Pin1基因多态性与喉鳞状细胞癌的相关性研究

发布时间：2018-04-28 19:06

本文选题：喉肿瘤 + 单核苷酸多态性　；参考：《天津医科大学》2011年硕士论文

【摘要】：目的检测]Pinl (peptidyl-prolyl cis/trans isomerase 1)启动子区域和内含子区域的单核苷酸多态性(single nucleotide polymorphism, SNP)位点rs2233678、rs2233679和rs2287838在喉鳞状细胞癌(laryngeal squamous cell carcinoma, LSCC)患者及其对照组人群外周血中的基因型频率和等位基因型频率。比较上述多态性位点基因型频率和等位基因型频率在两组中的差异,分析其分布频率与不同临床参数(如颈部淋巴结转移及临床分期)的关系。旨在寻求具有重要临床意义的诊断指标和治疗靶点,明确它们和LSCC发生发展的关系,为LSCC早期的基因型诊断以及靶向治疗提供科学依据。方法采用聚合酶链式反应-限制性内切酶片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP)方法检测LSCC患者以及非癌症对照组人群外周血中Pin1基因相关的SNP位点,即rs2233678、rs2233679和rs2287838(其中rs2233678和rs2233679两个位点位于Pin1基因的启动子区域,rs2287838位点位于Pin1基因的内含子区域)的单核苷酸多态性在两组中的差异；并比较突变位点的基因型频率以及等位基因型频率与患者颈部淋巴结转移、临床分期间的关系。应用SPSS16.0统计学软件对实验数据进行分析。应用拟合优度χ2检验对对照组基因型频率分布行Hardy-Weinberg平衡分析；病例组与对照组基因型和等位基因型频率分布比较用χ2检验,以比值比(odds ratio, OR)及其95%可信区间(confidence interval, CI)来表示基因型之间的相对风险度。P0.05作为差异有统计学意义的标准。结果 1.对照组人群三个位点分别经过Hardy-Weinberg遗传平衡检验,P0.05,符合Hardy-Weinberg遗传平衡定律,具有群体代表性。 2.rs2233678多态性位点的基因型频率分布在病例组和对照组中差别有明显统计学意义(P=0.004)。对其临床参数分组分别进行统计学分析发现其基因型频率分布在淋巴结转移、TNM临床分期分组中差别无统计学意义。进一步对其基因型进行相对风险度分析,GG基因型发生喉鳞癌的危险性是GC+CC基因型的3.821倍(P=0.001, OR=3.821,95%CI=1.632-8.948); G等位基因突变的喉鳞癌发病风险性是C等位基因型的3.858倍(P=0.001, OR=3.858, 95%CI=1.716-8.673). 3.rs2233679多态性位点的基因型频率分布在病例组和对照组中差别无明显统计学意义(P=0.207)。 4.rs2287838多态性位点的基因型频率分布在病例组和对照组中差别有明显统计学意义(P=0.000)。对其临床参数分组分别进行统计学分析rs2287838多态性位点的基因型频率分布在淋巴结转移、TNM临床分期分组中差别无统计学意义。进一步对其基因型进行相对风险度分析,以rs2287838 TT基因型为参照,CT基因型发生喉鳞癌的危险性是TT基因型的0.141倍(P=0.000, OR=0.141, 95%CI=0.060-0.330); CC基因型是TT基因型发生喉鳞癌风险性的0.323倍(P=0.012, OR=0.323,95%CI=0.131-0.796)。T等位基因突变的喉鳞癌易感性是C等位基因突变的1.470倍(p=0.059, OR=1.470,95%CI=0.985-2.193),但是差别处于临界值,未达到统计学意义。结论 1.rs2233678多态性位点与喉鳞状细胞癌易感性有关。但是rs2233678位点基因型突变不参与喉鳞癌的淋巴结转移以及恶性进展。G等位基因突变与喉癌的发病有关,促进喉鳞癌的发生。 2.rs2233679多态性位点与喉鳞状细胞癌易感性无相关性。 3.rs2287838多态性位点与喉鳞状细胞癌易感性有关。TT基因型与喉鳞癌的易感性有关,促进喉鳞癌的发生。但是rs2287838位点基因型突变不参与喉鳞癌的淋巴结转移以及恶性进展。
[Abstract]:objective
Detection of genotype frequency in peripheral blood of]Pinl (peptidyl-prolyl cis/trans isomerase 1) single nucleotide polymorphisms (single nucleotide polymorphism, SNP) loci in the promoter region and intron region of the peripheral blood of the laryngeal squamous cell carcinoma and the control group. The differences in genotype frequency and allele frequency in the two groups were compared. The relationship between the frequency of the polymorphic loci and the allele frequency in the two groups was analyzed. The relationship between the frequency of the distribution and the different clinical parameters, such as the cervical lymph node metastasis and the clinical stage, was analyzed. The purpose was to find the diagnostic indicators and therapeutic targets with important clinical significance, and to clarify their and LSCC hair. The relationship between growth and development provides a scientific basis for early diagnosis and targeted therapy of LSCC.
Method
The polymerase chain reaction restriction endonuclease fragment length polymorphism (polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP) was used to detect the Pin1 gene related SNP loci in peripheral blood of patients with LSCC and non cancer control groups. 9 the two loci are located in the promoter region of the Pin1 gene and the difference in the single nucleotide polymorphism of the rs2287838 loci in the intron of the Pin1 gene. The relationship between the genotype frequency of the mutation site and the allele frequency of the allele with the cervical lymph node metastasis and the clinical staging is applied. The SPSS16.0 statistics software is used. The analysis of experimental data was carried out. Hardy-Weinberg balance analysis was applied to the genotype frequency distribution of the control group by using the goodness of fit chi 2 test. The genotype and allele frequency distribution of the case group and the control group were compared with the x 2 test, and the ratio Ratio (odds ratio, OR) and the 95% credible region (confidence interval, CI) were used to express the genotype between the two groups. The relative risk.P0.05 was statistically significant.
Result
1. the three locus of the control group were tested by Hardy-Weinberg genetic equilibrium, P0.05, which was in line with the Hardy-Weinberg genetic balance law.
The genotype frequency distribution of 2.rs2233678 polymorphic loci was significantly different in the case group and the control group (P=0.004). The statistical analysis of its clinical parameters found that the frequency distribution of the genotype was in the lymph node metastasis, and there was no statistical significance in the TNM clinical staging group. For the risk analysis, the risk of GG genotypes in laryngeal squamous cell carcinoma is 3.821 times the GC+CC genotype (P=0.001, OR=3.821,95%CI=1.632-8.948), and the risk of laryngeal squamous cell carcinoma with G allele mutation is 3.858 times as much as C allele (P=0.001, OR=3.858, 95%CI=1.716-8.673).
There was no significant difference in genotype frequency distribution between 3.rs2233679 and polymorphic loci in case group and control group (P=0.207).
The genotype frequency distribution of 4.rs2287838 polymorphic loci was significant (P=0.000) in the case group and the control group (P=0.000). The genotype frequency distribution of the rs2287838 polymorphic loci was statistically analyzed in the lymph node metastasis, and the difference was not statistically significant in the TNM clinical subdivision. The genotype was analyzed with the relative risk degree, with the rs2287838 TT genotype as the reference. The risk of CT genotype of laryngeal squamous cell carcinoma was 0.141 times the TT genotype (P=0.000, OR=0.141, 95%CI=0.060-0.330), and CC genotypes were 0.323 times of the risk of laryngeal squamous cell carcinoma in the TT genotype (P= 0.012, OR=0.323,95%CI=0.131-0.796) gene mutation of the allele. The susceptibility of squamous cell carcinoma was 1.470 times that of the C allele (p=0.059, OR=1.470,95%CI=0.985-2.193), but the difference was at a critical value, and did not reach statistical significance.
conclusion
1.rs2233678 polymorphic loci are associated with susceptibility to laryngeal squamous cell carcinoma. However, the mutation of the rs2233678 loci is not involved in the lymph node metastasis of laryngeal squamous cell carcinoma and the mutation of the malignant progression.G allele is associated with the incidence of larynx cancer, which promotes the occurrence of laryngeal squamous cell carcinoma.
There was no correlation between 2.rs2233679 polymorphisms and susceptibility to laryngeal squamous cell carcinoma.
3.rs2287838 polymorphic loci are associated with susceptibility to laryngeal squamous cell carcinoma and the.TT genotype is associated with susceptibility to laryngeal squamous cell carcinoma, promoting the occurrence of laryngeal squamous cell carcinoma, but the genotype mutation at the rs2287838 site does not participate in the lymph node metastasis and malignant progression of laryngeal squamous cell carcinoma.

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R739.65

【参考文献】