雄激素受體基因（CAG）_n重復(fù)多態(tài)性與前列腺癌患病風(fēng)險(xiǎn)相關(guān)性研究
發(fā)布時(shí)間：2019-03-25 07:54
【摘要】：第一部分雄激素受體基因(CAG)n重復(fù)多態(tài)性與中國(guó)北方人群前列腺癌患病風(fēng)險(xiǎn)相關(guān)性的病例對(duì)照研究 目的研究雄激素受體(AR)基因(CAG)n重復(fù)多態(tài)性與中國(guó)北方人群前列腺癌(PCa)患病風(fēng)險(xiǎn)的關(guān)系。 材料和方法回顧性分析中國(guó)北方地區(qū)PCa患者140例和按年齡匹配的健康男性206例,記錄受試者臨床信息并用鹽析法提取外周血基因組DNA。利用熒光標(biāo)記引物PCR擴(kuò)增AR基因第一外顯子,毛細(xì)管電泳法進(jìn)行基因分型,然后用Sanger法直接測(cè)序驗(yàn)證分型結(jié)果。根據(jù)基因分型結(jié)果推算(CAG)n重復(fù)次數(shù)。比較AR基因(CAG)。重復(fù)次數(shù)在PCa組和對(duì)照組的分布差異,并分析(CAG)n重復(fù)多態(tài)性與PCa患者年齡、體重指數(shù)(BMI)、前列腺特異抗原(PSA、Gleason評(píng)分和臨床病理分期的關(guān)系。PCa組和對(duì)照組間均數(shù)比較采用獨(dú)立樣本t檢驗(yàn)或秩和檢驗(yàn),兩組基因型頻率分布差異的比較采用Z檢驗(yàn),計(jì)算比值比(OR)及其95%置信區(qū)間(95%CI),P0.05認(rèn)為具有統(tǒng)計(jì)學(xué)意義。統(tǒng)計(jì)學(xué)分析采用SPSS19.0軟件完成。 結(jié)果最終納入具有完整臨床資料和基因分型結(jié)果的研究對(duì)象共323例,PCa組126例,對(duì)照組197例。兩組受試者的年齡和BMI無顯著性差異(P0.05)。PCa組AR基因(CAG)n平均重復(fù)次數(shù)為19.81±3.30,對(duì)照組(CAG)。平均重復(fù)次數(shù)為20.58±2.75,PCa組(CAG)。平均重復(fù)次數(shù)明顯少于對(duì)照組(P0.05)。短(CAG)。重復(fù)(20次)序列AR基因的分布頻率在PCa組明顯高于對(duì)照組(OR=1.70,95%CI:1.06,2.71,P0.05)；且短(CAG)。重復(fù)序列是發(fā)生高級(jí)別(Gleason評(píng)分7分)PCa的危險(xiǎn)因素(OR=4.12,95%CI:1.84,9.23, P0.01)。AR基因(CAG)。重復(fù)多態(tài)性在不同年齡、BMI、PSA和臨床病理分期的PCa患者中分布無顯著性差異(P0.05)。 結(jié)論AR基因(CAG)n重復(fù)多態(tài)性與中國(guó)北方人群PCa患病風(fēng)險(xiǎn)相關(guān)；短(CAG)。重復(fù)(20次)序列會(huì)增加PCa患病風(fēng)險(xiǎn),且與高級(jí)別PCa的發(fā)生具有一定相關(guān)性。 第二部分雄激素受體基因(CAG)n重復(fù)多態(tài)性與多人群前列腺癌患病風(fēng)險(xiǎn)相關(guān)性的Meta分析 目的用Meta分析的方法研究雄激素受體基因(CAG)n重復(fù)多態(tài)性與多人群前列腺癌患病風(fēng)險(xiǎn)的相關(guān)性。 材料和方法檢索2013年8月之前國(guó)內(nèi)外大型數(shù)據(jù)庫中關(guān)于AR基因(CAG)n重復(fù)多態(tài)性與PCa患病風(fēng)險(xiǎn)關(guān)系研究的文獻(xiàn)。制定文獻(xiàn)納入和排除標(biāo)準(zhǔn)進(jìn)行篩選,并加入第一部分研究數(shù)據(jù)。采取雙人盲法提取文獻(xiàn)數(shù)據(jù),用Stata12.0軟件Meta分析模塊完成分析。首先采用Q檢驗(yàn)分析各研究之間的異質(zhì)性,進(jìn)行亞組分析挖掘異質(zhì)性來源。然后采用Mantel-Haenszel固定效應(yīng)模型或隨機(jī)效應(yīng)模型合并效應(yīng)量分析,計(jì)算OR值和95%CI評(píng)價(jià)AR基因(CAG)n重復(fù)多態(tài)性與PCa患病風(fēng)險(xiǎn)的相關(guān)性,進(jìn)而按照研究人群種族進(jìn)行亞組分析。并進(jìn)行敏感性分析和累積分析評(píng)價(jià)Meta分析結(jié)果的穩(wěn)定性。最后采用Begg's檢驗(yàn)和Egger's檢驗(yàn)及繪制漏斗圖的方法評(píng)估潛在發(fā)表偏倚,采用剪補(bǔ)法識(shí)別和處理潛在發(fā)表偏倚。 結(jié)果檢索到相關(guān)文獻(xiàn)215篇,入選31篇加上我們的研究進(jìn)行Meta分析。研究人群包括高加索人、亞洲人、非洲人和西班牙人,其中PCa組5,516例、健康對(duì)照組6,834例。各研究間存在明顯異質(zhì)性(I2=76.2%,P0.05),其中以非洲人(I2=88.0%)和亞洲人(I2=81.5%)為研究對(duì)象的研究間異質(zhì)性較大。采用隨機(jī)效應(yīng)模型進(jìn)行合并效應(yīng)量分析顯示,短(CAG)n重復(fù)序列AR基因顯著增加PCa患病風(fēng)險(xiǎn)(OR=1.61,95%CI：1.34,1.94)。亞組分析提示,短(CAG)。重復(fù)序列與高加索人(OR=1.37,95%CI：1.15,1.63)和亞洲人(OR=2.10,95%CI:1.38,3.19) PCa患病風(fēng)險(xiǎn)增加具有顯著相關(guān)性,而與非洲人和西班牙人PCa患病風(fēng)險(xiǎn)的相關(guān)性不明顯。敏感性分析和累計(jì)分析提示本項(xiàng)Meta分析結(jié)果較為穩(wěn)定。盡管Begg's檢驗(yàn)和Egger's檢驗(yàn)均提示存在顯著發(fā)表偏倚(P0.05),但用剪補(bǔ)法剪補(bǔ)前后的合并效應(yīng)量OR值無顯著性差異。 結(jié)論AR基因(CAG)n重復(fù)多態(tài)性與PCa患病風(fēng)險(xiǎn)的關(guān)系受到人群種族的影響,短(CAG)n重復(fù)序列與高加索人和亞洲人PCa患病風(fēng)險(xiǎn)增加呈正相關(guān)性；但與非洲人和西班牙人PCa患病風(fēng)險(xiǎn)無明顯相關(guān)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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.25
本文編號(hào)：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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.25
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
1 劉元豐,江軍,王洛夫,王亞林,張堯;雄激素受體基因多態(tài)性與前列腺癌關(guān)系的研究[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2005年10期
2 Tomomi Kimura;;East meets West: ethnic differences in prostate cancer epidemiology between East Asians and Caucasians[J];癌癥;2012年09期
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