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Study on the Association of VEGF Genetic Polymorphisms with Primary Lung Cancer

Author: YuanJunJian
Tutor: GuoYang
School: Hebei Medical University
Course: Surgery
Keywords: Lung cancer Vascular endothelial growth factor Gene polymorphism Single nucleotide Genetic predisposition Risk of
CLC: R734.2
Type: Master's thesis
Year: 2011
Downloads: 47
Quote: 0
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Abstract


Objective: To become China's first lung malignancies cause of death, accounting for one fifth of all cancer deaths, and the morbidity and mortality continues to rapidly rise. According to information provided by the Ministry of Health, the National Office of Cancer Prevention: the incidence of lung cancer in China increased by 26.9% annually, if not promptly take effective control measures, is expected to lung cancer patients in China will reach 100 million by 2025, to become the world's first lung power. The research shows that: smoking, environmental pollution, occupational exposure, lifestyle adverse and other factors will affect the occurrence of lung cancer, and epidemiological studies have shown there is a close relationship between smoking and lung cancer, smoking causes lung cancer incidence and mortality rates have continued to rise. The study results show that: In cases of death from lung cancer, 80% of men, 75% women with smoking-related. With the continuous advancement of the molecular epidemiology of lung cancer, lung cancer cell and molecular biology research level, the research on the genetic susceptibility of lung cancer direction gradually be taken seriously. The growth and metastasis of malignant tumors rely on a rich supply of nutrients, nutrients and oxygen through the blood vessels in the tissue into tumor cells, metabolites discharged cells, which laid an important foundation for tumor cell growth and migration. Biological characteristics and mechanism study tumor angiogenesis understanding of the occurrence, development, invasion and metastasis of malignant tumors has important theoretical significance and clinical value. Vascular endothelial growth factor (VEGF) is amongst one of the factors that promote angiogenesis, is an the physiological the venereal rational angiogenesis regulators, may act directly on the vascular endothelial cells, promote the growth of human blood vessels in tumor formation, growth, invasion and play an important role in the transfer process. Recent studies have shown that: lung cancer, esophageal cancer, prostate cancer, ovarian cancer, and other patients with neoplastic disease, tumor tissue, blood, urine can be detected in a corresponding increase to the amount of VEGF expression. The human VEGF gene has some highly polymorphic loci, these polymorphic sites may change through the gene sequence, thus changing the transcriptional activity of the gene and thus affect the expression of the corresponding protein, leading to a human individual differences in disease susceptibility. The study showed that the promoter region of the VEGF gene-460T / C,-2578C / A single nucleotide polymorphism (single nucleotide polymorphisms, SNPs) related to the risk of many diseases. The purpose of this study is to explore the VEGF gene promoter region-460T / C,-2578C / A single nucleotide polymorphism (single nucleotide polymorphisms, SNPs) relationship with the Chinese Han population risk of lung cancer, lung cancer further elucidate molecular biology mechanism. Methods: A hospital-based case - control study, collected 251 cases of patients with lung cancer (squamous cell carcinoma 95 cases, 68 cases of adenocarcinoma, 41 cases of small cell lung cancer, glandular prickle cell carcinoma 26 cases, other pathological types (including mucus epidermoid carcinoma, large cell undifferentiated carcinoma, clear cell carcinoma, sarcomatoid carcinoma, bronchioloalveolar carcinoma) the intravenous anticoagulant 5ml of 21 cases and 255 healthy control subjects, at the same time recording medical history and personal information. using protease K digestion - salting out method in peripheral blood collected week to extract the white blood cells of DNA using the polymerase chain reaction - restriction fragment length polymorphism (polymerase chain reaction-restriction the fragment length polymorphism, PCR-RFLP) analysis method and primer mediated restriction polymerase chain reaction (primer-introduced restriction analysis PCR, PIRA-PCR) was used to detect the genotype frequencies of the-460C / T and VEGF-2578C/ASNPs distribution data statistical analysis SPSS13.0 software analysis package (SPSS Company, Chicago, Illinois, USA), P lt; 0.05 was considered statistically significant. comparison you genotype frequency observed value and the expected value of χ ~ 2 test, analysis of parallel Hardy-Weinberg equilibrium. cases group and the control group of age differences in line t test case group and the control group genotype and allele distribution line × list χ ~ 2 test. analysis of VEGF-460C / T and-2578C / A gene EH software haplotype frequencies, 2LD software (1.2 version, Rockefeller University, New York) analysis of linkage disequilibrium. correction of gender, age, and smoking status to non-conditional logistic regression relative risk, odds ratio (odds ratio, OR ) and its 95% confidence interval (confidence interval, CI). Results: VEGF-460T / C and VEGF-2578C / A two single nucleotide polymorphisms (SNPs) in the promoter region of the VEGF gene in a healthy control group The genotypic distribution Hardy-Weinberg equilibrium analysis (P gt; 0.05). 2 in lung cancer patients and healthy control group, smoking the proportion of individuals were 59.8%, 41.6%, the significant difference between the two groups (χ - 2 = 16.748, P lt; 0.01). smoking may significantly increase the risk of lung cancer (OR = 3.103,95% CI = 1.978-4.867) in lung cancer patients and healthy control group, VEGF gene promoter region-460T / C single nucleotide polymorphism the three genotype frequency (T / T, C / T, C / C) were 52.2%, 40.2%, 7.6% and 61.2%, 35.3%, 3.5%, compared between the two groups genotype distribution, there was a significant difference (P = 0.042); allele frequency distribution (T, C) were 72.3%, 27.7% and 78.8%, 21.2%, between the two groups with a significant difference (P = 0.016 ). compared with T / T, C / T genotype, carrying the C / C genotype may significantly increase the incidence of lung cancer risk (OR = 1.979, 95% CI = 1.339-2.925) in lung cancer patients and healthy controls group, the VEGF gene promoter region-2578C / A single-nucleotide polymorphism the three genotype frequency (C / C, C / A, A / A) is 49.8%, 43.0%, 7.2% and 60.4%, respectively. from 36.5% to 3.1%. groups genotype distribution, with a significant difference (P = 0.019); allele frequency distribution (C, A) 71.3% 28.7% 78.6% 21.4%, respectively, between the two groups has significant difference (P = 0.007). compared with the C / C, C / A genotype, portable A / A genotype may significantly increase the incidence of lung cancer risk (OR = 2.044, 95% CI = 1.394-2.994). 5 application 2LD software VEGF-460T / C and -2578 C / A polymorphism loci joint analysis shows that there is no chain imbalance (D '= 0.303717) between the two polymorphic loci. conclusions: 1 smoking can significantly increase the risk of lung cancer. 2 expression of VEGF-460T / C single nucleotide polymorphism associated with the risk of lung cancer, that carry the C allele (C / TC / C), may significantly increase the risk of lung cancer. 3 VEGF-2578C / A single nucleotide polymorphism may significantly increase the risk of lung cancer. 4 of VEGF gene promoter region-VEGF460T / C and -2578 C / A single nucleotide polymorphic loci in linkage not balance.

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CLC: > Medicine, health > Oncology > Respiratory system tumors > Lung tumors
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