Sciacca Francesca L, Ciusani Emilio, Silvani Antonio, Corsini Elena, Frigerio Simona, Pogliani Simona, Parati Eugenio, Croci Danilo, Boiardi Amerigo, Salmaggi Andrea
National Neurological Institute C. Besta, Milan, Italy.
Clin Cancer Res. 2004 Feb 15;10(4):1312-7. doi: 10.1158/1078-0432.ccr-03-0198.
Deep venous thrombosis/pulmonary embolism (DVT/PE) is a frequent complication in the course of cancer, particularly in brain tumors. We investigated genetic and plasma factors possibly associated with risk of DVT/PE in patients with high-grade glioma.
In a case-control study, we studied polymorphisms of the genes coding for factor II (G20210A), factor V (G1691A), methylenetetrahydrofolate-reductase (C677T), tissue-type plasminogen activator (tPA; insertion/deletion), plasminogen activator inhibitor-1 (PAI-1; 4G/5G), and vascular endothelial growth factor (VEGF; C936T). We also measured plasma levels of D-dimer, lipoprotein (lp) (a), homocysteine, VEGF, tPA, and PAI-1, comparing healthy control patients with patients with glioma or with patients with neurological nonneoplastic disease (multiple sclerosis).
Genotype frequencies of polymorphisms analyzed were similar in patients with glioma and in healthy matched population. D-dimer, lp (a), homocysteine, VEGF, tPA, and PAI-1 plasma levels were significantly higher in patients with glioma than in healthy controls, whereas patients having neurological nonneoplastic disease had plasma values of these molecules not significantly different from healthy controls. VEGF, tPA, and PAI-1 were also found at high-plasma levels in patients carrying genotypes that, in healthy controls, were associated with "low-producing" phenotypes.
Genetic risk factors alone did not explain the high incidence of DVT/PE observed in patients with glioma. Higher plasma levels of molecules influencing the coagulation pathways indicate that the tumor itself might confer an increased risk of DVT/PE; thus, D-dimer, homocysteine, lp (a), VEGF, tPA, and PAI-1 look like good candidates to be evaluated as DVT/PE prognostic factors.
深静脉血栓形成/肺栓塞（DVT/PE）是癌症病程中常见的并发症，尤其是在脑肿瘤患者中。我们研究了可能与高级别胶质瘤患者发生DVT/PE风险相关的遗传和血浆因素。
在一项病例对照研究中，我们研究了编码凝血因子II（G20210A）、凝血因子V（G1691A）、亚甲基四氢叶酸还原酶（C677T）、组织型纤溶酶原激活剂（tPA；插入/缺失）、纤溶酶原激活剂抑制剂-1（PAI-1；4G/5G）和血管内皮生长因子（VEGF；C936T）的基因多态性。我们还测量了D-二聚体、脂蛋白（a）、同型半胱氨酸、VEGF、tPA和PAI-1的血浆水平，将健康对照患者与胶质瘤患者或神经非肿瘤性疾病（多发性硬化症）患者进行比较。
胶质瘤患者与健康匹配人群中分析的多态性基因型频率相似。胶质瘤患者的D-二聚体、脂蛋白（a）、同型半胱氨酸、VEGF、tPA和PAI-1血浆水平显著高于健康对照，而患有神经非肿瘤性疾病的患者这些分子的血浆值与健康对照无显著差异。在携带某些基因型的患者中也发现VEGF、tPA和PAI-1的血浆水平较高，而在健康对照中，这些基因型与“低产生”表型相关。
仅遗传危险因素并不能解释胶质瘤患者中观察到的DVT/PE高发病率。影响凝血途径的分子血浆水平升高表明肿瘤本身可能增加DVT/PE的风险；因此，D-二聚体、同型半胱氨酸、脂蛋白（a）、VEGF、tPA和PAI-1似乎是作为DVT/PE预后因素进行评估的良好候选指标。
