GSTM1、PSCA基因多態(tài)性與膀胱癌發(fā)病風(fēng)險的關(guān)系
發(fā)布時間：2019-06-03 02:03
【摘要】：目的 研究中國漢族人群谷胱甘肽轉(zhuǎn)硫酶M1基因(Glutathione-S-transferase M1, GSTM1)GSTM1-02位點和前列腺干細(xì)胞抗原基因(Prostate Stem Cell Antigen, PSCA) rs2294008位點的多態(tài)性與膀胱尿路上皮細(xì)胞癌(BUCC)發(fā)病風(fēng)險、病理分期分級及腫瘤復(fù)發(fā)之間的關(guān)系。 方法 采用病例-對照研究的方法,收集中國漢族膀胱尿路上皮癌患者358例和正常體檢者434例的血液標(biāo)本,將患者病案中的相關(guān)臨床資料和體檢者體檢時記錄的相關(guān)資料統(tǒng)一輸入Excel數(shù)據(jù)庫,病例組膀胱癌的診斷、病理分期和分級均經(jīng)病理組織學(xué)確定,并對所有患者完成隨訪。提取病例組和對照組的血液基因組DNA,分別采用聚合酶鏈反應(yīng)(PCR)和等位基因特異PCP(Allele-specific PCR, AS-PCR)的方法檢測GSTM1和PSCA的基因多態(tài)性,并通過測序方法驗證PSCA基因的分型結(jié)果。 統(tǒng)計 應(yīng)用SPSS20.0for Windows統(tǒng)計軟件包。采用t檢驗和x2檢驗聯(lián)合分析病例組與對照組在性別、年齡、吸煙狀況上的差異；以擬合優(yōu)度x2檢驗進(jìn)行Hardy-Weinberg平衡檢驗,比較對照人群實際基因型頻率與預(yù)期基因型頻率吻合程度；采用x2檢驗分析GSTM1-02和rs2294008兩位點遺傳變異與膀胱癌發(fā)病之間的關(guān)聯(lián),并計算變異型等位基因的個數(shù)和膀胱癌發(fā)病風(fēng)險的劑量效應(yīng)關(guān)系；通過多因素非條件Logistic回歸控制主要暴露因素對基因遺傳變異效應(yīng)的混雜作用；通過分層分析探討不同亞人群中GSTM1和PSCA基因遺傳變異與膀胱癌發(fā)病及復(fù)發(fā)關(guān)聯(lián)度的不同；采用Fisher確切概率法分析以上兩種基因多態(tài)性與膀胱癌病理分期、分級之間的關(guān)系。比值比(Odd Ratio, OR)和95%置信區(qū)間(Confidence Intervals, CI)表示關(guān)聯(lián)強(qiáng)度。所有檢驗均為雙側(cè)檢驗,檢驗水平a=0.05,P0.05為差異有顯著意義。 結(jié)果 1.GSTM1基因GSTM1-02多態(tài)位點與膀胱癌發(fā)病風(fēng)險的關(guān)系 通過PCR法檢測到GSTM1基因GSTM1-02位點有GSTM1缺失(Null)和GSTM1非缺失(Non-null)兩種基因型。以Non-null基因型為參照,采用x2檢驗發(fā)現(xiàn)Null變異基因型頻率在病例組和對照組的分布差異無顯著性(P0.05,校正OR=1.19,95%CI=0.89-1.58)。分層分析顯示,在不同年齡、性別、吸煙狀況的亞組人群中,Null變異基因型的頻率分布亦無顯著差異(P0.05)。 2.PSCA基因rs2294008多態(tài)位點與膀胱癌發(fā)病風(fēng)險的關(guān)系 通過x2檢驗發(fā)現(xiàn)C/T和T/T變異基因型在病例組和對照組中的頻率分布存在明顯差異(P0.05)。以C/C基因型為參照,多因素非條件Logistic回歸分析顯示,C/T和T/T變異基因型攜帶者與膀胱癌的風(fēng)險性上升有顯著性關(guān)聯(lián)(校正OR=1.54,95%CI=1.15-2.06),而且風(fēng)險等位基因T與膀胱癌發(fā)病之間具有顯著的劑量-反應(yīng)關(guān)系(Ptrend=0.001)。分層分析顯示,攜帶C/T和T/T變異基因型的個體發(fā)生膀胱癌的風(fēng)險性在年齡65歲(校正OR=1.80,95%CI=1.17-2.75)、男性(校正OR=1.57,95%CI=1.14-2.18)、吸煙(校正OR=1.79,95%CI=1.15-2.80)的亞組人群中增加更為顯著(P0.05)。進(jìn)一步的基因-環(huán)境的交互作用分析未發(fā)現(xiàn)PSCA基因與環(huán)境之間存在交互作用(P0.05)。 3.GSTM1-02和rs2294008多態(tài)位點與膀胱癌病理分期、分級的關(guān)系 采用Fisher確切概率法發(fā)現(xiàn),GSTM1和PSCA的變異基因型在病例組膀胱癌病理各分期、分級中的分布均無明顯差異(P0.05)。 4.GSTM1-02和rs2294008多態(tài)位點與膀胱癌復(fù)發(fā)的關(guān)系 經(jīng)x2檢驗發(fā)現(xiàn),GSTM1和PSCA的變異基因型在復(fù)發(fā)組和未復(fù)發(fā)組的分布均無明顯差異(P0.05)。分層分析顯示,在不同年齡、性別、吸煙狀況的亞組人群中,各變異基因型的頻率分布亦均無顯著差異(P0.05)。 結(jié)論 1.GSTM1基因GSTM1-02位點堿基缺失與中國漢族人群膀胱癌遺傳易感性無明顯相關(guān)。 2. PSCA基因rs2294008位點遺傳變異可顯著增加中國漢族人群罹患膀胱癌的危險性,尤其是在年齡65歲、男性、吸煙亞組中更為顯著。 3. GSTM1-02位點堿基缺失和rs2294008位點多態(tài)性與中國漢族人群膀胱癌病理分期、分級均無顯著性相關(guān)。 4. GSTM1-02位點堿基缺失和rs2294008位點多態(tài)性與中國漢族人群膀胱癌復(fù)發(fā)均無顯著性相關(guān)。
[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.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.14
本文編號：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.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.14
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