Study On Correlation Between The Polymorphism Of Human Mdm2 Gene And Non-Small Cell Lung Cancer

The completion of Human Genome Project (HGP) will promotethe advance of biology and medicine greatly in next century.Medicine scientists will apply these research results to resolve allkinds of problems of human disease's diagnosis, therapy andprevention. In the 21 century, the fruit of gene medicine will befound in any medicine field.The sequence of Human Genome Project is a draft coming froma few people and it can reflect the stable aspects of human genome,but it can't reflect the varied aspects of human genome. Theinformation of human genome can be divided into two directions.The portrait is checking all the sequences of nucleotide acid. Thelandscape is checking the variation of sequence. SNP is the widestvariation of sequence. It distributes in the genome DNA, about 1 per1000 base pair(bp). It represents the biggest variation in differentindividuals. SNP can be divided into two kinds: Firstly, functionalmutation in the gene coding region, i.e. cSNP, they are moreimportant than the SNP locating in controlling sequence. This kindof SNP is called functional polymorphism. Secondly, much variationof single base pair locates in the non-coding region of genome DNA.Nowadays, SNP has been widely used in finding high risk group,identifying correlative disease gene, designing and testing medicineand basic biologic research, et al.The incidence and mortality of lung cancer has been increasinggradually recent years. Because the progress of small cell lungcancer obviously differs from other types of pathology, so lungcancer is divided into non-small cell lung cancer (NSCLC) and smallcell lung cancer (SCLC). NSCLC occupies about 75% of lung cancer,70% of NSCLC need radiation therapy. In fact, surgery is the firstselected treatment, but for many reasons, only 25% of lung cancerpatients can receive radical operation. So, quite a lot of patients needradiation therapy. The aim of radiation therapy is to improvetherapeutic enhancement ratio, i.e. make dose distribution focus ontarget, eliminate cancer cells, and avoid or decrease unnecessaryirradiation to normal tissues and organs. Improving radiationsensibility of tumor is an important method to enhance the curativeeffects. Many studies indicated many genes had correlation withtumor radiation sensibility, for example, oncogene, anti-oncogeneand DNA repair gene.On the basis of these studies, our study selected mdm2 gene onthe chromosome 12 as the susceptible gene and radiation sensibititygene. There were reports about the relationship between geneexpress and lung cancer. There wasn't any report about therelationship between mdm2 gene and tumor radiation sensibitity. Themdm2 gene is conservative gene in evolution. The mdm2 mRNA iswidely expressed in human and mouse's tissues, for example, lung,liver, muscle, thymus gland, et al. This reflects that it playsimportant role in basic cellular physiological process. In the normalcell, wild-type p53 and mdm2 gene act on each other and form afeed-back cycle. The level of Mdm2 protein is dominated by thelevel of wild type p53. If p53 gene is activated, it can induceenhancement of mdm2 gene transcription, so the level of Mdm2enhances, Mdm2 protein will combine with p53 to form a kind ofcomplex. That restrains the transcription of wild type p53, so that thetranscription of mdm2 gene will decrease. Many studies indicatedthat the expression of mdm2 in lung cancer is a frequentphenomenon.NSCLC patients and comparison were our study objects. Usingcase-control method and correlative analysis between NSCLCmdm2 gene genotype and curative effect, we tried to find thecorrelation between mdm2 polymorphism and NSCLC susceptibilityand radiation sensibitity. At one time, we tried to find the correlationbetween mdm2 polymorphism and NSCLC clinical symptoms,pathology. Technique route was followed in such a way that frompositive region determined by genome scanning to gene map, andSNP-based RFLP map. SNP were genotyped using PCR-based RFLPanalysis. Genotyping data were put into the SPSS database. TheHardy-Weinberg (H-W) equilibrium was tested for genotypefrequency distributions of SNP using the goodness of fit test. Byanalysis of clinical subgroups, we tried to approve the existing ofheterogeneity, and found susceptible gene of NSCLC.88 NSCLC cases with existing tumor were from radiationdepartment, Jilin University Hospital 2. 102 comparison cases werefrom health medical examination center. Clinical data's evaluating:(1) All of NSCLC cases receive CT examination before and oneweek after radiation therapy. We measured the size of tumor andcomputed the percent of tumor decreasing. On the base of entitytumor evaluation criterion of WHO, the NSCLC cases were dividedinto effective group and ineffective group. (2) The data of Clinicalsymptom and pathology is based on case history. All the data wererecord in SPSS data-base. The following are the details of majorresults obtained in this study.1. The H-W equilibrium:The goodness of fit test showed that genotype frequencydistribution of mdm2 is not deviated from the H-W equilibrium, andthus this sample pool was suitable for the genetic analysis.2. Correlation between SNP and NSCLC2.1 The correlation between mdm2 polymorphism and susceptibility ofNSCLCBy case-control study, mdm2 polymorphism was analyzed. Afterstatistic analysis, we found there was statistic significance in two groupsdistribution difference. It indicated that mdm2 gene is susceptible gene ofNSCLC.2.2 The correlation between mdm2 polymorphism and radiationsensibitity of NSCLCWe analyzed radiation sensibitity versus allelic and genotypicfrequency of mdm2 genotype using a case-control design. Afterstatistic analysis, we found there was no statistic significance in thedistribution difference between effective group and ineffective group. Itindicated that there wasn't correlation between mdm2 polymorphism andradiation sensibitity of NSCLC.2.3 The correlation between mdm2 polymorphism and symptoms ofNSCLCWe analyzed clinical symptoms versus allelic and genotypicfrequency of mdm2 genotype using a case-control design. We foundthere was obvious correlation between mdm2 AA genotype and cough.But there wasn't correlation between AA genotype and other clinicalsymptoms. Other genotypes have no correlation with any clinicalsymptom.2.4 The correlation between mdm2 polymorphism and pathology ofNSCLCWe analyzed pathology types versus allelic and genotypicfrequency of mdm2 genotype using a case-control design. Afterstatistic analysis, we found there was no statistic significance in threepathology types distribution difference. It indicates that there wasn'tcorrelation between mdm2 polymorphism and pathology types ofNSCLC.In all, we found that mdm2 gene polymorphism was correlatedwith the susceptibility of NSCLC. It indicated that mdm2 gene GGgenotype was susceptible genotype of NSCLC. Geneticists believethat for complex polygenic disease study, we should consider many...