Kong Sun-Young, Park Joong-Won, Lee Jung An, Park Jung Eun, Park Kyung Woo, Hong Eun Kyung, Kim Chang-Min
Center for Clinical Services, Department of Laboratory Medicine, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
Hepatology. 2007 Aug;46(2):446-55. doi: 10.1002/hep.21720.
Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and progression of tumor, including hepatocellular carcinoma (HCC), and elevated VEGF levels in serum and tissues have been known to be related with poor prognosis in patients with HCC. However, the effect of such polymorphisms of the VEGF gene on HCC prognosis has not been elucidated. In the present study, we investigated the association between VEGF gene polymorphisms and HCC patient prognosis. The study involved 416 HCC patients treated at the National Cancer Center Korea from November 2000 to December 2005. The median patient age was 57 years, and 328 patients (78.8%) were men. A total of 19 polymorphisms were analyzed, and the hazard ratios (HRs) for genotypes and haplotypes were determined in terms of risk for overall survival using Cox proportional hazard regression analysis. Of the 19 alleles, 7 showed no heterozygous allele. PHASE analysis identified a total of 36 haplotypes. The -2578 to -1498 region of the VEGF gene showed a strong linkage disequilibrium (correlation coefficient, r(2) = 0.91; Lewontin's D', D' = 0.982). The adjusted HRs were 0.67 [95% confidence interval (CI), 0.46 to 0.99] for -634CC genotype carriers and 0.57 (95% CI, 0.36 to 0.92) for homozygous haplotype 1 (Ht1: CCGAGCCC at -2578/-1203/-1190/-1179/-1154/-634/-7/+936) carriers compared with noncarriers.
These findings suggest that VEGF polymorphisms may be significant prognostic indicators for HCC patients.
血管内皮生长因子（VEGF）在包括肝细胞癌（HCC）在内的肿瘤血管生成和进展中起重要作用，血清和组织中VEGF水平升高已知与HCC患者的不良预后相关。然而，VEGF基因的此类多态性对HCC预后的影响尚未阐明。在本研究中，我们调查了VEGF基因多态性与HCC患者预后之间的关联。该研究纳入了2000年11月至2005年12月在韩国国立癌症中心接受治疗的416例HCC患者。患者中位年龄为57岁，328例患者（78.8%）为男性。共分析了19个多态性位点，并使用Cox比例风险回归分析确定了基因型和单倍型的风险比（HRs），以评估总生存风险。在这19个等位基因中，7个未显示杂合等位基因。PHASE分析共鉴定出36种单倍型。VEGF基因的-2578至-1498区域显示出强连锁不平衡（相关系数，r(2)=0.91；Lewontin's D'，D'=0.982）。与非携带者相比，-634CC基因型携带者的校正HR为0.67[95%置信区间（CI），0.46至0.99]，纯合单倍型1（Ht1：-2578/-1203/-1190/-1179/-1154/-634/-7/+936处的CCGAGCCC）携带者的校正HR为0.57（95%CI，0.36至0.92）。
这些发现表明VEGF多态性可能是HCC患者重要的预后指标。
