Study On The Association Of Snps Of Vegf Gene With The Risk Of Epithelial Ovarian Cancer

Objective:Ovarian cancer is one of the three most common malignant gynecologic neoplasm. Early ovarian cancer is a silent and often asymptomatic disease. Many patients diagnosed with epithelial ovarian cancer have advanced disease. The overall 5-year survival rate for ovarian cancer is 30%. It is the leading cause of death from gynecologic cancer. The causes of ovarian cancer are poorly understood, but angiogenesis has been associated with the disease. Angiogenesis is an essential process in the development, growth and metastasis of malignant tumors, including ovarian cancer. A key mediator in angiogenesis is vascular endothelial growth factor (VEGF). VEGF is a major angiogenic factor involved in a number of pathologic processes, including neovascularization, a crucial step in the development of solid malignancies. At least 30 single nucleotide polymorphisms (SNPs) exist in the VEGF gene. Among them, the two VEGF polymorphisms (-1154G/A and -460C/T) have been reported to affect the expression of the gene and indicated to be involved in the development of diseases. The aim of this study was to investigate the association of polymorphisms in the VEGF gene with the susceptibility to epithelial ovarian cancer.Methods: This case-contral study included 303 patients with epithelial ovarian cancer and 303 frequency-matched healthy control women. Five milliliter of venous blood from each subject was drawn in Vacutainer tubes containing EDTA and stored at 4℃, while the information of every subject was obtained. The genomic DNA was extracted within one week after bleeding by using proteinase K digestion followed by a salting out procedure. Genotypes of the VEGF-1154G/A, -460C/T genes were analyzed by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis was performed using SPSS11.5 software package. A probability level of 5% was considered significant. The age difference of cases and frequency-matched controls was analyzed by the t-test. Hardy-Weinberg analysis was performed by comparing the observed and expected genotype frequencies in study groups using Chi-square test. Comparison of the VEGF genotype and allelotype distribution in patients and healthy controls was performed by means of two-sided contingency tables using Chi-square test. The odds ratio (OR) and 95% confidence Interval (CI) were calculated using an unconditional logistic regression model.Results:1. The distribution of the VEGF -1154G/A , -460C/T genotypes in the control group did not significantly deviate from that expected for a Hardy-Weinberg equilibrium (P>0.05).2. The genotype frequencies of the VEGF -460 C/C, C/T and T/T in patients and controls were 4.0%/5.6%, 30.7%/31.4% and 65.3%/63.0%, respectively; the C and T allele frequencies were 19.3%/21.3% and 80.7%/78.7%, respectively. There was no statistically significant difference in the genotype distributions or allele frequencies of VEGF -460C/T between the patients and controls (P>0.05; Table 1). Compared with the C/T+T/T genotypes, the C/T genotype could not significantly modify the risk of developing epithelial ovarian cancer. The odds ratio was 1.11 (95% CI=0.79~1.54).3. The genotype frequencies of the VEGF -1154 A/A, G/A, and G/G in patients and controls were 1.7%/2.3%, 17.8%/26.1% and 80.5%/71.6%, respectively; the A and G allele frequencies were 10.6%/15.3% and 89.4%/84.7%, respectively. There was significant difference in genotype and allele distributions of the VEGF -1154G/A between two groups (P=0.037, 0.013, respectively) (Table 3). Compared with the G/A+ A/A genotypes, the G/G genotype significantly increased the risk of developing epithelial ovarian cancer. The odds ratio was 1.64 (95% CI=1.12~2.39) (Table 4).4. The promoter polymorphisms -1154G/A and the -460C/T was not linkage disequilibrium (D'=0.426).Conclusions:1. VEGF -1154G/A polymorphism was associated with susceptibility to epithelial ovarian cancer, carrying G allele may significantly increase the risk of developing epithelial ovarian cancer.2. No significant association of the -460C/T polymorphism with the risk of developing epithelial ovarian cancer.3. The promoter polymorphisms -1154G/A and the -460C/T were not linkage disequilibrium.