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血管内皮生长因子基因多态性与结直肠癌易感性

VEGF gene polymorphisms and susceptibility to colorectal cancer.

作者信息

Jannuzzi Ayşe Tarbın, Özhan Gül, Yanar Hakan Teoman, Alpertunga Buket

机构信息

1 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University , Istanbul, Turkey .

出版信息

Genet Test Mol Biomarkers. 2015 Mar;19(3):133-7. doi: 10.1089/gtmb.2014.0259. Epub 2015 Jan 30.

Abstract

AIMS

Colorectal cancer (CRC) is the third most common cancer in the world and its etiology involves the interaction of genetic and environmental factors. New blood vessels form through a process called angiogenesis and have an essential role in tumor growth, progression, and metastasis of malignant tumors. The vascular endothelial growth factor (VEGF), one of the most important angiogenic factors, is a specific mitogen for vascular endothelial cells. In the present case-control study, we carried out the study to evaluate whether the VEGF single-nucleotide polymorphisms play a role in modulating susceptibility to CRC.

METHODS

We evaluated the VEGF -2578A>C, +936C>T, and -460C>T genotypes obtained from 103 patients with CRC and 129 healthy controls by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Also, haplotype analysis was determined. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated.

RESULTS

-2578A>C was significantly associated with CRC risk (OR 1.81; 95% CI 0.94-3.47; p=0.0495), while distribution of +936C>T and -460C>T genotypes in cases and controls did not significantly differ. The VEGF A2578-T936-T460 haplotype might be associated with the development of CRC (OR 8.77; 95% CI 1.05-73.36; p=0.0434). There was significant haplotype effect for all eight haplotypes (p=0.02).

CONCLUSIONS

These results suggest that the VEGF polymorphisms might play a role in the development of CRC. Therefore, the VEGF polymorphisms might be further investigated to use in the determination of risk factors for CRC and to have a predictive value for anti-VEGF-targeted cancer therapies.

摘要

目的

结直肠癌(CRC)是全球第三大常见癌症,其病因涉及遗传和环境因素的相互作用。新血管通过称为血管生成的过程形成,在恶性肿瘤的生长、进展和转移中起重要作用。血管内皮生长因子(VEGF)是最重要的血管生成因子之一,是血管内皮细胞的特异性有丝分裂原。在本病例对照研究中,我们开展该研究以评估VEGF单核苷酸多态性是否在调节CRC易感性中发挥作用。

方法

我们通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析评估了103例CRC患者和129名健康对照者的VEGF -2578A>C、+936C>T和-460C>T基因型。此外,还进行了单倍型分析。估计比值比(OR)和95%置信区间(CI)。

结果

-2578A>C与CRC风险显著相关(OR 1.81;95%CI 0.94-3.47;p=0.0495),而+936C>T和-460C>T基因型在病例组和对照组中的分布无显著差异。VEGF A2578-T936-T460单倍型可能与CRC的发生有关(OR 8.77;95%CI 1.05-73.36;p=0.0434)。所有八种单倍型均有显著的单倍型效应(p=0.02)。

结论

这些结果表明VEGF多态性可能在CRC的发生中起作用。因此,可能需要进一步研究VEGF多态性,以用于确定CRC的危险因素,并对抗VEGF靶向癌症治疗具有预测价值。

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