| Background and ObjectivesNasopharyngeal carcinoma is the high incidence of cancer in China and is one of the high incidence of tumors in Guangxi. Nasopharyngeal carcinoma were caused by the Epstein-Barr virus infection, chemical carcinogens and genetic susceptibility factors.However, the different groups of people in the same area and the same exposure conditions are not suffered from cancer, which there are differences in individuals in genetic susceptibility.Single nucleotide polymorphism (SNP) is the most common form of human genetic variation, accounting for more than 90% of all known polymorphisms,which is research focus of the tumor in recent years.The main purpose of this project is study the relations between tumor suppressor gene single nucleotide polymorphisms and nasopharyngeal cancer occurrence and developments,to provide relevant theoretical basis for the diagnosis and treatment of nasopharyngeal carcinoma. Some tumor suppressor genes were selected, including p53, p16 and Rb. Related tumor-suppressor genes SNP site were studied in Nasopharyngeal carcinoma patients and Control group.The role of genetic susceptibility were expected to clarify in nasopharyngeal carcinoma occurrence and development,which can also be used for the screening the high risk group and provide a theoretical basis for early intervention of nasopharyngeal carcinoma.In this study,6 SNP sites of p53, p16 and Rb were studied in Nasopharyngeal carcinoma patients and Control group. The role and the mutual relationship were expected between the related tumor suppressor gene p53,p16 and Rb and Nasopharyngeal carcinoma occurrence and development in Guangxi. To lay the foundation for the further development of gene chips for high-throughput detection,to provide new ideas diagnosis and treatment of nasopharyngeal carcinoma,to further reduce the incidence and mortality of nasopharyngeal carcinoma and in order to better for the patients.Materials and Methods1.Sample and data collection A total of 200 NPC blood samples(100 cases of men and 100 cases of women) were selected from June 2010 to April 2011 in Affiliated Tumor Hospital of Guangxi Medical University, Department of Radiation Oncology,and clinical data were collected. A total of 200 Control group blood samples were selected from healthy voluntary blood donors(100 cases of men and 100 cases of women).The two group population's blood samples are derived from Nanning,Guangxi. The define standard of Nasopharyngeal carcinoma group and control group:Nasopharyngeal carcinoma groups:are diagnosed by the Clinical and Pathological;each of the patients were not received chemotherapy, radiation therapy or biological treatment of intervention treatment measures before hospitalization. Control group:from the healthy volunteer donors.2. MethadsGenomic DNA were extracted from blood leukocytes of all participants,which be placed in a-20℃refrigerator after quantitative analysis. To observe the gene polymorphism and genetic mutation frequency distribution in the two groups, the SNP site were analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing methods.ResultsThe experimental research focus on the relationship between the common tumor-suppressor gene polymorphism and the genetic susceptibility of nasopharyngeal carcinoma.The results as follows:1. p53,p16 and Rb gene polymorphism and the genetic susceptibility of nasopharyngeal carcinoma1.1 p53 gene1.1.1 Among the NPC group and Control group, the genetic mutation rate of SNP locus rs117562731 of p53 were 20.0%(40/200) and 7.0%(14/200) respectively. The allele and genotype frequency had significant difference between the patients with the normal population(x2=2.933, p=0.402).1.1.2 Among the NPC group and Control group, the genetic mutation rate of SNP locus rs114831472 of p53 gene were 12.5%(25/200) and 7.5%(15/200) respectively. The allele and genotype frequency had no significant difference between the patients with the normal population (χ2=2.933,P=0.402).1.2 p16 gene1.2.1 The Nasopharyngeal carcinoma group and Control group, the genetic mutation rate of SNP site rs80235406 of p16 gene were 26.5% (53/200) and 9.0%(18/200) respectively. The allele and genotype frequency had significant difference between the patients with the normal population(χ2=20.977, P=0.000).1.2.2 The Nasopharyngeal carcinoma group and Control group, the genetic mutation rate of SNP site rs 121434309 of p16 gene were 22.5%(45/200) and 8.5%(17/200) respectively. The allele and genotype frequency had significant difference between the patients with the normal population(χ2=14.965, P=0.000).1.3 Rb gene1.3.1 The Nasopharyngeal carcinoma group and Control group, the genetic mutation rate of SNP site rs 117538467 of Rb gene were 34.5%(69/200) and 11.5%(23/200) respectively. The allele and genotype frequency had significant difference between the patients with the normal population(x2=29.870, P=0.000).1.3.2 The Nasopharyngeal carcinoma group and Control group, the genetic mutation rate of SNP site rs 117538467 of Rb gene were 28.0%(56/200) and 12.5%(25/200)respectively. The allele and genotype frequency had significant difference between the patients with the normal population(χ2=14.877, P=0.000).2. p53,p16 and Rb gene and NPC clinical phenotypesWe analyzed the distribution of p53,p16 and Rb gene genotypes among difference clinical characteristics and assessed the relationship between these gene polymorphism and clinical and characteristics in 200 NPC patients.2.1 We found a significant associated between the p53 gene SNP locus rs114831472 GG genotype frequency and primary tumor T stages. (GG versus AA,7.9% VS 1.2%,p=0.017). The significant associated between the p53 gene SNP locus rs117562731 CT genotype frequency and distant metastasis (M stage). (CT versus CC, 44.4% VS 15.7%,p=0.030).2.2 The p16 gene SNP locus rs80235406 TT polymorphism had significant difference with Lymph node metastasis (N stage)(TT versus CC,1.6% VS 9.4%,p=0.011).The p16 gene SNP locus rs80235406 TT and rs121434309 GG polymorphism had significant difference with distant metastasis (M stage). (TT versus CC,3.1% VS 33.3%,p=0.000; GG versus AA,22.2% VS2.1%,p=0.001).2.3 The Rb gene SNP locus rs117538467 GG and rs117209587 GG polymorphism had significant difference with distant metastasis (M stage). (GG versus CC,4.2% VS 33.3%,p=0.023; GG versus AA,22.2% VS3.1%,p=0.002).Conclusions1. Among the NPC group and Control group, the genetic mutation and distribution of SNP locus rs114831472 of p53 gene had no significant difference between the patients with the normal population. The result indicates that the SNP locus rs114831472 of p53 gene polymorphism is not significantly associated with Nasopharyngeal carcinoma. 2. Among the NPC group and Control group, the genetic mutation and distribution of SNP locus rs117562731 of p53 gene had significant difference between the patients with the normal population. The result indicates that the SNP locus rs117562731 of p53 gene polymorphism is significantly associated with Nasopharyngeal carcinoma.3. Among the NPC group and Control group, the genetic mutation and distribution of SNP locus rs80235406 and rs121434309 of p16 gene had significant difference between the patients and the normal population. The result indicates that the SNP locus rs80235406 and rs 121434309 of pi6 gene polymorphism is significantly associated with Nasopharyngeal carcinoma.4. Among the NPC group and Control group, the genetic mutation and distribution of SNP locus rs117538467 and rs117538467 of Rb gene had significant difference between the patients and the normal population. The result indicates that the SNP locus rs117538467 and rs117538467 of Rb gene polymorphism is significantly associated with Nasopharyngeal carcinoma.5. The p53, p16 and Rb genetic polymorphism had significant difference with clinical phenotype and progression of nasopharyngeal carcinoma.
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