title: Genetic Variations of Kinase Inserts Domain Receptor (KDR) Gene Are Associated with the Risk of Astrocytomas.
abstract: Astrocytomas is one of the most common central nervous system (CNS) tumors with high mortality rate. Kinase insert domain receptor (KDR) is involved in the regulation of tumor angiogenesis, migration, and vascular permeability. The aim of the study was to explore the relationship between KDR polymorphisms and risk of astrocytomas. Blood samples were collected from 157 astrocytomas patients and 160 healthy controls. Three tag-SNPs (rs2071559C/T, rs2305948T/C, and rs1870377A/T) were identified from the International HapMap Project Databases and genotyped using the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We evaluated the astrocytomas risk caused by individual SNPs and haplotype using odds ratios (ORs) and their 95 % confidence intervals (CIs). In the overall individual SNP analysis, the C allele of rs2071559 was correlated with an increased risk of astrocytomas. However, individuals with mutant allele A and genotype TA + AA of rs1870377 showed a protective effect against astrocytomas. Subgroup analysis based on WHO tumor grade revealed that the C allele of rs2071559 had more influence with the risk of astrocytomas in the grade III-IV (OR = 1.91) subgroup than the grade I-II (OR = 1.47) group. Genotype TT of rs2305948 was found to be significantly associated with susceptibility of astrocytomas only in the grade III-IV subgroup. The protective effect of rs1870377 did not reveal significant difference between the grade III-IV and grade I-II subgroups. Meanwhile, stratified analysis demonstrated that mutation of rs2071559 and rs2305948 could elevate the risk of astrocytomas more significantly in the subgroup of smokers than the nonsmokers. Interestingly, the protective effect of rs1870377 was more obvious in the nonsmokers than the smokers. Additionally, haplotype-specific analysis showed that haplotype CCT and CTT were related with an increased risk of astrocytomas. We found that individual with variants of rs2071559*C and rs2305948*T might significantly elevate the risk of astrocytomas, while mutants of rs1870377*A was associated with the decreased risk of astrocytomas. Further studies about ethnically diverse populations with larger sample size should be performed to confirm the correlation between KDR gene polymorphisms and risk of astrocytomas.
authors.affiliation: Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of ICU, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
authors.forename: Piyong
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
authors.forename: Yichun
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Surgery, China-Japan Union Hospital of Jilin University, #126 Sendai Street, Changchun, 130033, China. jy7555@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Astrocytomas; Genetic association; Haplotype; KDR; Single nucleotide polymorphisms