Diao Lan-Ping, Yu Xiao-Ming, Gao Yu-Huan, Li Yan, Liu Hai-Sheng, Liu Li-Hong, Zhou Rong-Miao, Wang Na, Wu Li-Li, Wang Shi-Jie
Department of Hematology, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, China.
J Cancer Res Clin Oncol. 2009 Nov;135(11):1473-81. doi: 10.1007/s00432-009-0650-0. Epub 2009 Aug 1.
Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and cancer progression. The VEGF genetic polymorphisms were shown to be independently associated with an adverse outcome in various malignancies. We investigated the possible associations of two polymorphisms (-2578C/A and +936C/T) in the VEGF gene with the clinicopathologic parameters for patients with non-Hodgkin's lymphoma (NHL).
We studied the genotype and allele frequencies of the -2578C/A and +936C/T polymorphism in DNA samples of 431 patients with NHL using restriction fragment length polymorphism typing analysis.
The -2578A allele was significantly associated with less frequent clinical staging III, IV and bone marrow involvement (The odds ratio (OR) 0.59; 95% confidence interval (CI) 0.43-0.82; and OR 0.66; 95% CI 0.48-0.91, respectively). The CA and CA + AA genotype of the -2578C/A were significantly associated with less frequent bone marrow involvement than CC genotypes (OR 0.57; 95% CI 0.38-0.86; and OR 0.57; 95% CI 0.39-0.85, respectively). The TT genotype of the +936C/T polymorphism was significantly associated with less frequent T cell histological type, clinical staging III, IV and bone marrow involvement (OR 0.25; 95% CI 0.07-0.89; OR 0.37; 95% CI 0.15-0.89; and OR 0.31; 95% CI 0.10-0.96, respectively). The +936 T allele was marginally associated with less frequent bone marrow involvement and with Clinical staging III, IV (OR 0.71; 95% CI 0.49-1.01; and OR 0.70; 95% CI 0.49-1.00, respectively). None of the evaluated genotypes of -2578C/A was significantly associated with the gender, age, tumor size, B symptoms and immunohistological subtype. No significant associations between the genotype of +936C/T and the clinicopathologic variables, gender, age, tumor size and B symptoms were ascertained. Both of the -2578C/A and +936C/T polymorphisms were not related to the patients' overall survival.
We present the first data on VEGF gene polymorphisms in NHL. Our findings support the hypothesis that the -2578 CA and CA + AA and +936 TT VEGF genotypes and -2578A and +936T alleles are associated with decreased risk for invasion. But the investigated VEGF gene polymorphisms were not associated with prognosis in patients with NHL.
血管内皮生长因子(VEGF)在肿瘤血管生成和癌症进展中起重要作用。VEGF基因多态性已被证明与多种恶性肿瘤的不良预后独立相关。我们研究了VEGF基因中的两种多态性(-2578C/A和+936C/T)与非霍奇金淋巴瘤(NHL)患者临床病理参数之间的可能关联。
我们使用限制性片段长度多态性分型分析研究了431例NHL患者DNA样本中-2578C/A和+936C/T多态性的基因型和等位基因频率。
-2578A等位基因与临床分期III、IV期及骨髓受累频率较低显著相关(优势比(OR)分别为0.59;95%置信区间(CI)0.43 - 0.82;以及OR 0.66;95% CI 0.48 - 0.91)。-2578C/A的CA和CA + AA基因型与骨髓受累频率低于CC基因型显著相关(OR分别为0.57;95% CI 0.38 - 0.86;以及OR 0.57;95% CI 0.39 - 0.85)。+936C/T多态性的TT基因型与T细胞组织学类型、临床分期III、IV期及骨髓受累频率较低显著相关(OR分别为0.25;95% CI 0.07 - 0.89;OR 0.37;95% CI 0.15 - 0.89;以及OR 0.31;95% CI 0.10 - 0.96)。+936T等位基因与骨髓受累频率较低以及临床分期III、IV期有边缘性关联(OR分别为0.71;95% CI 0.49 - 1.01;以及OR 0.70;95% CI 0.49 - 1.00)。-2578C/A的所有评估基因型均与性别、年龄、肿瘤大小、B症状和免疫组织学亚型无显著关联。未确定+936C/T基因型与临床病理变量、性别、年龄、肿瘤大小和B症状之间存在显著关联。-2578C/A和+936C/T两种多态性均与患者的总生存期无关。
我们提供了关于NHL中VEGF基因多态性的首批数据。我们的研究结果支持以下假设:-2578 CA和CA + AA以及+936 TT的VEGF基因型和-2578A和+936T等位基因与侵袭风险降低相关。但所研究的VEGF基因多态性与NHL患者的预后无关。