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血管内皮生长因子(VEGF)基因多态性与血清 VEGF 浓度升高与胰腺腺癌的关系。

Association of vascular endothelial growth factor (VEGF) gene polymorphism and increased serum VEGF concentration with pancreatic adenocarcinoma.

机构信息

Department of Basic Sciences, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Somajiguda, Hyderabad, Andhra Pradesh, India.

出版信息

Pancreatology. 2013 May-Jun;13(3):267-72. doi: 10.1016/j.pan.2013.02.006. Epub 2013 Mar 14.

Abstract

UNLABELLED

BACKGROUND &AIM: Pancreatic cancer is related to high mortality rate. The vascular endothelial growth factor (VEGF) has a strong influence in tumor-related angiogenesis having association with the grade of angiogenesis and the prognosis of different solid tumors including pancreatic cancer. The present study was aimed to analyze the genotype and haplotype distribution of VEGF gene single nucleotide polymorphisms (SNPs), -460T/C, +405G/C, +936C/T, in patients with pancreatic adenocarcinoma from South India, and the effect of these SNPs on serum VEGF level.

METHODS

Total 80 patients with pancreatic adenocarcinoma and 87 controls were recruited. The genotype of VEGF gene polymorphisms was determined in both patients and controls using polymerase chain reaction-restriction fragment length polymorphism method. The serum VEGF protein was estimated by standard enzyme-linked immunosorbent assay.

RESULTS

The genotype, +405G/G of VEGF gene showed a significant association with the patients with pancreatic adenocarcinoma (P = 0.012, Odds ratio: 2.133), whereas no significant difference was found in the genotype distribution of SNPs, -460C/T and +936C/T between patient and control groups (P > 0.05). Serum VEGF level was found to be significantly high in patients (1315.10 pg/Ml, SD ± 230.79) when compared to controls (591.35 pg/mL, SD ± 92.48) (P < 0.0001), which showed a strong genotype-phenotype correlation between genotype +405G/G and serum VEGF level. Further, the haplotype C-G-T showed a strong association with the disease, and no specific haplotype was associated with increased serum VEGF level.

CONCLUSION

The polymorphism, +405G/C but not -460T/C and +936C/T, of VEGF gene is strongly associated with pancreatic adenocarcinoma, and this SNP has significant influence on serum VEGF level.

摘要

目的

胰腺癌死亡率较高,血管内皮生长因子(VEGF)在肿瘤相关血管生成中具有重要作用,与不同实体肿瘤(包括胰腺癌)的血管生成程度和预后有关。本研究旨在分析印度南部胰腺癌患者血管内皮生长因子基因单核苷酸多态性(SNP)-460T/C、+405G/C、+936C/T 的基因型和单倍型分布,以及这些 SNP 对血清 VEGF 水平的影响。

方法

共纳入 80 例胰腺癌患者和 87 例对照。采用聚合酶链反应-限制性片段长度多态性方法检测 VEGF 基因多态性在患者和对照中的基因型。采用标准酶联免疫吸附试验测定血清 VEGF 蛋白。

结果

VEGF 基因的基因型+405G/G 与胰腺癌患者显著相关(P=0.012,优势比:2.133),而-460C/T 和+936C/T 三个 SNP 的基因型分布在患者和对照组之间无显著差异(P>0.05)。与对照组相比,患者的血清 VEGF 水平明显升高(1315.10pg/ml,SD±230.79)(P<0.0001),且基因型+405G/G 与血清 VEGF 水平之间存在强烈的基因型-表型相关性。此外,C-G-T 单倍型与疾病有很强的关联性,没有特定的单倍型与血清 VEGF 水平升高有关。

结论

VEGF 基因的多态性+405G/C 而不是-460T/C 和+936C/T 与胰腺癌密切相关,该 SNP 对血清 VEGF 水平有显著影响。

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