detected in BRCA1, none of which were predicted to affect splicing. Most unclassified variants were placed in Align-GVGD classes suggesting neutrality. c.5117G>C involves a highly conserved amino acid suggestive of interfering with function (Align-GVGD class C55), but has been observed in conjunction with a deleterious mutation in a Tunisian family. These findings reflect the genetic heterogeneity of the Moroccan population and are relevant to genetic counselling and clinical management. The role of BRCA2 in BC is also under study.