Association between vascular endothelial growth factor gene polymorphisms and survival in hepatocellular carcinoma patients
Association between vascular endothelial growth factor gene polymorphisms and survival in hepatocellular carcinoma patients
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DOI：
10.1002/hep.21720
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发表时间：
2007-08-01
期刊：
影响因子：
13.5
通讯作者：
Mm, Chang-Min
中科院分区：
文献类型：
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作者：
Kong, Sun-Young;Park, Joong-Won;Mm, Chang-Min
血管内皮生长因子在包括肝细胞癌在内的肿瘤的血管生成和进展中起重要作用，血清和组织中的血管内皮生长因子水平升高与肝细胞癌患者的预后不良有关。然而，血管内皮生长因子基因的这种多态对肝细胞癌预后的影响尚不清楚。在本研究中，我们探讨了血管内皮生长因子基因多态性与肝癌患者预后的关系。这项研究涉及2000年11月至2005年12月在韩国国家癌症中心接受治疗的416名肝癌患者。患者年龄中位数为57岁，其中328名患者(78.8%)为男性。共分析了19个基因多态性，并用COX比例风险回归分析确定了基因型和单倍型的风险比(HR)。在19个等位基因中，7个没有杂合等位基因。时相分析共鉴定出36种单倍型。血管内皮生长因子基因-2578~-1498区域存在较强的连锁不平衡(相关系数r(2)=0.91；勒文顿氏‘s D’=0.982)。与非携带者相比，-634CC基因携带者和纯合子1(HT1：CCGAGCCC at-2578/-1203/-1190/-1179/-1154/-634/-7/+936)携带者的校正命中率分别为0.67[95%可信区间(CI)0.46~0.99]和0.57(95%CI，0.36~0.92)。结论：血管内皮生长因子基因多态性可能是影响肝癌患者预后的重要指标。
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 Hits 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. Conclusion: These findings suggest that VEGF polymorphisms may be significant prognostic indicators for HCC patients.