title: 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.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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).
  
  
  RESULTS
  The vascular endothelial growth factor A (VEGFA) 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 (FLT1) 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 FLT1 rs9513070/rs9554320/rs9582036 GCA haplotype was associated with inferior PFS and OS (p = 0.004 and p = 0.041, respectively).
  
  
  CONCLUSIONS
  The VEGFA rs833061 SNP is associated with the ORR, and the FLT1 rs9513070 SNP and FLT1 GCA haplotypes are associated with PFS and OS in advanced CRC patients treated with cytotoxic chemotherapy plus bevacizumab.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Byeong Seok
authors.initials: BS
authors.lastname: Sohn
authors.forename: Seong Joon
authors.initials: SJ
authors.lastname: Park
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Kyu-Pyo
authors.initials: KP
authors.lastname: Kim
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Hong
authors.forename: Cheolwon
authors.initials: C
authors.lastname: Suh
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1