title: The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer: results from the Nordic ACT trial.
abstract: OBJECTIVE
  Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) system in this setting.
  
  
  METHODS
  Pre-treatment blood samples and response evaluations were available from 218 of the 249 included patients. All patients received bevacizumab and chemotherapy comprising fluorouracil and leucovorin or capecitabine combined with either oxaliplatin (FOLFOX or XELOX, n = 183) or irinotecan (FOLFIRI or XELIRI, n = 66). Germline DNA was isolated from whole blood, and five SNPs in the VEGF-A gene, one SNP in the VEGF receptor 1 (VEGFR-1) gene and three SNPs in the VEGFR-2 gene were analysed by polymerase chain reaction. Response was evaluated according to RECIST version 1.0, and the association to genotypes was analysed using Fisher's exact test.
  
  
  RESULTS
  The VEGFR-1 319 C/A SNP was significantly associated with response. Objective response was observed in 36% of the patients with CC genotype, 40% with CA and 56% with AA, p = 0.048. The response rates also differed significantly between patients with C-allele containing genotypes (CC + CA) (39%) and patients homozygous for the A-allele (AA) (56%), p = 0.015. There was no correlation between response rates and the remaining SNPs.
  
  
  CONCLUSIONS
  The VEGFR-1 319 C/A SNP is a potential predictive marker for bevacizumab plus chemotherapy in patients with mCRC. Patients with the A allele appeared to have increased response rates. The results call for validation.
authors.affiliation: Danish Colorectal Cancer Group South, Vejle Hospital, University of Southern Denmark, Vejle, Denmark. torben.hansen@slb.regionsyddanmark.dk
authors.forename: Torben Frøstrup
authors.initials: TF
authors.lastname: Hansen
authors.forename: René dePont
authors.initials: Rd
authors.lastname: Christensen
authors.forename: Rikke Fredslund
authors.initials: RF
authors.lastname: Andersen
authors.forename: Karen-Lise
authors.initials: KL
authors.lastname: Garm Spindler
authors.forename: Anders
authors.initials: A
authors.lastname: Johnsson
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D003718:Denmark; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D013548:Sweden; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab