Supplementary Material for: Single-Nucleotide Polymorphisms in the Vascular Endothelial Growth Factor Pathway and Outcomes of Patients Treated with First-Line Cytotoxic Chemotherapy Combined with Bevacizumab for Advanced Colorectal Cancer
2014-08-15T00:00:00Z (GMT) by
<b><i>Objective:</i></b> The aim of this study was to evaluate the association between the efficacy of first-line cytotoxic chemotherapy plus bevacizumab and single-nucleotide polymorphisms (SNPs) of angiogenic genes in patients with advanced colorectal cancer (CRC). <b><i>Methods:</i></b> DNA was extracted from blood samples of 125 patients, and 12 SNPs were evaluated for association with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). <b><i>Results:</i></b> The vascular endothelial growth factor A <i>(VEGFA)</i> rs833061 T/T was associated with superior ORR compared to its alternative genotypes (75.9 vs. 50.8%; p = 0.008), and the interleukin 8 rs4073 A/A genotype tended to be associated with poor ORR (45.0 vs. 66.0%; p = 0.067). The median PFS and OS were superior in patients with the fms-related tyrosine kinase 1 <i>(FLT1)</i> rs9513070 A/A genotype (8.7 vs. 6.6 months; p = 0.001 and 26.4 vs. 16.1 months; p = 0.038, respectively). The kinase insert domain receptor rs1531289 G/G genotype tended to be associated with improved PFS (8.0 vs. 7.1 months; p = 0.069). In haplotype analysis, the <i>FLT1</i> rs9513070/rs9554320/rs9582036 GCA haplotype was associated with inferior PFS and OS (p = 0.004 and p = 0.041, respectively). <b><i>Conclusion:</i></b> The <i>VEGFA</i> rs833061 SNP is associated with the ORR, and the <i>FLT1</i> rs9513070 SNP and <i>FLT1</i> GCA haplotypes are associated with PFS and OS in advanced CRC patients treated with cytotoxic chemotherapy plus bevacizumab.