Vascular Endothelial Growth Factor A c.*237C>T polymorphism is associated with bevacizumab efficacy and related hypertension in metastatic colorectal cancer

Background No predictive marker has been yet identified for bevacizumab which is widely used in metastatic colorectal cancer. Aims Evaluate impact of single nucleotide polymorphisms involved in Vascular Endothelial Growth Factor pathway on efficacy and tolerance of bevacizumab. Methods We retrospectively included patients who were treated with bevacizumab-based chemotherapy for metastatic colorectal cancer, and for whom a deoxyribonucleic acid sample was available. Ten polymorphisms in Vascular Endothelial Growth Factor-A, his receptors and hypoxia inducible factor-1α were genotyped on germ line DNA using real-time polymerase chain reaction TaqMan®. Results 89 patients were included. The CC genotype for rs3025039 (Vascular Endothelial Growth Factor-A c.*237C>T) was associated with a significantly better time to treatment failure (14.2 months) as compared to the CT and TT genotypes (6.0 months) in univariate (p = 0.004) and multivariate (p = 0.022; HR = 0.57; 95% CI [0.35–0.92]) analysis. Patients with at least one T allele showed worse overall survival and progression-free survival as compared to homozygous CC patients in univariate analysis (respectively p = 0.016 and p = 0.044). There was significantly more severe hypertension for the CC genotype (29.5%) compared to CT and TT genotypes (7.1%) (p = 0.022) in multivariate analysis. Conclusions In this retrospective study, the rs3025039 polymorphism was significantly associated with time to treatment failure and hypertension in patients treated with bevacizumab-based chemotherapy.