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The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer
Department of Oncology, Vejle Hospital, Vejle, Denmark
Department of Biochemistry, Vejle Hospital, Vejle, Denmark
Department of Clinical Pathology, Vejle Hospital, Vejle, Denmark
Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark
* Author to whom correspondence should be addressed.
Received: 24 May 2010; in revised form: 23 June 2010 / Accepted: 25 June 2010 / Published: 28 June 2010
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.
Keywords: colorectal neoplasm; single nucleotide polymorphisms; haplotypes; vascular endothelial growth factor A; survival
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Hansen, T.F.; Spindler, K.-L.; Andersen, R.F.; Lindebjerg, J.; Kølvraa, S.; Brandslund, I.; Jakobsen, A. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer. Cancers 2010, 2, 1405-1418.
Hansen TF, Spindler K-L, Andersen RF, Lindebjerg J, Kølvraa S, Brandslund I, Jakobsen A. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer. Cancers. 2010; 2(3):1405-1418.
Hansen, Torben F.; Spindler, Karen-Lise G.; Andersen, Rikke F.; Lindebjerg, Jan; Kølvraa, Steen; Brandslund, Ivan; Jakobsen, Anders. 2010. "The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer." Cancers 2, no. 3: 1405-1418.