Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer.
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.
Lee
Su Jeong
SJ
Department of Biochemistry, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea.
Lee
Sin Yeob
SY
Jeon
Hyo-Sung
HS
Park
Sun Ha
SH
Jang
Jin Sung
JS
Lee
Ga Young
GY
Son
Ji Woong
JW
Kim
Chang Ho
CH
Lee
Won Kee
WK
Kam
Sin
S
Park
Rang Woon
RW
Park
Tae-In
TI
Kang
Young Mo
YM
Kim
In-San
IS
Jung
Tae Hoon
TH
Park
Jae Yong
JY
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*
D042461:Vascular Endothelial Growth Factor A