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Vascular Endothelial Growth Factor Gene Polymorphisms Associated with Prognosis for Patients with Colorectal Cancer

Authors' Affiliations: Departments of ¹ Oncology/Hematology, ² Internal Medicine and Biochemistry, ³ Internal Medicine, and ⁴ Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea

Requests for reprints: Gyu Seog Choi, Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 50 Samduck 2-Ga, Jung-Gu, Daegu 700-712, Korea. Phone: 82-53-420-6522; Fax: 82-53-426-2046; E-mail: kyuschoi{at}mail.knu.ac.kr and Jong Gwang Kim, Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 50 Samduck 2-Ga, Jung-Gu, Daegu 700-712, Korea. Phone: 82-53-420-6522; Fax: 82-53-426-2046; E-mail: jkk21c{at}mail.knu.ac.kr.

Purpose: Vascular endothelial growth factor (VEGF) or its family may be considered to play an important role in lymphangiogenesis and lymphatic tumor spread, thereby affecting prognosis of colorectal cancer. Accordingly, the present study analyzed VEGF gene polymorphisms and their effect on the prognosis for patients with colorectal cancer.

Experimental Design: Four hundred and forty-five consecutive patients with surgically treated colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and three VEGF (–2578C>A, –634G>C, and +936C>T) gene polymorphisms were determined using a PCR/denaturing high-performance liquid chromatography assay.

Results: Multivariate survival analysis showed that the survival for the patients with the –634 G/C genotype [overall survival (OS): hazard ratio (HR), 0.158; P < 0.001] or C/C genotype (OS: HR, 0.188; P < 0.001) were better than for the patients with the –634G/G genotype, whereas the +936 C/T genotype (OS: HR, 12.809; P < 0.001) or T/T genotype (OS: HR, 37.260; P < 0.001) was associated with a worse survival compared with the +936 C/C genotype. In haplotype analysis, the –2578A/–634G/+936T haplotype exhibited a significantly worse survival when compared with the wild –2578C/–634G/+936C haplotype (OS: HR, 3.866; P < 0.001).

Conclusions: VEGF gene polymorphisms were found to be an independent prognostic marker for patients with colorectal cancer. Accordingly, the analysis of VEGF gene polymorphisms can help identify patient subgroups at high risk of a poor disease outcome.