| The Human Genome Project (HGP) has been completed. These scientific achievements facilitate the human being to understand themselves well and unravel the mystery of life science. The major purpose of the HGP is to solve the molecular genetic problems regarding human serious diseases. Most human serious diseases, such as tumor, cardio-brain-vascular disease and neuro-psychiatric disorders, are all associated with genetic factors. The sequence of Human Genome Project (HGP) includes all the informations of the course of life of human beings. It will promote the advance of biology and medicine greatly in this century as a special control of groundback of life. Human Genome Project has been planning to digest human gene DNA sequence into as many as 15O-2O0bp fragments, and reconstruct them into the germ clone and to be sure that the accuracy is over 99.9%. Single nucleotide polymorphism (SNP) provides the basis of the research of variations of human gene sequence. The sequence of Human Genome Project is a draft coming from a few people and it can reflect the stable aspects of human genome, but it can't reflect the varied aspects of human genome. SNP is a very efficient gene analyse tool and it can help us explore the relationships between some special sites and many diseases. The occurrence rate of SNP is ISNP/kb. Mapping and constructing the SNP map can provide a complete description of all the genes. It is beneficial to elucidate the difference of phenotype and susceptibility to disease of individual person. On the basis of high density and high polymorphisms SNP map, genome scanning and association study are used to screen for more relative genes of complex diseases. It makes a great progress in mapping the susceptibility genes of polygenic disease. These studies will accelerate the pace of the description and translation of the sequence of Human Genome Project greatly. 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. P53 gene has been reported as one of the most associated genes with malignant tumor. Epidemiological data demonstrate that lung cancer is not a simple Mendelian disease but it looks like a complex disease with a polygenic mechanism. The present study has been focused on identifying the candidate SNPs on p53 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. 4 SNPs were chosen by accessing the databases at http://www.ncbi.ribn.nih.eov/, 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 4 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 cancer 2.1 Association between genotype of SNPs and non-small-cell lung cancer Because genotype frequency distributions of 4 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 C/C genotype of TP53SNP1 is higher significantly in NSCLC than that of control. ( x 2=9.33 , P =0.00230), The frequency of G/G genotype of mdm2SNP3 is higher significantly in NSCLC than that of control ( x 2=29.67 , P <0.001) .These results suggeste that TP53SNP1 and mdm2SNP3 associated with the susceptibility of non-small-cell lung cancer. 2.2 Association between allele of SNPs and non-small-cell lung cancer Because allele frequency distributions of 4 SNPs were in the H-W equilibrium, we were able to analyze symptoms versus allelic frequency of each SNP using a case-control design. We found that the frequency of C allele of TP53SNP1 is higher significantly in NSCLC than that of control. (x 2=5.65 , P =0.017), The result suggestes that TP53SNP1 associated with the susceptibility of non-small-cell lung cancer.
|
PDF Full Text Request