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

Abstract

ABSTRACTVascular Endothelial Growth Factor (VEGF) mediates angiogenesis, which is crucial for tumor development and progression. The present study aimed to evaluate the impact of VEGFA gene polymorphisms rs699947, rs833061, rs1570360, rs2010963 and rs3025039 on breast cancer features and prognosis. A cohort of Brazilian women (N = 1038) with unilateral non-metastatic breast cancer was evaluated. The association between VEGFA polymorphisms and histopathological features or pathological complete response (pCR) to neoadjuvant chemotherapy was evaluated by the Chi-square test, with calculation of the respective odds ratio (OR) and 95% confidence intervals (95% CI). The impact of individual categories on disease-free survival was evaluated using Kaplan-Meier curves and multivariate Cox proportional hazards regression models for calculation of adjusted hazard ratios (HRadjusted). Variant genotypes of rs699947 (CA + AA) were significantly associated with high-grade (G2 + G3) tumors (OR = 1.82; 95% CI = 1.15 – 2.89), and with shorter disease-free survival among patients treated with neoadjuvant chemotherapy followed by mastectomy (HRadjusted = 1.82; 95% CI = 1.16 – 2.86). Variant genotypes of rs833061 (TC + CC) were significantly associated with high-grade (G2 + G3) tumors (OR = 1.79; 95% CI = 1.12 – 2.84) and with positive lymph node status (OR = 1.34; 95% CI = 1.01 – 1.77), but showed no independent effect on disease-free survival. Variant haplotypes (*2 to *5) appear to favor pCR (OR = 7.1; 95% CI = 1.7 – 30.1). VEGFA genotyping may add to prognostic evaluation of breast cancer, with rs699947 being the most likely to contribute.