雄激素受体基因（CAG）_n重复多态性与前列腺癌患病风险相关性研究
发布时间：2019-03-25 07:54
【摘要】：第一部分雄激素受体基因(CAG)n重复多态性与中国北方人群前列腺癌患病风险相关性的病例对照研究 目的研究雄激素受体(AR)基因(CAG)n重复多态性与中国北方人群前列腺癌(PCa)患病风险的关系。 材料和方法回顾性分析中国北方地区PCa患者140例和按年龄匹配的健康男性206例,记录受试者临床信息并用盐析法提取外周血基因组DNA。利用荧光标记引物PCR扩增AR基因第一外显子,毛细管电泳法进行基因分型,然后用Sanger法直接测序验证分型结果。根据基因分型结果推算(CAG)n重复次数。比较AR基因(CAG)。重复次数在PCa组和对照组的分布差异,并分析(CAG)n重复多态性与PCa患者年龄、体重指数(BMI)、前列腺特异抗原(PSA、Gleason评分和临床病理分期的关系。PCa组和对照组间均数比较采用独立样本t检验或秩和检验,两组基因型频率分布差异的比较采用Z检验,计算比值比(OR)及其95%置信区间(95%CI),P0.05认为具有统计学意义。统计学分析采用SPSS19.0软件完成。 结果最终纳入具有完整临床资料和基因分型结果的研究对象共323例,PCa组126例,对照组197例。两组受试者的年龄和BMI无显著性差异(P0.05)。PCa组AR基因(CAG)n平均重复次数为19.81±3.30,对照组(CAG)。平均重复次数为20.58±2.75,PCa组(CAG)。平均重复次数明显少于对照组(P0.05)。短(CAG)。重复(20次)序列AR基因的分布频率在PCa组明显高于对照组(OR=1.70,95%CI:1.06,2.71,P0.05)；且短(CAG)。重复序列是发生高级别(Gleason评分7分)PCa的危险因素(OR=4.12,95%CI:1.84,9.23, P0.01)。AR基因(CAG)。重复多态性在不同年龄、BMI、PSA和临床病理分期的PCa患者中分布无显著性差异(P0.05)。 结论AR基因(CAG)n重复多态性与中国北方人群PCa患病风险相关；短(CAG)。重复(20次)序列会增加PCa患病风险,且与高级别PCa的发生具有一定相关性。 第二部分雄激素受体基因(CAG)n重复多态性与多人群前列腺癌患病风险相关性的Meta分析 目的用Meta分析的方法研究雄激素受体基因(CAG)n重复多态性与多人群前列腺癌患病风险的相关性。 材料和方法检索2013年8月之前国内外大型数据库中关于AR基因(CAG)n重复多态性与PCa患病风险关系研究的文献。制定文献纳入和排除标准进行筛选,并加入第一部分研究数据。采取双人盲法提取文献数据,用Stata12.0软件Meta分析模块完成分析。首先采用Q检验分析各研究之间的异质性,进行亚组分析挖掘异质性来源。然后采用Mantel-Haenszel固定效应模型或随机效应模型合并效应量分析,计算OR值和95%CI评价AR基因(CAG)n重复多态性与PCa患病风险的相关性,进而按照研究人群种族进行亚组分析。并进行敏感性分析和累积分析评价Meta分析结果的稳定性。最后采用Begg's检验和Egger's检验及绘制漏斗图的方法评估潜在发表偏倚,采用剪补法识别和处理潜在发表偏倚。 结果检索到相关文献215篇,入选31篇加上我们的研究进行Meta分析。研究人群包括高加索人、亚洲人、非洲人和西班牙人,其中PCa组5,516例、健康对照组6,834例。各研究间存在明显异质性(I2=76.2%,P0.05),其中以非洲人(I2=88.0%)和亚洲人(I2=81.5%)为研究对象的研究间异质性较大。采用随机效应模型进行合并效应量分析显示,短(CAG)n重复序列AR基因显著增加PCa患病风险(OR=1.61,95%CI：1.34,1.94)。亚组分析提示,短(CAG)。重复序列与高加索人(OR=1.37,95%CI：1.15,1.63)和亚洲人(OR=2.10,95%CI:1.38,3.19) PCa患病风险增加具有显著相关性,而与非洲人和西班牙人PCa患病风险的相关性不明显。敏感性分析和累计分析提示本项Meta分析结果较为稳定。尽管Begg's检验和Egger's检验均提示存在显著发表偏倚(P0.05),但用剪补法剪补前后的合并效应量OR值无显著性差异。 结论AR基因(CAG)n重复多态性与PCa患病风险的关系受到人群种族的影响,短(CAG)n重复序列与高加索人和亚洲人PCa患病风险增加呈正相关性；但与非洲人和西班牙人PCa患病风险无明显相关性。
[Abstract]:A case-control study on the association between the repeat polymorphism of the first part of the androgen receptor gene (CAG) and the risk of prostate cancer in the northern Chinese population Objective To study the relationship between the repeat polymorphism of androgen receptor (AR) gene (CAG) and the risk of prostate cancer (PCa) in the northern Chinese population. Materials and Methods: A retrospective analysis of 140 healthy men with PCa in northern China and 206 healthy men matched by age. The clinical information of the subject was recorded and the peripheral blood genome was extracted by salting-out method. and the first exon of the AR gene is amplified by using the fluorescent labeling primer PCR, the gene typing is carried out by the capillary electrophoresis method, Type results. (CAG) n weight is calculated according to the genotyping results Number of times. Comparison of AR gene (C AG). The number of repeat times in the PCa group and the control group was different, and the (CAG) n repeat polymorphism was associated with the age, body mass index (BMI), prostate specific antigen (PSA, Gleason score, and clinical pathology) of the PCa patient. The relationship between the control group and the control group was the independent sample t test or the rank sum test. The comparison of the frequency distribution of the two groups was the Z test, the ratio ratio (OR) and the 95% confidence interval (95% CI), and the difference between the two groups was considered to have statistical significance. Significance of study. Statistical analysis using SPSS19.0 soft The results were included in 323 patients with complete clinical data and genotyping results,126 in the PCa group, and 126 in the control group. In group 197, there was no significant difference in age and BMI between the two groups (P0.05). The average number of repeat times of AR gene (CAG) n in the PCa group was 19.81 to 3.30, and the control group (CAG). The average number of repetitions is 20.58, 2.75, and the PCa group (CAG). The average number of repetitions was significantly lower than that in the control group (P 0.05). Short (CAG). The distribution frequency of the repeat (20) sequence AR gene was significantly higher in the PCa group than in the control group (OR = 1.70,95% CI: 1.06, 2.71, P0.05); and (CAG). The repeat sequence was a risk factor for the high-level (Gleason score 7 score) PCa (OR = 4.12,95% CI: 1.84, 9.23, P 0.01). AR gene (CAG). There was no significant difference in the distribution of repeat polymorphisms in PCa patients with different age, BMI, PSA and clinical pathology (P Conclusion The repeat polymorphism of AR gene (CAG) n is related to the risk of PCa in the northern Chinese population. ; Short (CAG). The repeated (20) sequence increases the risk of PCa and is associated with the occurrence of high-level PCa The second part of the androgen receptor gene (CAG) n repeat polymorphism and the risk of the multiple population of prostate cancer Meta-analysis of the correlation: A meta-analysis was used to study the repeat polymorphism of the androgen receptor gene (CAG) n and the multi-population The correlation of the risk of the disease in the column adenocarcinoma. Materials and methods retrieve the repeat polymorphism of AR gene (CAG) n and P in the large database at home and abroad by August 2013. The literature of the study on the relationship between the risk of the disease of Ca. The criteria for inclusion and exclusion of the literature are to be established Select and join the first part of the study data. Take the double blind method to extract the literature data and use the Stata2.0 soft A meta-analysis module was used to complete the analysis. The heterogeneity of each study was first analyzed by Q-test. The heterogeneous origin of the subgroup analysis was carried out. The correlation between the OR value and the 95% CI evaluation of the AR gene (CAG) n repeat polymorphism and the risk of PCa disease was then calculated using the Mantel-Haenszel fixed effect model or the random effect model combined effects analysis, and further by Subgroup analysis of the population of the study population was performed and a sensitivity analysis and a cumulative analysis were conducted The stability of the results of the meta-analysis of the price is evaluated. Finally, the method of checking and drawing the funnel diagram by the Beg's test and the Egger's test and drawing the funnel diagram is used to evaluate the potential published bias. The potential publication bias was identified and processed by the complementary method. The results were retrieved to the relevant literature 215 and included in 31 articles. Add our study to a meta-analysis. The study population includes the Caucasian, Asian, African and Spanish, of which the Group of PCa 5,5 There were 6 and 834 healthy controls. There was a significant heterogeneity among the study groups (I2 = 76.2%, P0.05). Among them, Africans (I2 = 88.0%) and Asian (I2 = 81.5%) The results showed that the AR gene of the short (CAG) n repeated sequence significantly increased the risk of PCa (OR = 1.61,9). 5% CI: 1.34, 1.94 ). The subgroup analysis indicated a short (CAG). The repeat sequence had a significant correlation with the increase in the risk of increased risk of PCa in the Caucasian (OR = 1.37,95% CI: 1.15, 1.63) and in the Asian (OR = 2.10,95% CI: 1.38, 3.19), compared to Africans and Spain. The correlation between the risk of human PCa disease is not obvious. Sensitivity analysis and cumulative analysis The results of this meta-analysis were stable, although the results of the Beg's test and the Egger's test showed significant bias (P0.05). Conclusion The association of AR gene (CAG) n-repeat polymorphism with the risk of PCa is affected by the race of the population, and the short (CAG) n-repeat sequence is positively related to the increase of the risk of PCa in the Caucasian and Asian.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R737.25
本文编号：2446788
[Abstract]:A case-control study on the association between the repeat polymorphism of the first part of the androgen receptor gene (CAG) and the risk of prostate cancer in the northern Chinese population Objective To study the relationship between the repeat polymorphism of androgen receptor (AR) gene (CAG) and the risk of prostate cancer (PCa) in the northern Chinese population. Materials and Methods: A retrospective analysis of 140 healthy men with PCa in northern China and 206 healthy men matched by age. The clinical information of the subject was recorded and the peripheral blood genome was extracted by salting-out method. and the first exon of the AR gene is amplified by using the fluorescent labeling primer PCR, the gene typing is carried out by the capillary electrophoresis method, Type results. (CAG) n weight is calculated according to the genotyping results Number of times. Comparison of AR gene (C AG). The number of repeat times in the PCa group and the control group was different, and the (CAG) n repeat polymorphism was associated with the age, body mass index (BMI), prostate specific antigen (PSA, Gleason score, and clinical pathology) of the PCa patient. The relationship between the control group and the control group was the independent sample t test or the rank sum test. The comparison of the frequency distribution of the two groups was the Z test, the ratio ratio (OR) and the 95% confidence interval (95% CI), and the difference between the two groups was considered to have statistical significance. Significance of study. Statistical analysis using SPSS19.0 soft The results were included in 323 patients with complete clinical data and genotyping results,126 in the PCa group, and 126 in the control group. In group 197, there was no significant difference in age and BMI between the two groups (P0.05). The average number of repeat times of AR gene (CAG) n in the PCa group was 19.81 to 3.30, and the control group (CAG). The average number of repetitions is 20.58, 2.75, and the PCa group (CAG). The average number of repetitions was significantly lower than that in the control group (P 0.05). Short (CAG). The distribution frequency of the repeat (20) sequence AR gene was significantly higher in the PCa group than in the control group (OR = 1.70,95% CI: 1.06, 2.71, P0.05); and (CAG). The repeat sequence was a risk factor for the high-level (Gleason score 7 score) PCa (OR = 4.12,95% CI: 1.84, 9.23, P 0.01). AR gene (CAG). There was no significant difference in the distribution of repeat polymorphisms in PCa patients with different age, BMI, PSA and clinical pathology (P Conclusion The repeat polymorphism of AR gene (CAG) n is related to the risk of PCa in the northern Chinese population. ; Short (CAG). The repeated (20) sequence increases the risk of PCa and is associated with the occurrence of high-level PCa The second part of the androgen receptor gene (CAG) n repeat polymorphism and the risk of the multiple population of prostate cancer Meta-analysis of the correlation: A meta-analysis was used to study the repeat polymorphism of the androgen receptor gene (CAG) n and the multi-population The correlation of the risk of the disease in the column adenocarcinoma. Materials and methods retrieve the repeat polymorphism of AR gene (CAG) n and P in the large database at home and abroad by August 2013. The literature of the study on the relationship between the risk of the disease of Ca. The criteria for inclusion and exclusion of the literature are to be established Select and join the first part of the study data. Take the double blind method to extract the literature data and use the Stata2.0 soft A meta-analysis module was used to complete the analysis. The heterogeneity of each study was first analyzed by Q-test. The heterogeneous origin of the subgroup analysis was carried out. The correlation between the OR value and the 95% CI evaluation of the AR gene (CAG) n repeat polymorphism and the risk of PCa disease was then calculated using the Mantel-Haenszel fixed effect model or the random effect model combined effects analysis, and further by Subgroup analysis of the population of the study population was performed and a sensitivity analysis and a cumulative analysis were conducted The stability of the results of the meta-analysis of the price is evaluated. Finally, the method of checking and drawing the funnel diagram by the Beg's test and the Egger's test and drawing the funnel diagram is used to evaluate the potential published bias. The potential publication bias was identified and processed by the complementary method. The results were retrieved to the relevant literature 215 and included in 31 articles. Add our study to a meta-analysis. The study population includes the Caucasian, Asian, African and Spanish, of which the Group of PCa 5,5 There were 6 and 834 healthy controls. There was a significant heterogeneity among the study groups (I2 = 76.2%, P0.05). Among them, Africans (I2 = 88.0%) and Asian (I2 = 81.5%) The results showed that the AR gene of the short (CAG) n repeated sequence significantly increased the risk of PCa (OR = 1.61,9). 5% CI: 1.34, 1.94 ). The subgroup analysis indicated a short (CAG). The repeat sequence had a significant correlation with the increase in the risk of increased risk of PCa in the Caucasian (OR = 1.37,95% CI: 1.15, 1.63) and in the Asian (OR = 2.10,95% CI: 1.38, 3.19), compared to Africans and Spain. The correlation between the risk of human PCa disease is not obvious. Sensitivity analysis and cumulative analysis The results of this meta-analysis were stable, although the results of the Beg's test and the Egger's test showed significant bias (P0.05). Conclusion The association of AR gene (CAG) n-repeat polymorphism with the risk of PCa is affected by the race of the population, and the short (CAG) n-repeat sequence is positively related to the increase of the risk of PCa in the Caucasian and Asian.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R737.25
【参考文献】
相关期刊论文 前2条
1 刘元丰,江军,王洛夫,王亚林,张尧;雄激素受体基因多态性与前列腺癌关系的研究[J];第三军医大学学报;2005年10期
2 Tomomi Kimura;;East meets West: ethnic differences in prostate cancer epidemiology between East Asians and Caucasians[J];癌症;2012年09期
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