| Objective：Carcinoma of the lung is the most common cause of death due tocancer in both men and women. The lung cancer produces the seriousinfluence on the mankind’s life health and life quality since20th century.The morbidity and mortality of lung cancer have risen sharply because ofenvironmental deterioration, occupational exposure and tobacco productuse.The lung cancer is thought to be a kind of extremely rare disease inthe beginning of last century, but more than1.5million new cases of lungcancer are diagnosed annually all over the world. Our country’s lungcancer death rate has already risen to17.27/100000, which made itexceed esophageal cancer, hepatocellular carcinoma, gastric cancer andcervical cancer. Carcinoma of the lung has become to the leading diseaseof cancer mortality. According to the of epidemiology, the use of tobaccoconstitutes the greatest risk factor in the development of lung carcinoma,the morbidity of smokers is10times higher than non-smokers, but only asmall fraction of smokers develop to lung cancer,which suggests thatgenetic factors contribute to lung cancer risk. Along with the progress ofepidemiology and molecular biology, research on genetic susceptibility oflung cancer has gradually taken people’s attention.The formation of new capillaries are essential to the proliferation oftumor、the invasion and metastasis of malignant tumors. It can ensure thenutritional supplements of cancer cells. The study found that,there aremore than30kinds of growth factors which relate to the angiogenesis oftumor, for example, vascular endothelial growth factor、angioinhibin、fibrin growth factor and so on. VEGF (vascular endothelial growth factor,VEGF) is a specific mitogen of endothelial cell, it has specific effects to vascular endothelial cells and promote endothelial cell division,proliferation and migration. VEGF plays a key role in tumor angiogenesisprocess. The recent study shows that the growth of new blood vessels isclosely related to the biological behavior of VEGF. The growth of lungcancer’s new blood vessels are often accompanied with the highexpression of VEGF, the expression of VEGF in lung tissues wassignificantly higher than in normal tissue, it also one of the importantindicators to determine the prognosis of lung cancer.Human VEGF gene is located on chromosome6p21.3with7introns and8exons, length28kb. Study found that the polymorphism ofVEGF gene is related to lung cancer. This study uses a case-controlmethods to explore the relationship between single nucleotidepolymorphisms (single nucleotide polymorphism, SNP) of VEGF geneVEGF-1154G/A and405G/C with the risk of lung cancer in Hanpopulation.Methods:In this study, we used the rigorous case-control experiment. Weselected cases between2003to2013from the Fourth Hospital of HebeiMedical University, all patients were confirmed by postoperativePathology with primary non-small cell lung cancer. Including291casesof male,116cases of female, with an average age of60.26years old, atotal of407cases. Control group including158cases of male,112casesof female, with an average age of59.55years old, a total of270cases.5ml peripheral blood was exsanguinated and record history and allrelevant information. The DNA was extracted using proteinase Kdigestion-salting method within a week. We detected the genotypefrequency distribution of VEGF-1154G/A and VEGF+405G/C SNPs bythe method of Polymerase chain reaction-restriction fragment lengthpolymorphism (PCR-RFLP) analysis and primer-mediated polymerasechain reaction restriction (PIRA-PCR). All the experimental data wasanalysised using SPSS16.0statistical package. When P<0.05,we determined that the difference was statistically significant.Results:1Age distribution between the experimental group and the controlgroup distribution by one-way ANOVA test statistic found no significantdifferences (χ2=81.222, P=0.340).2The number of smokers in the experimental group was228, thenumber of smokers in the control group was40, the frequency of themwere56.0%/14.8%,there was significant difference between the twogroups difference (P=0.000). This shows that smoking increases the riskof lung cancer in the population; family history was no significantdifference (χ2=1.126, P>0.05) between the patients in the experimentalgroup and the healthy control group.3The genotype frequencies of VEGF-1154G/A GG, AG, AA in theexperimental group and control group were69.8%,28.0%,2.2%and71.5%,25.9%,2.6%, respectively. There was no statistically significantdifference in the distribution of genotypes (P=0.808), it meaned thatVEGF-1154G/A polymorphism had no correlation with the incidence ofnon-small cell lung cancer.4VEGF+405G/C GG, CG, CC in the experimental group and thecontrol group were25.1%,45.3%,29.6%and39.6%,48.3%,12.2%, χ2=21.944, P <0.01, it illustrated the difference between the two groups wasstatistically significant. The comparison between GG, CG showed thatCG genotype significantly increased the risk of non-small cell lungcancer (OR value of1.174,95%CI1.013-1.361); The comparisonbetween GG, CC showed that, CC genotype significantly increased therisk of non-small cell lung cancer (OR value of1.924,95%CI1.412-2.620), which also showed that the GG genotype of the normalpopulation can reduce the risk of non-small cell lung cancer.When thethree genotypes of VEGF+405G/A were stratified by tumor size,histological type, lymph node metastasis, stage, tumor staging, nosignificant difference was found in tumor size and the distribution of genotypes (χ2=0.193, P>0.05); no significant difference was found inpathological type and three genotypes (χ2=7.990, P>0.05); thedifference between lymph node metastasis staging with genotypedistribution was not statistically significant (χ2=4.514, P>0.05); therewas no significant difference between tumor staging to the distribution ofthree genotypes(χ2=2.971, P>0.05).5When the overall lung cancer cases were categorized by smokingstatus, three genotypes VEGF+405G/A stratified analysis found: therewere no significant difference between smoking history to genotypedistribution (χ2=2.786, P>0.05); there were significant differencebetween non-smoker to genotype distribution (χ2=21.443, P <0.05),when compared GG with CC, we found that CC significantly increasedthe risk of non-small cell lung cancer with the non-smoker patients.Conclusion:1Smoking can significantly increase the risk of lung cancer, itwas not dependented on the genotype of VEGF+405G/C.2The distribution of VEGF-1154G/A no statistical significancebetween the experimental group to the healthy group, andVEGF-1154G/A could not increase the risk of lung cancer.3VEGF405G/C single nucleotide polymorphisms increase therisk of lung cancer, CC genotype significantly increased the risk ofnon-small cell lung cancer.4There was no significant difference between geno distribution ofVEGF+405G/A to tumor size, pathological type, lymph node metastasisstaging, tumor stage. |
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