Study On The Association Of VEGF Genetic Polymorphisms With Non-small Cell Lung Cancer

Objective：Lung cancer accounts for about20%of all the malignanttumor mortality, which is currently the leading cause of cancer deathworldwide, more than80%of which is non small cell lung cancer(NSCLC). According to the WHO released data show: both the incidence(1200000/year) and mortality (1100000/year) of lung cancer ranks thefirst of global cancer, and both of them showed an upward trend year byyear. According to the information provided by the Office of the NationalCancer: since the1970s, the mortality rate of lung cancer in China rosenearly5times. Plenty of research suggests: smoking is closely related tothe pathogenesis of lung cancer, smoker incidence of lung cancer almost10times higher than non-smokers. With the continuous progress ofresearch of molecular biology of lung cancer, the study of the genetic levelon NSCLC is also increasing.Study found NSCLC with high malignant degree, poor prognosis,easy early invasive metastasis and other biological characteristics areassociated with vascular endothelial growth factor (VEGF). VEGF is animportant regulator of angiogenesis, have a strong stimulating effect onthe proliferation of endothelial cells, participate in the formation of newblood vessels and lymphatic vessels. In recent years, many studies haveshown that VEGF is involved in the process of tumor formation,development, invasion and metastasis. And the invasion and metastasis isthe main cause of failure of the malignant tumors treatment.In2010, according to a study of onset age in1185patients with lungcancer showed that: the average age was about63years old, the majorityof patients over40, and the incidence rate increased with age, the male tofemale ratio was3.41:1, lower than the40,the proportion of female patient with lung cancer was higher than that of male. This study aimed toinvestigate the relationship between the VEGF gene in the promoterregion of the-460C/T,-2578A/C single nucleotide polymorphism (SNPs)and the onset risk of lung cancer of Chinese Han population aged over40by a case-control experiment.Methods: This study comprised407patients with NSCLC as theexperimental group and270healthy volunteers as control group, each ofthem aged over40.5ml of fasting peripheral blood was drawn from eachsubject, Genomic DNA was isolated from whole blood of two groups byusing proteinase K digestion-saturated sodium chloride salting outextraction. The genotypes of the VEGF-460C/T and-2578A/C SNPs wereanalyzed by PCR-RFLP and PIRA-PCR. Statistical analysis wasperformed by using SPSS16.0software package. P<0.05was consideredsignificant.Results:1The frequency of smokers in the experimental group and controlgroup were56.0%and14.8%, there was statistically significantdifferences between two groups(P＜0.01). Smoking may increase the riskof NSCLC（OR=3.781，95%CI=2.805-5.098).2The frequency of family history in the experimental group andcontrol group were6.4%and8.5%, there was no statistically significantdifference between two groups（χ2=1.097，P=0.295）. Family history hasno relevance with the risk of NSCLC(OR=0.750，95%CI=0.437-1.286).3Three basic genotype frequencies the VEGF-460C/T（T/T、C/T、C/C）in the experimental group and control group were55.8%、39.1%、5.2%and56.3%、38.1%、5.6%,there was no statistically significantdifference between two groups（P=0.955）, VEGF-460T/C SNPs has norelevance with the risk of NSCLC.4Three basic genotype frequencies the VEGF-2578A/C（C/C、A/C、A/A）in the experimental group and control group were56.0%、39.1%、4.9%and73.3%、23.7%、3.0%,there was statistically significant difference between two groups（P＜0.01）.And there was statisticallysignificant difference between the C/C and A/C genotypes（χ2=19.221，P＜0.01）, but no statistically significant difference between the C/C andA/A genotypes（χ2=3.399，P=0.065）.Compared with the C/C genotypes,the A/C genotype could increase the risk of NSCLC(OR=1.682，95%CI=1.318-2.147）.5Classified according to the tumor size, pathology type, lymph nodemetastasis, stage of NSCLC, three basic genotype frequencies theVEGF-2578A/C （C/C、 A/C、 A/A） were no statistically significantdifference(P=0.786、P=0.550、P=0.851、P=0.655). VEGF-2578A/C SNPshas no relevance with the tumor size, pathology type, lymph nodemetastasis, stage of NSCLC.Conclusions:1Smoking could increase the risk of NSCLC, but family historynone.2VEGF-2578A/C SNPs was associated with an increased risk ofNSCLC, the A/C genotype could increase the risk of NSCLC. But VEGF-460C/T SNPs none.3VEGF-2578A/C SNPs has no relevance with the tumor size,pathology type, lymph node metastasis, stage of NSCLC.