| ObjectiveVascular endothelial growth factor (VEGF) is a potent angiogenic mediator, TNF-α(tumor necrosis factor-alpha) has important effects on tumor growth,apotosis and metastasis. The present study is to investigate the relationship between genetic polymorphism of VEGF,TNF-α,haplotypes of VEGF and interleukin-6 polymorphisms and susceptibility to lung cancer in chinese Han nation. Methods-2578C/A,936C/T of VEGF gene,-238 G/A of TNF-agene,-572 G/C of IL-6 gene genotypes were determined by PCR-RFLP method in 150 patients with lung cancer and 150 healthy controls in chinese Han nation, with case-control method.Software PHASE 1.0 was used to construct the haplotypes of VEGF gene and the haplotypes of VEGF gene 936C/T and IL-6 gene-572 G/C.Unconditional logistic regression model was used to analyze the statistical association of genotypes or haplotypes and susceptibility in two groups adjusted by mixed factors.ResultsIndividuals with at least one-2578A allele were at a significantly decreased risk of lung cancer compared with those carrying-2578CC genotype (P=0.001,OR=0.303, 95% CI=0.153-0.601). When analyses were stratified by gender,the combined -2578 CA and AA genotype, were associated with a considerally reduced risk of lung cancer.The distribution of the two haplotypes(936C/-2578C and 936C/-2578A) among overall lung cancer cases were significantly different from that among the controls(P=0.016, OR=0.317,95% CI=0.124-0.809 and P=0.018, OR=0.547,95% CI=0.331-0.903). When the cases were categorized by tumor histology, the distribution of C-C haplotype in the adenocarcinoma(AC) group was associated with a substantially lowered risk of AC(P=0.004, OR=0.237,95% CI=0.090-0.627), compared with the reference haplotypes. For men:individuals with one-2578A allele were at a significantly decreased risk of lung cancer compared with those carrying-2578CC genotype(P=0.001,OR=0.264,95% CI=0.128-0.547). When analyses were stratified by smoking and pathology, the participants without smoking or with squamous cell carcinoma,who carrying the 936C/T genotype were associated with a considerally increased risk of lung cancer. Compared with those carrying-238GG genotype,individuals with-238 G/A were at a significantly increased risk of lung cancer.There was significant difference of-238 G/A polymorphisms in squmous lung cancer,the individuals with-238 G/A genotype will have an increased risk. The distribution of the 936C/-572G haplotype among overall lung cancer cases were significantly different from that among the controls, When the cases were categorized by tumor histology, the distribution of C-G haplotype in the squamous-cell carcinoma group was associated with a substantially lowered risk of AC(P=0.004, OR=0.237,95% CI=0.090-0.627),compared with the reference haplotypes.Conclusion1. VEGF polymorphism may be a critical risk for the genetic susceptibility to lung cancer in chinese Han nation.(1)Individuals with at least one-2578A allele were at a significantly decreased risk of lung cancer compared with those carrying-2578CC genotype.(2)When analyses were stratified by gender,the combined-2578 CA and AA genotype, were associated with a considerally reduced risk of lung cancer.(3)The distribution of the two haplotypes(936C/-2578C and 936C/-2578A) among overall lung cancer cases were significantly different from that among the controls, with a considerally reduced risk of lung cancer.(4) When the cases were categorized by tumor histology, the distribution of C-C haplotype in the adenocarcinoma(AC) group was associated with a substantially lowered risk of AC(P=0.004, OR=0.237,95% CI=0.090-0.627),compared with the reference haplotypes.2. VEGF polymorphism for men in chinese Han nation:(1) Individuals with one-2578A allele were at a significantly decreased risk of lung cancer compared with those carrying -2578CC genotype(P=0.001,OR=0.264,95% CI=0.128-0.547), there were no difference ofAA genotype compare with CC genotype.(2) When analyses were stratified by smoking, individuals with 936CT were at a significantly increased risk of lung cancer compared with those carrying 936CC genotype in non-somkers. In the participants with smoking,there were difference of-2578 position polymorphism, individuals with one mutational gene were at a significantly increased risk of lung cancer compared with wild genotype.(3) Individuals who carrying the 936CT genotype were associated with a considerally increased risk of lung squamous cell cancer, compared with 936CC genotype.There were significant difference of distribution of 2578C/A genotype.The participants with AC,who carrying the-2578 CA genotype were associated with a considerally decreased risk of lung cancer, compared with CC genotype.3. TNF-αpolymorphism may be a critical risk for the genetic susceptibility to lung cancer in chinese Han nation.(1)Compared with those carrying-238GG genotype,individuals with-238 G/A were at a significantly increased risk of lung cancer.(2)There was significant difference of-238 G/A polymorphisms in squmous lung cancer,the individuals with-238 G/A genotype will have an increased risk. 4. The analysis of haplotypes of VEGF gene polymorphism and IL-6 gene polymorphism in chinese Han nation.(1)The distribution of the 936C/-572G haplotype among overall lung cancer cases were significantly different from that among the controls, (2)When the cases were categorized by tumor histology, the distribution of C-G haplotype in the squamous-cell carcinoma group was associated with a substantially lowered risk of AC,compared with the reference haplotypes.
|
PDF Full Text Request