Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.
Cancer Sci. 2012 Mar;103(3):497-503. doi: 10.1111/j.1349-7006.2011.02168.x. Epub 2012 Jan 9.
We evaluated the impact of functional polymorphisms in the vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor 2 (VEGFR2) genes on the survival of patients with diffuse large B cell lymphoma (DLBCL). Five potentially functional polymorphisms in the VEGFA (rs699947, rs2010963 and rs3025039) and VEGFR2 (rs1870377 and rs2305948) genes were assessed in 494 DLBCL patients treated with rituximab plus CHOP chemotherapy. The associations of genotype and haplotype with overall survival (OS) and progression-free survival (PFS) were analyzed. Of the five polymorphisms, VEGFR2 rs1870377T>A was significantly associated with both OS and PFS; in the dominant model, patients with the AA + TA genotypes had significantly better OS (P = 0.002) and PFS (P = 0.004) than those with the TT genotype. The association between significantly better OS and the AA + TA genotypes was observed separately in patients with low (0-2; P = 0.035) and high (3-5; P = 0.043) International Prognostic Index scores. Multivariate analysis showed that, relative to the AA + TA genotypes, the TT genotype was an independent prognostic factor for poor OS (HR, 1.71; 95% CI, 1.21-2.43; P = 0.002) and PFS (HR, 1.57; 1.13-2.17; P = 0.004). Other independent significant predictors of survival in patients with DLBCL were International Prognostic Index score, age > 60 years, lactate dehydrogenase concentration >normal, extranodal disease >1 and presence of B symptoms. The VEGFR2 rs1870377 polymorphism might affect survival in patients with DLBCL, suggesting that angiogenesis might be related to poor survival in these patients.
我们评估了血管内皮生长因子 A（VEGFA）和血管内皮生长因子 2（VEGFR2）基因中的功能多态性对弥漫性大 B 细胞淋巴瘤（DLBCL）患者生存的影响。在接受利妥昔单抗联合 CHOP 化疗的 494 例 DLBCL 患者中，评估了 VEGFA（rs699947、rs2010963 和 rs3025039）和 VEGFR2（rs1870377 和 rs2305948）基因中 5 个潜在的功能多态性。分析了基因型和单倍型与总生存（OS）和无进展生存（PFS）的关系。在这 5 个多态性中，VEGFR2 rs1870377T>A 与 OS 和 PFS 均显著相关；在显性模型中，AA+TA 基因型患者的 OS（P=0.002）和 PFS（P=0.004）明显优于 TT 基因型患者。在国际预后指数评分较低（0-2；P=0.035）和较高（3-5；P=0.043）的患者中，OS 与 AA+TA 基因型显著相关。多变量分析显示，与 AA+TA 基因型相比，TT 基因型是 OS（HR，1.71；95%CI，1.21-2.43；P=0.002）和 PFS（HR，1.57；1.13-2.17；P=0.004）不良的独立预后因素。DLBCL 患者生存的其他独立显著预测因素包括国际预后指数评分、年龄>60 岁、乳酸脱氢酶浓度>正常、结外疾病>1 和存在 B 症状。VEGFR2 rs1870377 多态性可能影响 DLBCL 患者的生存，提示血管生成可能与这些患者的不良生存有关。
