GSTM1、PSCA基因多态性与膀胱癌发病风险的关系
发布时间：2019-06-03 02:03
【摘要】：目的 研究中国汉族人群谷胱甘肽转硫酶M1基因(Glutathione-S-transferase M1, GSTM1)GSTM1-02位点和前列腺干细胞抗原基因(Prostate Stem Cell Antigen, PSCA) rs2294008位点的多态性与膀胱尿路上皮细胞癌(BUCC)发病风险、病理分期分级及肿瘤复发之间的关系。 方法 采用病例-对照研究的方法,收集中国汉族膀胱尿路上皮癌患者358例和正常体检者434例的血液标本,将患者病案中的相关临床资料和体检者体检时记录的相关资料统一输入Excel数据库,病例组膀胱癌的诊断、病理分期和分级均经病理组织学确定,并对所有患者完成随访。提取病例组和对照组的血液基因组DNA,分别采用聚合酶链反应(PCR)和等位基因特异PCP(Allele-specific PCR, AS-PCR)的方法检测GSTM1和PSCA的基因多态性,并通过测序方法验证PSCA基因的分型结果。 统计 应用SPSS20.0for Windows统计软件包。采用t检验和x2检验联合分析病例组与对照组在性别、年龄、吸烟状况上的差异；以拟合优度x2检验进行Hardy-Weinberg平衡检验,比较对照人群实际基因型频率与预期基因型频率吻合程度；采用x2检验分析GSTM1-02和rs2294008两位点遗传变异与膀胱癌发病之间的关联,并计算变异型等位基因的个数和膀胱癌发病风险的剂量效应关系；通过多因素非条件Logistic回归控制主要暴露因素对基因遗传变异效应的混杂作用；通过分层分析探讨不同亚人群中GSTM1和PSCA基因遗传变异与膀胱癌发病及复发关联度的不同；采用Fisher确切概率法分析以上两种基因多态性与膀胱癌病理分期、分级之间的关系。比值比(Odd Ratio, OR)和95%置信区间(Confidence Intervals, CI)表示关联强度。所有检验均为双侧检验,检验水平a=0.05,P0.05为差异有显著意义。 结果 1.GSTM1基因GSTM1-02多态位点与膀胱癌发病风险的关系 通过PCR法检测到GSTM1基因GSTM1-02位点有GSTM1缺失(Null)和GSTM1非缺失(Non-null)两种基因型。以Non-null基因型为参照,采用x2检验发现Null变异基因型频率在病例组和对照组的分布差异无显著性(P0.05,校正OR=1.19,95%CI=0.89-1.58)。分层分析显示,在不同年龄、性别、吸烟状况的亚组人群中,Null变异基因型的频率分布亦无显著差异(P0.05)。 2.PSCA基因rs2294008多态位点与膀胱癌发病风险的关系 通过x2检验发现C/T和T/T变异基因型在病例组和对照组中的频率分布存在明显差异(P0.05)。以C/C基因型为参照,多因素非条件Logistic回归分析显示,C/T和T/T变异基因型携带者与膀胱癌的风险性上升有显著性关联(校正OR=1.54,95%CI=1.15-2.06),而且风险等位基因T与膀胱癌发病之间具有显著的剂量-反应关系(Ptrend=0.001)。分层分析显示,携带C/T和T/T变异基因型的个体发生膀胱癌的风险性在年龄65岁(校正OR=1.80,95%CI=1.17-2.75)、男性(校正OR=1.57,95%CI=1.14-2.18)、吸烟(校正OR=1.79,95%CI=1.15-2.80)的亚组人群中增加更为显著(P0.05)。进一步的基因-环境的交互作用分析未发现PSCA基因与环境之间存在交互作用(P0.05)。 3.GSTM1-02和rs2294008多态位点与膀胱癌病理分期、分级的关系 采用Fisher确切概率法发现,GSTM1和PSCA的变异基因型在病例组膀胱癌病理各分期、分级中的分布均无明显差异(P0.05)。 4.GSTM1-02和rs2294008多态位点与膀胱癌复发的关系 经x2检验发现,GSTM1和PSCA的变异基因型在复发组和未复发组的分布均无明显差异(P0.05)。分层分析显示,在不同年龄、性别、吸烟状况的亚组人群中,各变异基因型的频率分布亦均无显著差异(P0.05)。 结论 1.GSTM1基因GSTM1-02位点碱基缺失与中国汉族人群膀胱癌遗传易感性无明显相关。 2. PSCA基因rs2294008位点遗传变异可显著增加中国汉族人群罹患膀胱癌的危险性,尤其是在年龄65岁、男性、吸烟亚组中更为显著。 3. GSTM1-02位点碱基缺失和rs2294008位点多态性与中国汉族人群膀胱癌病理分期、分级均无显著性相关。 4. GSTM1-02位点碱基缺失和rs2294008位点多态性与中国汉族人群膀胱癌复发均无显著性相关。
[Abstract]:Purpose To study the relationship between the polymorphism of the GSTM1-02 site and the prostate Stem Cell Antigen (PSCA) rs2294008 and the pathogenic wind of the bladder urothelial carcinoma (BUCC) in the Chinese Han population The correlation between the risk, the stage of pathological stage and the recurrence of the tumor Department. Methods A case-control study was used to collect the blood samples of 358 cases of urothelial carcinoma of the Chinese Han and 434 cases of normal physical examination, and input the relevant clinical data in the patient's medical record and the relevant data recorded in the physical examination of the physical examination person to the Exc. The diagnosis, pathological staging and grading of bladder cancer in the el database and case group were determined by the pathological histology and all the patients The gene polymorphism of GSTM1 and PSCA was detected by polymerase chain reaction (PCR) and allele-specific PCP (Allele-specific PCR, AS-PCR), and the PSCA gene was verified by sequencing. Sub-section Type results. The statistical application SPSS10.0 for Win The sex, age and smoking status of the combined analysis case group and the control group were tested by t-test and x2 test. The Hardy-Weinberg equilibrium test was carried out with the fit of the goodness of fit x2 test to compare the actual genotype frequency and expectation of the control population. The relationship between the genetic variation of GSTM1-02 and rs2294008 and the incidence of bladder cancer was analyzed by x2 test, and the number of allotypic alleles and the incidence of bladder cancer were calculated. The relationship between the dose-response of the risk and the confounding effect of the main exposure factors on the genetic variation of the gene by multi-factor non-conditional logistic regression; the genetic variation of GSTM1 and PSCA genes in different subpopulations and the incidence of bladder cancer were discussed by means of hierarchical analysis. The relationship between the two genes and the pathological score of bladder cancer was analyzed by Fisher's exact probability method. The ratio ratio (Odd Ratio, OR) and the 95% confidence interval (Confidence Interval, CI) indicates the associated strength. All tests are double-sided, with a test level a = 0.05, P0.0 5 is The difference was significant. Results 1. GSTM1-02 in GSTM1 gene The relationship between the state site and the risk of bladder cancer is detected by the PCR method, and the GSTM1-02 site has the GSTM1 deletion (null) and the GSTM1 non-deletion. (Non-null) two genotypes. The Non-null genotype was used as the reference, and the distribution of null variant genotype frequency in the case group and the control group was not significant (P0.05) using the x2 test (P0.05). 5% CI = 0.89-1.58). The stratified analysis revealed the frequency of null variant genotypes in the subgroup population of different age, sex, smoking conditions There was no significant difference in distribution (P0.05).2. The PSCA gene rs2294 The relationship between the polymorphism site and the risk of bladder cancer was detected by x2 test, and the C/ T and T/ T mutation genotypes were found in the case group and the control group. There was a significant difference in the frequency distribution in the middle (P0.05). The C/ C genotype as the reference, the multi-factor non-conditional logistic regression analysis showed that the risk of C/ T and T/ T variant genotypes was significantly associated with the risk of bladder cancer (corrected OR = 1.54,95% CI = 1.15-2.06), and there was a significant dose between the risk allele T and the incidence of bladder cancer. -Reaction relationship (Ptrs = 0.001). The risk of bladder cancer in individuals carrying C/ T and T/ T mutation genotypes at age 65 (corrected OR = 1.80,95% CI = 1.17-2.75), male (corrected OR = 1.57,95% CI = 1.14-2.18), smoking (corrected OR = 1.79,95% CI = 1.15-2.80) There was a more significant increase in the subgroup population (P0.05). The further gene-environment interaction analysis did not find the PSCA group Due to the interaction with the environment (P0.05).3. GSTM1-02 and rs229 The relationship between the polymorphism site of the 4008 and the pathological stage and the grade of the bladder cancer was found by Fisher's exact probability method, and the mutation genotype of GSTM1 and PSCA in the case group of bladder cancer There was no significant difference in the distribution of stage and grade (P0.05).4. GSTM1 The relationship between the polymorphic site of-02 and rs2294008 and the recurrence of bladder cancer was found by x2 test, and the mutation groups of GSTM1 and PSCA There was no significant difference in the distribution of the non-recurrent group and the non-recurrent group (P0.05). in that present invention, The frequency distribution of each variant genotype was not significantly different (P0.05). Conclusion 1. GSTM1 gene GST The deletion of the base of the M1-02 locus is not related to the genetic susceptibility of the bladder cancer in the Chinese Han population. The risk of a group of bladder cancer, especially in the age of 65, is more pronounced in the male and in the smoking subgroup.3. The base of the GSTM1-02 site is missing and rs2 There was no significant correlation between the polymorphism of the 24008 site and the pathological staging and grade of bladder cancer in the Han population of China.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.14
本文编号：2491585
[Abstract]:Purpose To study the relationship between the polymorphism of the GSTM1-02 site and the prostate Stem Cell Antigen (PSCA) rs2294008 and the pathogenic wind of the bladder urothelial carcinoma (BUCC) in the Chinese Han population The correlation between the risk, the stage of pathological stage and the recurrence of the tumor Department. Methods A case-control study was used to collect the blood samples of 358 cases of urothelial carcinoma of the Chinese Han and 434 cases of normal physical examination, and input the relevant clinical data in the patient's medical record and the relevant data recorded in the physical examination of the physical examination person to the Exc. The diagnosis, pathological staging and grading of bladder cancer in the el database and case group were determined by the pathological histology and all the patients The gene polymorphism of GSTM1 and PSCA was detected by polymerase chain reaction (PCR) and allele-specific PCP (Allele-specific PCR, AS-PCR), and the PSCA gene was verified by sequencing. Sub-section Type results. The statistical application SPSS10.0 for Win The sex, age and smoking status of the combined analysis case group and the control group were tested by t-test and x2 test. The Hardy-Weinberg equilibrium test was carried out with the fit of the goodness of fit x2 test to compare the actual genotype frequency and expectation of the control population. The relationship between the genetic variation of GSTM1-02 and rs2294008 and the incidence of bladder cancer was analyzed by x2 test, and the number of allotypic alleles and the incidence of bladder cancer were calculated. The relationship between the dose-response of the risk and the confounding effect of the main exposure factors on the genetic variation of the gene by multi-factor non-conditional logistic regression; the genetic variation of GSTM1 and PSCA genes in different subpopulations and the incidence of bladder cancer were discussed by means of hierarchical analysis. The relationship between the two genes and the pathological score of bladder cancer was analyzed by Fisher's exact probability method. The ratio ratio (Odd Ratio, OR) and the 95% confidence interval (Confidence Interval, CI) indicates the associated strength. All tests are double-sided, with a test level a = 0.05, P0.0 5 is The difference was significant. Results 1. GSTM1-02 in GSTM1 gene The relationship between the state site and the risk of bladder cancer is detected by the PCR method, and the GSTM1-02 site has the GSTM1 deletion (null) and the GSTM1 non-deletion. (Non-null) two genotypes. The Non-null genotype was used as the reference, and the distribution of null variant genotype frequency in the case group and the control group was not significant (P0.05) using the x2 test (P0.05). 5% CI = 0.89-1.58). The stratified analysis revealed the frequency of null variant genotypes in the subgroup population of different age, sex, smoking conditions There was no significant difference in distribution (P0.05).2. The PSCA gene rs2294 The relationship between the polymorphism site and the risk of bladder cancer was detected by x2 test, and the C/ T and T/ T mutation genotypes were found in the case group and the control group. There was a significant difference in the frequency distribution in the middle (P0.05). The C/ C genotype as the reference, the multi-factor non-conditional logistic regression analysis showed that the risk of C/ T and T/ T variant genotypes was significantly associated with the risk of bladder cancer (corrected OR = 1.54,95% CI = 1.15-2.06), and there was a significant dose between the risk allele T and the incidence of bladder cancer. -Reaction relationship (Ptrs = 0.001). The risk of bladder cancer in individuals carrying C/ T and T/ T mutation genotypes at age 65 (corrected OR = 1.80,95% CI = 1.17-2.75), male (corrected OR = 1.57,95% CI = 1.14-2.18), smoking (corrected OR = 1.79,95% CI = 1.15-2.80) There was a more significant increase in the subgroup population (P0.05). The further gene-environment interaction analysis did not find the PSCA group Due to the interaction with the environment (P0.05).3. GSTM1-02 and rs229 The relationship between the polymorphism site of the 4008 and the pathological stage and the grade of the bladder cancer was found by Fisher's exact probability method, and the mutation genotype of GSTM1 and PSCA in the case group of bladder cancer There was no significant difference in the distribution of stage and grade (P0.05).4. GSTM1 The relationship between the polymorphic site of-02 and rs2294008 and the recurrence of bladder cancer was found by x2 test, and the mutation groups of GSTM1 and PSCA There was no significant difference in the distribution of the non-recurrent group and the non-recurrent group (P0.05). in that present invention, The frequency distribution of each variant genotype was not significantly different (P0.05). Conclusion 1. GSTM1 gene GST The deletion of the base of the M1-02 locus is not related to the genetic susceptibility of the bladder cancer in the Chinese Han population. The risk of a group of bladder cancer, especially in the age of 65, is more pronounced in the male and in the smoking subgroup.3. The base of the GSTM1-02 site is missing and rs2 There was no significant correlation between the polymorphism of the 24008 site and the pathological staging and grade of bladder cancer in the Han population of China.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.14
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