title: Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer.
abstract: Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. DNA sequence variations in the vascular endothelial growth factor (VEGF) gene may lead to altered VEGF production and/or activity, thereby causing interindividual differences in the susceptibility to lung cancer via their actions on the pathways of tumor angiogenesis. To test this hypothesis, we investigated the potential association between three VEGF polymorphisms (-460T > C, +405C > G, and 936C > T)/haplotypes and the risk of lung cancer in a Korean population. VEGF genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency matched for age and sex. VEGF haplotypes were predicted using Bayesian algorithm in the phase program. Compared with the combined +405 CC and CG genotype, the +405 GG genotype found associated with a significantly decreased risk of small cell carcinoma [SCC; adjusted odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.17-0.78]. The 936 CT genotype and the combined 936 CT and TT genotype were also associated with a significantly decreased risk of SCC compared with the 936 CC genotype (adjusted OR, 0.47; 95% CI, 0.26-0.85 and adjusted OR, 0.44; 95% CI, 0.24-0.80, respectively). Haplotype CGT was associated with a significantly decreased risk of SCC (adjusted OR, 0.39; 95% CI, 0.18-0.87), whereas haplotype TCC conferred a significantly increased risk of SCC (adjusted OR, 1.63; 95% CI, 1.14-2.33). None of the VEGF polymorphisms studied significantly influenced the susceptibility to lung cancer except SCC. However, haplotypes TCT and TGT were significantly associated with the risk of overall lung cancer, respectively (adjusted OR, 0.38; 95% CI, 0.25-0.60 and adjusted OR, 3.94; 95% CI, 2.00-7.76, respectively). These effects of haplotypes TCT and TGT on lung cancer risk were observed in three major histologic types of lung cancer. These results suggest that the VEGF gene may be contribute to an inherited predisposition to lung cancer.
authors.affiliation: Department of Biochemistry, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea.
authors.forename: Su Jeong
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sin Yeob
authors.initials: SY
authors.lastname: Lee
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Park
authors.forename: Jin Sung
authors.initials: JS
authors.lastname: Jang
authors.forename: Ga Young
authors.initials: GY
authors.lastname: Lee
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Son
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.forename: Sin
authors.initials: S
authors.lastname: Kam
authors.forename: Rang Woon
authors.initials: RW
authors.lastname: Park
authors.forename: Tae-In
authors.initials: TI
authors.lastname: Park
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Jung
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007723:Korea; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016017:Odds Ratio; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A