【作者】 陈玲；

【导师】 李锋；

【作者基本信息】 石河子大学 ， 病理学与病理生理学， 2007， 硕士

【摘要】 目的(1)探讨HPV感染与新疆哈萨克族食管鳞癌(ESCC)病因学的相关性。(2)探讨TAP1基因多态性及HPV感染与新疆哈萨克族ESCC的相关性。方法(1)采用聚合酶链反应(PCR)检测了316例新疆哈族食管鳞癌和66例“正常”食管粘膜组织标本中HPVL1,16,18,31,45的感染情况,PCR产物双向测序,测序结果应用BLAST在线分析。(2)运用PCR-RFLP方法检测150例新疆哈族食管癌患者和283例同一地区无肿瘤病史的正常对照者的TAP1 Codon333和Codon637基因型分布。(3)统计处理采用χ2检验,并检验基因型的分布是否符合Hardy-Weinberg平衡方程。结果(1) 316例新疆哈族ESCC中HPV的总感染率、HPV-16/18/31/45E7的感染率、多重感染率分别为64.6%、41.4%、25.3%、14.2%、7.3%和17.7%,66例“正常”食管粘膜中的感染率分别为18.2%、15.2%、9.1%、4.5%、1.5%和4.5%,除HPV45外,二者之间差异均有统计学意义(P<0.05),HPV L1、HPV-16、-18、多重感染率的OR值分别为8.196、3.941、3.390、和4.523。(2)150例新疆哈族食管鳞癌中TAP1 Codon637位点三种基因型A/A,A/G,G/G所占比例分别是48.6%,46.7%,4.7%,哈族正常对照组中分别是61.1%,36.1%,2.8%,三种基因型频率相比差异有统计学意义(P <0.05),携带G等位基因的基因型提高机体患癌风险1.659倍。(3)150例新疆哈族食管鳞癌中TAP1 Codon333位点三种基因型A/A,A/G,G/G所占比例分别是54.7%, 41.3%,4.0%,哈族正常对照组中分别是47.3%,46.0%,6.7%,二者相比差异无统计学意义(P>0.05)。(4) TAP1Codon637位点三种基因型频率在HPV阳性组和HPV阴性组间比较,差异有统计学意义, P <0.05,TAP1Codon333三种基因型频率在HPV阳性组和HPV阴性组之间差异无统计学意义。结论(1) HPV感染与新疆哈萨克族ESCC的病因学有相关性,可能是其发病的危险因素之一,HPV-16和18型是新疆哈族ESCC的主要高危亚型。(2) TAP1Codon 637位点的基因多态性可能是新疆哈族食管癌遗传易感的因素之一。TAP1Codon333位点的基因多态性与新疆哈族食管癌的遗传易感性可能无关。(3)TAP1Codon637位点的基因多态性和哈族食管癌中HPV感染可能有相关性。TAP1Codon333位点的基因多态性和哈族食管癌中HPV感染可能无相关性。更多还原

【Abstract】 Objective: (1) Evaluate the prevalence of HPV infection in Kazakh esophageal squamous cell carcinoma(ESCC)of Xinjiang.(2)To investigate correlations of the polymorphisms at TAP1 genes (Transporter associated with antigen processing), with the risk of Kazakh ESCC in Xinjiang. Analyze the combined effect of TAP1 and HPV infection on ESCC in Kazakh in Xinjiang.Methods: (1)Polymerase chain reaction(PCR) was employed to screen HPV infection statuses of all samples based on five pairs of primers(general primers GP5+/6+ for HPV L1, type-specific primer for HPV-16,18,31,45.(2)TAP1 Codon333 and Codon637 genotypes were detected by a PCR-based RFLP assay in 150 cases with esophageal carcinoma and 283 cases cancer-free controls in the same area. (3)Theχ2 test was adopted to check the difference in genotype distribution between cases and controls, and the accordance with Hardy-Weinberg equilibrium in the group.Results:(1) The general infection rates, infection rates of HPV-16,18,31,45E7 and multi-infection statuses were analyzed between ESCC and“normal”esophageal carcinoma(NE), the results were as follows: the general infection rates, infection rates of HPV-16,18,31 type and multi-infection statuses , were significantly higher in ESCC than those in NE﹙P<0.05﹚, the infection rates were 64.6%,41.1%,25.3%,14.2%, 7.3% and 4.5%,18.2%, 15.2%, 9.1%, 4.5%,1.5%and 4.5%,respectively., The OR values of HPV-16, 18 and multi-infection statuses were 8.196,3.941, 3.390 and 4.523 , respectively;. (2) The frequencies of AA, AG and GG in TAP1 Codon637 were 48.6%,46.7% and 4.7% in Kazakh’s individuals with EC, and 22.8%,52.6%and 24.6% in Kazakh’s controls, respectively, a significant difference between frequencies of A/A ,A/G and G/Gwas found(P <0.05). The genotype with G allele improved the odds ratio for individuals with EC 1.659.(3)The frequencies of AA, AG and GG in TAP1 Codon333 were 54.7%,41.3%,and 4.0% in Kazakh’s individuals with EC, respectively. They were not significantly different from that in Kazakh’s controls (47.3%,46.0% and 6.7%). (4).The genotype frequency of TAP1Codon637 polymorphisms, there is significant difference between HPV positive cases and HPV negative cases, P <0.05. however, for the three genotpyes of TAP1Codon333, there is no significant difference between HPV positive cases and HPV negative cases. Conclusion: (1). HPV DNA infection had relationship in Kazakh ESCC of Xinjiang. HPV-16, 18 were the most common types, HPV infection may be one of risk factor in Kazakh ESCC. (2). There may be one of genetic susceptibility factors that TAP1 Codon637 polymorphism of EC in Kazakh in Xinjiang. There maybe no relationship between the TAP1 Codon333 polymorphism and risk of Kazakh esophageal carcinoma in Xinjiang. (3). TAP1 Codon637 polymorphism and HPV infection may be associated with Kazakh esophageal cancer in Xinjiang.更多还原