广西扶绥县肝癌家系人群TSPAN8基因单核苷酸多态性与肝癌遗传易感性研究

发布时间：2018-08-08 21:19

【摘要】：目的:探讨TSPAN8基因rs1051334、rs2270587位点单核苷酸多态性与广西扶绥县肝癌高发区肝癌家系遗传易感性的关系。方法:采用病例-对照研究方法,收集广西扶绥县肝癌高发地区20个肝癌高发家系(共79例,其中肝癌患者20例及直系亲属59例)及10个正常对照家系(共40例)作为研究对象,运用飞行时间质谱分析技术(MALDI-TOF)检测TSPAN8基因rs1051334、rs2270587位点基因型。运用SPSS 17.0软件对数据进行统计分析。所有统计学分析结果采用双侧概率检验,以P0.05为差异具有统计学意义。根据Hardy-Weinberg遗传平衡定律检测各组人群基因型吻合度。使用χ~2检验计算各组人群等位基因型分布差异。并应用非条件Logistic回归模型分析该基因候选位点基因型多态性与肝癌家系遗传易感性的关系。结果:1.(1)肝癌高发家系组人群TSPAN8基因rs1051334位点携带TT、TG、GG3种基因型,其分布频率分别是55.7%、34.2%、10.1%;对照家系组人群TSPAN8基因rs1051334位点携带TT、TG、GG3种基因型,其分布频率分别是62.2%、35.1%、2.7%。两组各基因型实际值与期望值吻合度好(P0.05)。(2)肝癌高发家系组人群TSPAN8基因rs2270587位点携带CC、CT、TT3种基因型,其分布频率分别是67.1%、31.6%、1.3%;对照家系组人群TSPAN8基因rs2270587位点携带CC、CT、TT3种基因型,其频率分别是50.0%、45.0%、5.0%。两组各基因型实际值与期望值吻合度好(P0.05)。2.(1)肝癌高发家系患者组、肝癌高发家系非患者组及正常对照家系组人群TSPAN8基因rs1051334位点T等位基因频率分别为72.5%、72.9%和79.7%,G等位基因频率分别为27.5%、27.1%、20.3%。肝癌高发家系患者组与非患者组等位基因频率分布无显著差异(χ~2=0.002,P=0.963),肝癌高发家系患者组与正常对照家系组等位基因频率分布无显著差异(χ~2=0.771,P=0.380)。在肝癌高发家系非患者组人群中,携带GT基因型的个体发生HCC的风险是携带TT基因型个体的1.15倍(95%CI为0.32~4.13);携带GG基因型的个体发生HCC的风险是携带TT基因型个体的0.62倍(95%CI为0.08~4.87)。在正常对照家系组人群中,携带GT基因型的个体发生HCC的风险是携带TT基因型个体的2.82倍(95%CI为0.52~15.27),携带GG基因型的个体发生HCC的风险是携带TT基因型个体的3.61倍(95%CI为0.21~63.44),但差异均无统计学意义(P0.05)。(2)肝癌高发家系患者组、非患者组及正常对照家系组人群TSPAN8基因rs2270587位点C等位基因频率分别为90.0%、80.5%和72.5%,T等位基因频率分别为10.0%、19.5%、27.5%。肝癌高发家系患者组与非患者组等位基因频率分布无显著差异(χ~2=1.899,P=0.168),肝癌高发家系患者组与正常对照家系组等位基因频率分布有显著差异(χ~2=4.812,P=0.028),正常对照家系组人群携带T等位基因型的个体发生HCC的风险是携带C等位基因型个体的0.29倍(95%CI为0.09~0.92)。在肝癌家系非患者组人群中,携带CT基因型的个体发生HCC的风险是携带CC基因型个体的0.42倍(95%CI为0.11~1.66),但未见显著差异(P0.05),携带TT基因型的个体发生肝癌的风险无法计算出来。在正常对照家系组人群中,携带CT基因型的个体发生HCC的风险是携带CC基因型个体的0.34倍(95%CI为0.07~1.59),但未见显著差异(P0.05),携带TT基因型的个体发生肝癌的风险无法计算。结论:1.在广西扶绥县人群中,TSPAN8基因rs1051334位点、rs2270587位点各基因型分布符合Hardy-Weinberg遗传平衡定律;2.TSPAN8基因rs1051334位点单核苷酸多态性与广西扶绥县人群肝癌家系的遗传易感性无明显相关性;3.TSPAN8基因rs2270587位点单核苷酸多态性与广西扶绥县人群肝癌家系的遗传易感性有相关性,rs2270587位点T等位基因为广西扶绥县人群HCC发生的保护因素。
[Abstract]:Objective: To investigate the relationship between the single nucleotide polymorphism of TSPAN8 gene rs1051334 and rs2270587 loci and the genetic susceptibility to HCC families in the high incidence area of liver cancer in Fusui County, Guangxi. Methods: a case control study was used to collect 20 HCC families (79 cases, including 20 cases of liver cancer and 59 cases of direct relatives) in the high incidence area of liver cancer in Fusui County, Guangxi. 10 normal controls (a total of 40 cases) were used as the research object, using time of flight mass spectrometry (MALDI-TOF) to detect TSPAN8 gene rs1051334 and rs2270587 genotype. The data were statistically analyzed using SPSS 17 software. All statistical analysis results were tested by bilateral probability, and P0.05 was statistically significant. According to H Ardy-Weinberg's law of genetic balance was used to detect the genotypic degree of genotype in each group. The difference of genotype distribution in each group was calculated using the chi square ~2 test. The relationship between the genotype polymorphism of the candidate loci and the genetic susceptibility of HCC families was analyzed by the non conditional Logistic regression model. Results: 1. (1) TSPAN8 of the HCC family group The gene rs1051334 loci carried TT, TG, and GG3 genotypes, and their distribution frequencies were 55.7%, 34.2%, 10.1% respectively. The rs1051334 loci of TSPAN8 gene in the control family group were carried by TT, TG, and GG3 genotypes, and the distribution frequencies were 62.2%, 35.1%, and 2.7%. two respectively. (2) the hepatocellular carcinoma HCC group group TS The rs2270587 loci of the PAN8 gene carry CC, CT, and TT3 genotypes, the frequencies of which are 67.1%, 31.6%, 1.3% respectively. The TSPAN8 gene rs2270587 loci of the control family group carry CC, CT, TT3 genotypes, and the frequencies of the genotype are 50%, 45%, and 5.0%. two, respectively. The frequency of T allele of TSPAN8 gene rs1051334 loci of HCC non patient group and normal control family group was 72.5%, 72.9% and 79.7% respectively, and the frequency of G allele was 27.5% and 27.1% respectively. There was no significant difference in the allele frequency distribution of 20.3%. HCC group and non patient group (x ~2=0.002, P=0.963), HCC high hair family. There was no significant difference in the allele frequency distribution between the group and the normal control group (x ~2=0.771, P=0.380). In the non patient group of the HCC family, the risk of HCC carrying GT genotype was 1.15 times that of the TT genotype (95%CI 0.32~4.13), and the risk of HCC carrying GG genotype was TT based. 0.62 times (95%CI 0.08~4.87) of the type individual. In the normal control group, the risk of HCC in individuals carrying GT genotype was 2.82 times as high as that of the TT genotype (95%CI 0.52~15.27), and the risk of HCC carrying GG genotype was 3.61 times that of the TT genotype (95%CI 0.21~63.44), but the difference was not statistically significant. (2) (2) the frequency of the C allele of the rs2270587 locus of the TSPAN8 gene was 90%, 80.5% and 72.5% in the non patient group and the normal control group, respectively, and the frequency of the T allele was 10% and 19.5%, respectively, and there was no significant difference in the allele frequency distribution between the HCC patients and the non patients group (x ~2=1). .899, P=0.168), the allele frequency distribution of HCC patients was significantly different from that of normal control family group (x ~2=4.812, P=0.028). The risk of HCC in individuals carrying T allele in normal control family group was 0.29 times as much as C allelic individuals (95%CI 0.09~0.92). The risk of HCC with the CT genotype was 0.42 times that of the CC genotype (95%CI 0.11~1.66), but there was no significant difference (P0.05). The risk of cancer carrying the TT genotype could not be calculated. In the normal control family group, the risk of carrying HCC in CT based individuals was carried by the CC genotype individual. 0.34 times (95%CI 0.07~1.59), but no significant difference (P0.05), the risk of hepatocellular carcinoma with TT genotype could not be calculated. Conclusion: 1. in the population of the TSPAN8 gene in Fusui County, Guangxi, the genotype distribution of the rs2270587 loci conforms to the Hardy-Weinberg genetic balance law, and the 2.TSPAN8 gene rs1051334 loci single nucleotide. There is no significant correlation between polymorphism and genetic susceptibility to liver cancer families in Fusui County, Guangxi. The single nucleotide polymorphism of 3.TSPAN8 gene rs2270587 loci is related to the genetic susceptibility of liver cancer families in Fusui County of Guangxi, and the rs2270587 locus T allele is the protection factor of HCC in Fusui County of Guangxi.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.7

【参考文献】