The
vascular endothelial growth factor (
VEGF) is a major mediator of angiogenesis involving
tumor growth and
metastasis. Polymorphisms in the
VEGF gene may regulate
VEGF production. In this case-control study, we investigated whether functional polymorphisms (+405 C > G and +936 C > T) in the
VEGF gene are associated with the risk of
lung cancer. Genomic
DNA was isolated from the blood of 100
lung cancer patients and 150 healthy controls, and total
RNA was isolated from 48
tumor tissues and adjacent normal lung tissues. Two
DNA polymorphisms (+405 C > G and +936 C > T) in the 3'-untranslated regions (3'-UTR) and 5'-untranslated regions (5'-UTR) of
vascular endothelial growth factor A (VEGFA) were studied using PCR-RFLP method, and
mRNA expression of VEGFA was studied by quantitative real-time PCR. Polymorphisms in the 5'-UTR (+405 C > G) and 3'-UTR (+936 C > T) did not show significant difference between
lung cancer cases and control samples (P = 0.11 and P = 0.09, respectively).
VEGF +405 CG and GG are significantly more in age group >50 years old, in all grades, and in early pathological stages (P = 0.04, P = 0.03, and P = 0.006, respectively). Also, increased expression of VEGFA
mRNA was noted in tumorous compared to non-tumorous tissue (P < 0.0001). Overexpression of the gene was considered at ΔC (T) > 6.0. Within the group of patients with conventional
tumor, those with histology other than
squamous cell carcinoma (SCC) had a higher level of VEGFA
mRNA expression than SCC patients (P = 0.04). Overexpression of VEGFA
mRNA was noted in
lung cancer and more so in
lung cancer with
adenocarcinoma and
large cell carcinoma histology and in pathological stages III and IV. VEGFA +405 C > G SNP showed an association with age, pathological grade, and stage.