title: Genetic Variants of VEGF (rs201963 and rs3025039) and KDR (rs7667298, rs2305948, and rs1870377) Are Associated with Glioma Risk in a Han Chinese Population: a Case-Control Study.
abstract: A glioma is the most common type of brain tumor that accounts for nearly 80 % of brain cancers. Vascular endothelial growth factor (VEGF) and its receptor, the kinase insert domain receptor (KDR), are involved in the angiogenesis of cancers. In this study, we investigate whether the polymorphisms of VEGF and KDR are associated with a glioma risk. Blood samples were collected from 477 glioma patients and 477 healthy controls. Five tag-single nucleotide polymorphisms (SNPs) of KDR were obtained from the HapMap database, and eight tag-SNPs of VEGF were selected based on previous studies. After extraction of genomic DNAs by a Qiagen DNA blood kit, the SNPs of VEGF and KDR were genotyped with a Sequenom MassArray iPLEX platform and further analyzed with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. The odds ratios and their 95% confidence interval (95% CI) were used to assess the association between VEGF, KDR polymorphisms, and glioma risks with the aid of SPSS 13.0 software. The haplotype analysis demonstrated that two SNPs of VEGF [rs3025039 (C>T), rs2010963 (G>C)] could elevate the susceptibility to a glioma in the homozygous model [odds ratio (OR) = 3.13 (95% confidence interval (CI) 1.30-7.49, P = 0.007) and OR = 1.58 (95% CI 1.07-2.34, P = 0.022), respectively], dominant model [OR = 1.38 (95% CI 1.04-1.84, P = 0.025) and OR = 1.32 (95% CI 1.01-1.72, P = 0.043), respectively], and allelic model [OR = 1.43 (95% CI 1.11-1.84, P = 0.005) and OR = 1.24 (95% CI 1.04-1.50, P = 0.019), respectively]. Furthermore, three SNPs of KDR [rs7667298 (A>G), rs2305948 (C>T), rs1870377 (T>A)] were also assumed to be associated with an increased risk of a glioma in the homozygous [OR = 1.93 (95% CI 1.30-2.86, P = 0.001), OR = 2.56 (95% CI 1.28-5.11, P = 0.006), and OR = 1.52 (95% CI 1.00-2.31, P = 0.049), respectively], dominant [OR = 1.52 (95% CI 1.16-1.98, P = 0.002), OR = 1.41 (95% CI 1.05-1.87, P = 0.020), and OR = 1.48 (95% CI 1.13-1.93, P = 0.004), respectively], and allele models [OR = 1.39 (95% CI 1.15-1.67, P = 0.001), OR = 1.47 (95% CI 1.14-1.89, P = 0.002), and OR = 1.27 (95% CI 1.05-1.52, P = 0.013), respectively]. The genetic polymorphisms of VEGF [rs3025039 (C>T), rs2010963 (G>C)] and KDR [rs7667298 (A>G), rs2305948 (C>T), rs1870377 (T>A)] increased glioma susceptibility in a Chinese population, suggesting the possibility of VEGF and KDR as genetic markers for glioma. Additional functional and association studies with different ethnic groups included are needed to further confirm our results.
authors.affiliation: Operation Room, Shanghai Children's Medical Center, School of medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
authors.forename: Jiannan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
authors.forename: Shanquan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Operation Room, Shanghai Children's Medical Center, School of medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Guang-Fu Hospital, Jinhua City, Zhejiang Province, 321000, China. jie_8189@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. gejianweiok@hotmail.com.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Ge
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics; D016022:Case-Control Studies; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005910:Glioma / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Genetic markers; Glioma; Han Chinese population; Kinase insert domain receptor; Single nucleotide polymorphism; Vascular endothelial growth factor