title: The prognostic value of haplotypes in the vascular endothelial growth factor a gene in colorectal cancer.
abstract: New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study was to investigate the prognostic importance of haplotypes in the VEGF-A gene in patients with CRC. The study included 486 patients surgically resected for stage II and III CRC, divided into two independent cohorts. Three SNPs in the VEGF-A gene were analyzed by polymerase chain reaction. Haplotypes were estimated using the PHASE program. The prognostic influence was evaluated using Kaplan-Meir plots and log rank tests. Cox regression method was used to analyze the independent prognostic importance of different markers. All three SNPs were significantly related to survival. A haplotype combination, responsible for this effect, was present in approximately 30% of the patients and demonstrated a significant relationship with poor survival, and it remained an independent prognostic marker after multivariate analysis, hazard ratio 2.46 (95% confidence interval 1.49-4.06), p < 0.001. Validation was provided by consistent findings in a second and independent cohort. Haplotype combinations call for further investigation.
authors.affiliation: Department of Oncology, Vejle Hospital, Vejle, Denmark. torben.hansen@slb.regionsyddanmark.dk.
authors.forename: Torben F
authors.initials: TF
authors.lastname: Hansen
authors.forename: Karen-Lise G
authors.initials: KL
authors.lastname: Spindler
authors.forename: Rikke F
authors.initials: RF
authors.lastname: Andersen
authors.forename: Jan
authors.initials: J
authors.lastname: Lindebjerg
authors.forename: Steen
authors.initials: S
authors.lastname: Kølvraa
authors.forename: Ivan
authors.initials: I
authors.lastname: Brandslund
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen