Study On The Polymorphisms Of MDM2 Gene Associated With Lung Cancer

Lung cancer is one of the most common malignant tumor,it account for 17%of the death of malignant tumor.Early diagnosis and early treatment are the key to enhance the survival of lung cancer.Except for the smoking,the effect of susceptibility was focused on the study of lung cancer.The development of molecular biology make it possible that we can detect suscepbility of lung cancer by using these markers.It will be beneficial to the treatment of lung cancer.The present study has been focused on identifying the candidate SNPs on MDM2 gene case-control analysis.Technique route was followed in such a way that from positive region determined by genome scanning to gene map, and SNP-based LD map.2 SNPs were chosen by accessing the databases at http://www.ncbi.nlm.nih.gov/,http://www.ncbi.nlm.nih.gov/SNP and http://snp. cshl.org/web sites in this region.SNPs were genotyped using PCR-based RFLP analysis.Genotyping data were put into the SPSS database.The Hardy-Weinberg(H-W)equilibrium was tested for genotype frequency distributions of SNPs using the goodness of fit test.To elucidate genetic heterogeneity,in addition,non-small cell lung cancer patients were sub-grouped based on their clinical symptoms and their genetic association with SNPs and clinical subgroups were then analyzed.The following are the details of methodology and major results obtained in this study.1.The H-W equilibrium The goodness of fit test showed that genotype frequency distributions of 2 SNPs were not deviated from the H-W equilibrium,and thus this sample pool was suitable for the genetic analysis.2.Association between genotype and allele of SNPs and non-small cell lung cancer2.1 Association between genotype of SNPs and non-small-cell lung cancerBecause genotype frequency distributions of 2 SNPs were in the H-W equilibrium,we were able to analyze symptoms versus genotypic frequency of each SNP using a case-control design.We found that the frequency of G/G genotype of MDM2SNP1 is higher significantly in NSCLC than that of control (X~2=58.99,P＜0.001).These results suggeste that MDM2 SNP1 associated with the susceptibility of non-small-cell lung cancer.2.2 Association between allele of SNPs and non-small-cell lung cancerBecause allele frequency distributions of 2 SNPs were in the H-W equilibrium,we were able to analyze symptoms versus allelic frequency of each SNP using a case-control design.3.The association between SNPs and clinical symptoms of non-small-cell-lung cancerBecause genotype frequency distributions of 2 SNPs were in the H-W equilibrium,we were able to analyze clinical symptoms versus SNPs using a case-control design.The results were shown as follows:3.1 The allele and genotype of MDM2SNP1 was associated with cough (X~2=6.613,df=1,P=0.012;X~2=0.6157,P=0.0045).The frequency of allele A was higher in the patients with cough than those without the symptom..3.2 The allele of MDM2SNP1 was associated with bloody sputum(X~2 =12.438, P=0.0004).The frequency of allele A was lower in the patients with bloody sputum than those without the symptom..3.3 The allele of MDM2SNP2 was associated with dyspemia(X~2=5.45, df=1,P=0.019).The frequency of allele A was lower in the patients with dyspernia than those without the symptom.Taken together,the present study demonstrates that MDM2SNP1 may be associated with the susceptibility of non-small-cell lung cancer.MDM2SNP1 and MDM2SNP2,were associated with some positive symptoms of non-small-cell lung cancer.These findings are very important for elucidating the molecular genetic mechanisms of non-small-cell lung cancer,and also for genetic diagnosis,developing new drugs and prediction of non-small-cell lung cancer.