Linhares Paulo, Viana-Pereira Marta, Ferreira Mónica, Amorim Júlia, Nabiço Rui, Pinto Filipe, Costa Sandra, Vaz Rui, Reis Rui Manuel
1 Department of Neurosurgery, Hospital S. João, Porto, Portugal.
2 Faculty of Medicine, University of Porto, Porto, Portugal.
Tumour Biol. 2018 Mar;40(3):1010428318766273. doi: 10.1177/1010428318766273.
The vascular endothelial growth factor regulates angiogenesis that is increased in glioma. VEGF polymorphisms are thought to modulate vascular endothelial growth factor plasma levels and therefore may be implicated in glioma risk. We aimed to clarify the role of VEGF and von Willebrand factor polymorphisms in glioma susceptibility and prognosis. A case-control study of 126 glioma patients and 180 cancer-free controls was performed. Using Sequenom MassARRAY platform, 11 VEGF and 1 VWF polymorphisms were genotyped. Unconditional multivariate logistic regression models were used to calculate odds ratios and 95% confidence intervals. The associations between polymorphisms and survival were evaluated using a Cox regression model. Bonferroni's adjustment was used to correct for multiple testing. The VEGF polymorphism rs833061 was strongly associated with increased risk for glioma (odds ratio = 164.85) and glioblastoma (odds ratio = 155.66), confirmed after Bonferroni correction. Also, the VEGF polymorphisms rs3024994, rs2010963, and particularly the homozygous carriers of rs1005230 were associated with a worse prognosis for glioma and glioblastoma. Our data support a role of VEGF and VWF polymorphisms as glioma biomarkers, with additional potential relevance for molecular stratification of patients for anti-angiogenic therapies.
血管内皮生长因子调节神经胶质瘤中增加的血管生成。血管内皮生长因子多态性被认为可调节血管内皮生长因子的血浆水平,因此可能与神经胶质瘤风险有关。我们旨在阐明血管内皮生长因子和血管性血友病因子多态性在神经胶质瘤易感性和预后中的作用。对126例神经胶质瘤患者和180例无癌对照进行了病例对照研究。使用Sequenom MassARRAY平台对11种血管内皮生长因子和1种血管性血友病因子多态性进行基因分型。采用无条件多变量逻辑回归模型计算比值比和95%置信区间。使用Cox回归模型评估多态性与生存率之间的关联。采用Bonferroni校正法校正多重检验。血管内皮生长因子多态性rs833061与神经胶质瘤风险增加(比值比=164.85)和成胶质细胞瘤(比值比=155.66)密切相关,经Bonferroni校正后得到证实。此外,血管内皮生长因子多态性rs3024994、rs2010963,尤其是rs1005230的纯合子携带者与神经胶质瘤和成胶质细胞瘤的预后较差有关。我们的数据支持血管内皮生长因子和血管性血友病因子多态性作为神经胶质瘤生物标志物的作用,对患者进行抗血管生成治疗的分子分层具有额外的潜在相关性。