174 The prognostic value of angiogenesis genes polymorphisms in women with infiltrating ductal breast carcinoma

Abstract

Background: Angiogenesis is an important step in the development of infiltrating ductal carcinoma which is the most common histologic type of breast cancer. Polymorphisms in genes encoding angiogenic factors or their receptors are known to predispose to breast cancer [Schneider et al., 2008; Clar et al., 2009]. The aim of our study was to investigate the association of functional polymorphisms in the VEGF-2578C/A (rs699947), FGFR2A/G (rs1219648), TGFB1-509C>T (rs1800469) and IL10-592C>A (rs1800872) genes with infiltrating ductal breast carcinoma risk, progression and response to neoadjuvant chemotherapy. Material and Methods: Two hundred sixteen patients with operable primary infiltrating ductal breast carcinoma (T1-4N0-2M0; age from 20 to 77 years) who received two-four cycles of neoadjuvant chemotherapy in the Tomsk Cancer Research Institute were included in the present study. The healthy women (n = 286; age from 30 to 75 years) from Western Siberian region were used as the control group. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism protocols. Results: The frequencies of VEGF-2578A/A, FGFR2G/G and IL10-592A/A variants were significantly higher in the patient group when compared with controls (OR= 2.3, p = 0.002; OR= 2.3, p = 0.002 and OR= 3.2, p= 0.008 respectively). Significantly lower frequencies of FGFR2A/A and TGFB1-509TT genotypes were showed in the patient group in comparison to the controls (p= 0.008 and p = 0.03 respectively). We have observed an increased frequency in the VEGF-2578A/A genotype among women with positive regional lymph node metastases compared to patients with negative regional lymph node metastases (p= 0.02). A significant difference was found between the luminal B and luminal A subtype tumor of patients carrying the VEGF-2578C/C genotype (p =0.04). In addition, patients with the FGFR2A/A genotype exhibited a non-statistically significant better response to neoadjuvant chemotherapy (p= 0.06). There was also trend for association between FGFR2G/G genotype and worse response to neoadju-vant chemotherapy in infiltrating ductal breast carcinoma patients (p = 0.08). Conclusions: These findings indicate that genetic variants in VEGF-2578A/A, FGFR2G/G and IL10-592A/A are associated with infiltrating ductal breast carcinoma risk. Polymorphism in VEGF gene may serve as molecular marker related with regional metastasis and molecular subtype of tumor. The polymorphic variants of FGFR2 gene may be a potential prognostic factor for response to neoadjuvant chemotherapy in infiltrating ductal breast carcinoma patients.