title: VEGFA and VEGFR2 genetic polymorphisms and survival in patients with diffuse large B cell lymphoma.
abstract: 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.
authors: Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.
authors: Min Kyoung
authors: MK
authors: Kim
authors: Cheolwon
authors: C
authors: Suh
authors: Hyun Sook
authors: HS
authors: Chi
authors: Hee Soon
authors: HS
authors: Cho
authors: Young Kyung
authors: YK
authors: Bae
authors: Kyung Hee
authors: KH
authors: Lee
authors: Gyeong-Won
authors: GW
authors: Lee
authors: In-Suk
authors: IS
authors: Kim
authors: Hyeon-Seok
authors: HS
authors: Eom
authors: Sun-Young
authors: SY
authors: Kong
authors: Sung Hwa
authors: SH
authors: Bae
authors: Hun Mo
authors: HM
authors: Ryoo
authors: Im-Hee
authors: IH
authors: Shin
authors: Yeung-Chul
authors: YC
authors: Mun
authors: Hwasoon
authors: H
authors: Chung
authors: Myung Soo
authors: MS
authors: Hyun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*; D055815:Young Adult
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2