Kim Jong Gwang, Chae Yee Soo, Sohn Sang Kyun, Cho Yoon Young, Moon Joon Ho, Park Jae Yong, Jeon Seoung Woo, Lee In Taek, Choi Gyu Seog, Jun Soo-Han
Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea.
Clin Cancer Res. 2008 Jan 1;14(1):62-6. doi: 10.1158/1078-0432.CCR-07-1537.
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.
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.
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).
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.
血管内皮生长因子（VEGF）或其家族可能在淋巴管生成和淋巴肿瘤扩散中起重要作用，从而影响结直肠癌的预后。因此，本研究分析了VEGF基因多态性及其对结直肠癌患者预后的影响。
本研究纳入了445例接受手术治疗的结直肠腺癌患者。从新鲜的结直肠组织中提取基因组DNA，并使用PCR/变性高效液相色谱法测定三种VEGF（-2578C>A、-634G>C和+936C>T）基因多态性。
多因素生存分析显示，-634 G/C基因型（总生存[OS]：风险比[HR]，0.158；P<0.001）或C/C基因型（OS：HR，0.188；P<0.001）患者的生存率优于-634G/G基因型患者，而+936 C/T基因型（OS：HR，12.809；P<0.001）或T/T基因型（OS：HR，37.260；P<0.001）与+936 C/C基因型相比，生存率较差。在单倍型分析中，与野生型-2578C/-634G/+936C单倍型相比，-2578A/-634G/+936T单倍型的生存率显著较差（OS：HR，3.866；P<0.001）。
发现VEGF基因多态性是结直肠癌患者的独立预后标志物。因此，分析VEGF基因多态性有助于识别疾病预后不良高风险的患者亚组。
