| Objective:Lung cancer became the first cause of death of malignant tumour in china,Accounting for the death of the fifth of malignant tumour, which incidence and mortality continues to rise rapidly. According to the ministry of national cancer prevention and control of the office provides information displayed :The lung cancer incidence of our annual growth is 26.9%. As not to take effective measures to control, until 2025, the lung cancer patients in china will reach 1 million, It is expected to become the world's first lung cancer powers country. Research and survey have demonstrated that cigarette smoking, environmental pollution, occupational exposure and bad lifestyle etc factors will influence the occurrence of lung cancer. Epidemiological researches proved that there exists close relationship between smoking and lung cancer. Because of smoking, lung cancer incidence and mortality rate have continued to rise. Research result display:80% of men and 75% of men have related with smoking in lung cancer deaths of cases. Along with the developing of lung cancer molecules epidemiological and cells molecular biology , the effect of hereditary susceptibility was focused on the research of lung cancer.Malignant tumor growth and transfer must be supplied with the nutrients. The nutrients and oxygen of organizations enter the tumor cells by vessels, and metabolic product comes out. From the cells, this creates the important basic conditions for the tumor cells growth and transfer. There is important the meaning and value in clinical application to study biological characteristics and mechanisms of the vessels generation of malignancies in the growth process of malignant neoplasms development aggression and transfer. Vascular endothelial growth factor (VEGF) is a prime regulator of physiological and pathological angiogenesis in known as angiogenic factor.It can directly act on endothelial cell of blood vessel and result in neovascularization. So VEGF is believed to play a central role in the development, growth, invasiveness, and metastasis of tumor. Recently, studies show that some tumors may induce a higher serum, urinary or intratumoral VEGF level, for instance : lung cancer, Esophagus cancer, prostatic carcinoma, and ovarian carcinoma.Some single nucleotide polymorphisms (SNPs) in the promoter regions of human VEGF gene may influence protein expression by altering VEGF gene transcribe activity. Studies have shown that theVEGF-460T/C, -2578C/A polymorphisms were associated with the risk of some diseases. Our purpose was to analysis the association of VEGF-460T/C, -2578C/A SNPs with the susceptibilitiy of lung cancer in North China and further illuminate molecular biology mechanisms of lung cancerMethods: This hospital-based case-control study comprised 251 patients with lung cancer (95 squamous cell carcinomas, 68 adenocarcinomas, 41 small cell lung carcinomas,26 adenosquamous carcinoma,and 21 other pathological types including Mucoepidermoid carcinoma, large cell undifferentiated carcinoma, clear cell carcinoma, sarcomatoid carcinoma, bronchioloalveolar carcinoma, and so on included) and 255 frequency-matched healthy controls with no evidence of disease. Five milliliter of venous blood from each subject was drawn in Vacutainer tubes containing EDTA and stored at 4℃, meanwhile the medical history and personal data of each 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-460T/C and -2578C/A SNPs were analyzed by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method and primer introduced restriction analysis PCR (PIRA-PCR).Statistical analysis was performed using SPSS13.0 software package. A probability level of 5% (P<0.05) was considered significant. Hardy-Weinberg analysis was performed by comparing the observed and expected genotype frequencies in study groups using Chi-square test. The age difference of cases and frequency-matched controls was validated by the t-test. Comparison of the VEGF gene genotype and allelotype distribution in cancer patients and healthy controls was performed by means of two-sided contingency tables using Chi-square test. The VEGF -460T/C and -2578C/A haplotype frequencies and linkage disequilibrium coefficient were estimated by using the EH linkage software and 2LD program, respectively. The odds ratio (OR) and 95% confidence Interval (CI) were calculated by using an unconditional logistic regression model and adjusted by age, gender and smoking status accordingly. Results:1 The distribution of the VEGF-460T/C,-2578C/A genotypes in the control group did not significantly deviate from that expected for a Hardy-Weinberg equilibrium(P﹥0.05)2 The frequency of smokers in lung cancer patients and healthy controls were 59.8%/41.6%, respectively. There was statistically significant difference between the patients and controls(χ~2=16.748 , P <0.01).smoking may increased the risk of developing lung cance(rOR =3.103,95% CI =1.978-4.867)3 The genotype frequencies of the VEGF -460 T/T, C/T and C/C in patients and controls were 52.2%/61.2%, 40.2%/35.3% and 7.6%/3.5%, respectively; the T and C allele frequencies were 72.3%/78.8% and 27.7%/21.2%, respectively. There was statistically significant difference in the genotype distributions or allele frequencies of VEGF -460T/C between the patients and controls (P=0.016). Compared with the T/T+C/T genotypes, the C/C genotype could significantly modify the risk of developing epithelial ovarian cancer. The odds ratio was 1.979 (95% CI=1.339~2.925).4 The genotype frequencies of the VEGF -2578 C/C, C/A and A/A in patients and controls were 49.8%/60.4%, 43.0%/36.5% and 7.2%/3.1%, respectively; the C and A allele frequencies were 71.3%/78.6% and 28.7%/21.4%, respectively. There was statistically significant difference in the genotype distributions or allele frequencies of VEGF -460T/C between the patients and controls (P=0.007). Compared with the C/C+C/A genotypes, the A/A genotype could significantly modify the risk of developing epithelial ovarian cancer. The odds ratio was 2.044 (95% CI=1.394~2.994).5 The combined effect of VEGF -460T/C and -2578C/A SNP on lung cancer was analyzed. It was shown that the two SNPs were not in linkage disequilibrium (D'=0.303717).Conclusions:1 Smoking may increase the risk of developing lung cancer.2 VEGF -460T/C polymorphism was associated with susceptibility to lung cancer, carrying C allele may significantly increase the risk of developing lung cancer.3 VEGF-2578C/A SNP was associated with an increased risk of lung cancer.4 The promoter polymorphisms -460T/Cand the -2578C/A were not linkage disequilibrium. |
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