41个单核苷酸多态性位点与睾丸生殖细胞瘤的相关性研究

目的:通过对76例睾丸生殖细胞肿瘤(TGCTs)患者与148例健康体检人群41个相关基因单核苷酸多态性(SNPs)位点进行病例对照研究,期望发现国内TGCTs患者的遗传易感基因及位点,为临床预测、诊治TGCTs提供新途径。方法:选取国外文献发现的TGCTs患者易感基因的41个SNPs位点,作为本实验待测位点。采用i MLDRTM分析方法,将76例TGCTs患者及148例健康体检人群血液样本进行待测位点分型检测。结果:在我国,ESR2基因的rs2978381、rs10146204、rs12435857、rs1256063位点,ESR1基因的rs9397080位点,PTEN基因的rs11202586位点,CYP1A1基因的rs2606345、rs4646903位点和CYP19A1基因的rs1456432位点与TGCTs相关。结论:本研究中TGCTs患者的相关SNPs位点与国外TGCTs人群存在差异,国内TGCTs患者的相关SNPs位点也不完全相同。     

雌激素受体β的单核苷酸多态性与前列腺癌风险的相关性研究

目的研究雌激素受体β(ERβ)的单核苷酸多态性(SNPs)与前列腺癌(CaP)风险的相关性。方法对40例CaP患者和86例正常对照者利用直接测序法对ERβ基因中的4个SNPs(近端启动子上游的3个SNPsrs3829768,rs1271572,rs3841304和外显子7上的SNPsrs1256049)进行基因分型,分析单个位点的等位基因和基因频率是否与CaP相关。结果由于不符合HardyWeinberg平衡,SNP位点rs3841304被排除。发现在CaP患者中,近端启动子上游的SNPs位点rs3829768(A/G)的G和rs1271572(C/A)的A等位基因频率及其基因型频率均显著低于正常对照者(P<0.01)。结论ERβ基因近端启动子上游有2个SNPs与汉族CaP之间存在显著的相关性。     

巨噬细胞清道夫受体单核苷酸多态性与前列腺癌易感及患者预后的相关性分析

目的探讨分析巨噬细胞清道夫受体(MSR1)单核苷酸多态性与前列腺癌易感及患者治疗预后的相关性。方法选择2017年3月至2019年5月在本院治疗的前列腺癌患者103例设为前列腺癌组,再选取同期在本院健康体检的男性受试者97例设为对照组。检测两组受试者MSRI基因r918位点及rs1904577位点的基因多态性分布情况,并分析前列腺癌化疗相关因素及MSRI基因rs918.rs1904577位点与前列腺癌患者生存预后的关系。结果两组受试者MISRI基因rs918位点基因型GG、AG.AA比较,差异具有统计学意义(P<0.05),携带AG、AA基因型者相对于携带GG基因型者罹患前列腺癌的OR值分别为1.364.7.941;两组受试者MSRI基因rs1904577位点基因型GG,AG.AA比较,差异具有统计学意义(P<0.05),携带AG、AA基因型者相对于携带GG基因型者罹患前列腺癌的OR值分别为1.819.8.228。对可能影响患者化疗疗效的各因素进行单因素及多因素logstie回归分析,其中T分期.CGleason评分以及MSRI基因rs1904577位点基因型进人回归模型(P<0.05),是影响患者化疗疗效的重要因素。MSR1基因rs918位点CG以及AG+AA基因型前列腺癌患者生存情况比较,差异无统计学意义(P>0.05)。MSRI基因rs1904577位点GG基因型前列腺癌患者生存情况显著优于AG+AA基因型患者(P<0.05)。结论MSR1基因ns918位点和rs1904577位点单核苷酸多态性与前列腺癌易感性相关,其中rs1904577位点单核苷酸多态性与患者化疗的疗效及生存预后有关。     

EZH2基因多态性与中国女性乳腺癌易感性的分析

目的探讨Zeste同源物增强子2(EZH2)基因的单核苷酸多态性(SNPs)与乳腺癌发生风险之间的关系。方法纳入在全国22家三级甲等医院就诊的1 039例乳腺癌患者和1 040例对照者。检测3个EZH2基因SNPs位点(rs2302427 C>G、rs12670401 T>C和rs6464926 C>T)的基因型分布情况以及不同基因型与乳腺癌发生风险的相关性。使用数据库乳腺癌数据分析EZH2在乳腺癌组织中的表达情况及其与患者预后的关系。结果 EZH2 rs6464926 CC基因型与TT基因型(OR=1.362, P=0.015)和显性模型(OR=1.22, P=0.045)乳腺癌发病风险相比差异具有统计学意义。亚组分析表明, 在BMI≥24 kg/m2的女性中, 与野生型相比, rs6464926位点TC基因型(P=0.050)、TT基因型(P=0.025)和显性模型(TC+TT, P=0.021)患乳腺癌风险差异具有统计学意义。rs6464926位点与EZH2基因表达具有相关性(P=6.89E-47)。EZH2基因在乳腺癌组织中高表达(P<0.001), 并...     

基因测序筛选前列腺癌患者PCA3(DD3)基因外显子多态性

目的 筛查前列腺癌患者PCA3基因外显子单核苷酸多态性位点,初步探讨PCA3基因多态性与前列腺癌的相关性.方法 采用基因测序法对41例前列腺癌(PCa)患者和40例良性前列腺增生(BPH)患者进行PCA3基因外显子SNP位点的筛选,对筛选到的sNP位点进行前列腺癌的相关性分析.结果 PcA3基因外显子1、外显子3、外显子4区域均未检测到基因多态性位点,PCA3基因外显子2区域存在1个SNP位点(A→C),基因型分别为AA型、AC型、CC型,该位点的基冈型频率和等位基因频率与前列腺癌存在相关性(P<0.05).结论 基因测序可有效筛选到PCA3基因外显子的SNP位点,PCA3基因外显子2基因多态性可能与前列腺癌发病风险有关.     

睾酮5-α还原酶Ⅱ基因V89L多态性与前列腺癌预后关系的研究

目的:探讨睾酮5-α还原酶Ⅱ(SRD5A2)基因V89L多态性与影响前列腺癌预后因素的关系。方法:对V89L多态性位点用Rsa-1限制性内切酶进行酶切鉴定,观察112例前列腺癌患者和89例BPH患者的V89L(VV、VL、LL)多态性分布情况的差异及其多态性与前列腺癌患者年龄、前列腺特异性抗原(PSA)、游离PSA/总PSA值(tPSA/fPSA,F/T)、Gleason评分、临床分期的关系。结果:前列腺癌组112例与BPH组89例的V89L基因频度风险无显著性差异(χ2=3.606,df=2,P=0.165)。前列腺癌组VV和VL+LL基因型与fPSA、tPSA、F/T、T分期、Gleason评分差异无显著性(P>0.05)。VV和VL+LL各评价预后指标差异无显著性(P>0.05)。分段评价PSA水平、Gleason评分、临床分期、年龄,均与两种基因型无相关性(P>0.05)。结论:V89L多态性与预后无明显关系,但是可能与前列腺癌的风险存在间接的关系。     

CYP1A1 rs4646422单核甘酸多态性与中国汉族男性不育的相关性研究

目的:探讨中国汉族男性不育与细胞色素P4501A1基因(CYP1A1)rs4646422位点(GA)单核苷酸多态性之间的相关性。方法:采用病例-对照研究方法,应用Mass ARRAY i PLEX GOLD技术对636例[年龄21~49(29.42±5.09)岁]男性不育患者与442例[年龄23~47(28.62±4.46)岁]正常生育男性的CYP1A1 rs4646422位点进行基因分型,利用SPSS软件统计基因型及等位基因频率在男性不育组和正常生育组中分布特点。结果:与野生纯合型GG比较,杂合型AG(OR=1.06,95%CI:0.81~1.38)和纯合突变型AA(OR=1.11,95%CI:0.56~2.21)与男性不育无相关性。将突变型等位基因A(OR=1.06,95%CI:0.85~1.32)与野生型等位基因G进行比较,同样显示与男性不育无关联。结论:CYP1A1基因(rs4646422)单核甘酸的多态性可能与中国汉族男性不育之间不存在相关性。     

肾细胞癌患者VEGFR3基因及CYP3A5*1基因单核苷酸多态性研究

目的:分析VEGFR3基因及CYP3A5*1基因单核苷酸多态性(SNP)在肾癌人群的分布特征,评价其与舒尼替尼药物治疗疗效及耐受性的相关性。方法:2012年6月~2013年6月,对198例肾癌患者进行外周血VEGFR3(rs307826)及CYP3A5*1(rs776746)位点的SNP检测,同时采集患者的自然信息、临床资料、治疗经过及预后。应用统计学方法评价中国人群与欧洲人群这两个基因位点SNP分布差异以及两个基因位点的SNP特征与舒尼替尼治疗晚期肾癌的疗效及耐受性的相关性。结果:VEGFR3(rs307826)位点SNP检测结果:野生型纯合子196例、杂合子2例;CYP3A5*1(rs776746)位点SNP检测结果:野生型纯合子115例、杂合子80例,与欧洲人群分布特征的差异有统计学意义(P0.01)。45例患者接受舒尼替尼药物治疗,CYP3A5*1(rs776746)SNP结果:野生型纯合子27例、杂合子18例,舒尼替尼初始剂量均为50mg/d,4/2周给药方案,主要不良反应包括高血压、血小板减低、白细胞减低、甲状腺功能低下等,Ⅲ~Ⅳ级不良反应发生率28.9%,15例患者因不良反应进行了剂量调整。结论:VEGFR3基因及CYP3A5*1基因的SNP分布特征在不同种族存在显著差异,CYP3A5*1(rs776746)位点SNP特征与中国肾癌患者接受舒尼替尼治疗的Ⅲ~Ⅳ级不良反应发生率及药物减量风险相关。     

云南汉族非综合征性唇腭裂与p53基因多态性的相关性研究

目的:分析p53基因单核苷酸多态性(SNPs)位点的多态性,探究云南汉族非综合征性唇腭裂与p53基因的相关性。方法:选取2016年1月-2018年12月于笔者医院就诊的非综合征性唇腭裂患儿100例为试验组,选取医院同期无先天性畸形正常患儿100例为对照组。采用Taqman探针荧光定量PCR法对p53基因的SNPs位点rs12947788和rs1042522进行基因分型,并用χ^2检验和Logistic回归分析多态位点与非综合征性唇腭裂的相关性。结果:p53的基因SNPs位点rs12947788的等位基因变体A携带者(AA+GA vs GG)发生非综合征性唇腭裂的风险增加(OR=1.393,95%CI 1.030~1.884,P=0.032)。rs1042522(CC vs CG+GG)增加吸烟者母亲生下NSCL/P患儿的风险(OR=2.561,95%CI=1.146~5.721,P=0.022)。rs12947788(AA+GA vs GG)可明显增加有饮酒史母亲(OR=3.235,95%CI=1.158~9.040,P=0.025)生下NSCL/P患儿的风险。结论:云南汉族人群非综合征性唇腭裂与p53基因rs1042522、rs12947788多态具有一定的相关性。     

代谢酶基因多态性与前列腺癌易感性的关系

目的 :探讨CYP1A1、NAT2基因多态性与前列腺癌易感性的关系。　方法 :应用PCR RFLP、ASA和自动实时荧光定量分析技术 ,分析 5 8例前列腺癌病人和 112例健康对照者CYP1A1和NAT2基因 4个位点的多态性 ,比较前列腺癌病人与对照组间频率差异。　结果 :前列腺癌组Ile Val多态位点各等位基因和基因型频率与对照组比较差异有显著性 (P <0 .0 5 ) ,其中等位基因G和GG基因型使患前列腺癌的危险度分别提高了 1.5 9倍 (P <0 .0 5 )和 3.0 6倍 (P <0 .0 5 ) ;前列腺癌组MspI多态位点各等位基因和基因型频率与对照组比较差异无显著性 (P>0 .0 5 )。前列腺癌组NAT2慢乙酰化基因型频率与对照组比较差异无显著性 (P >0 .0 5 )。　结论 :CYP1A1Ile Val基因多态与前列腺癌的发生可能有关 ,MspI基因多态和NAT2慢乙酰化基因型与前列腺癌的发生可能无关     

前列腺癌发生风险与CYP3A5基因多态性的关系

目的 探讨CYP3A5基因多态性与前列腺癌发生风险和病理特点的关系。方法 采用限制性片段多态性分析法对356例前列腺癌患者和306个男性对照中CYP3A5基因第3内含子多态性进行了研究。结果 在前列腺癌和对照组之间CYP3A5基因型分布差异无显著性(P=0．063)，但两组间CYP3A5*1等位基因的分布差异存在显著性(P=0．025)；与携带CYP3A5*3*3基因型者相比，携带CYP3A5*1等位基因的男性患前列腺癌的风险降低了30％(P=0．026)。在不同分期和分级的前列腺癌患者之间CYP3A5基因型分布差异无显著性(P=0．904和0．986)。结论 CYP3A5基因中的CYP3A5*1等位基因可能与前列腺癌的患病风险降低有关。     

PDLIM5、SLC22A3和NKX3-1基因与前列腺癌患病风险的关联性研究

目的:探索PDLIM5基因(rs17021918,T)、SLC22A3基因(rs9364554,C)和NKX3-1基因(rs1512268,A)与中国人群前列腺癌(PCa)患病风险的关联。方法:采用病例-对照研究,包括124例PCa患者和138例正常对照者,对PDLIM5基因(rs17021918,T)﹑SLC22A3基因(rs9364554,C)和NKX3-1基因(rs1512268,A)进行两组间的等位基因及基因型差异分析,探讨各基因与患者的BMI、Gleason评分、PSA浓度、肿瘤分期、年龄等临床表型之间的关联。采用MDR方法进行基因-基因交互作用分析。结果:①PDLIM5﹑SLC22A3和NKX3-1基因的风险等位基因和基因型的频率在病例组和对照间组间的分布无显著性差异(P>0.05)。②3个位点与PCa的发病年龄、Gleason评分、PSA浓度以及病理分期等指标均无显著相关性(P>0.05)。③采用MDR方法分析PDLIM5基因、SLC22A3基因和NKX3-1基因的3个多态性位点的交互作用发现PDLIM5基因和NKX3-1基因之间,可能不存在有基因-基因交互作用,树状图分析说明PDLIM5基因与NKX3-1基因可能有协同作用。结论:PDLIM5、SLC22A3和NKX3-1基因可能与中国人群PCa患病风险无关联。而PDLIM5基因和NKX3-1基因之间对PCa患病风险的影响可能有协同作用。     

整合素α6、β-微精浆蛋白基因和染色体8q24区与前列腺癌的关联研究

目的 探讨整合素α6(ITGA6)基因(rs12621278,G)、染色体8q24区(rs10086908,T)和β-微精浆蛋白(MSMB)基因(rs10993994,T)与北京市居民中前列腺癌(PCa)的关联,了解PCa患者基因型和表型的关系.方法 收集112例PCa患者临床、遗传、膳食习惯、嗜好等表型,对PCa患者和91名正常对照者的ITGA6基因(rs12621278,G)、染色体8q24区(rs10086908,T)和MSMB基因(rs10993994,T)进行比较,并进行病例组的基因型-表型分析.结果 2组间相比,MSMB基因rs10993994,T风险等位基因频率差异有统计学意义(病例组56.4%,对照组46.2%;P=0.001,OR=1.97,95%CI为1.28～3.04).8q24区的rs10086908,T(病例组83.5%,对照组79.2%)和ITGA6基因的rs12621278,G(病例组27.2%,对照组27.0%)组间差异无统计学意义(P＞0.05).数量性状分析发现ITGA6风险基因型(G/G)的患者病程为(1.40±0.55)年,显著短于A/G型的(4.38±3.10)年和A/A型的(2.37±1.84)年(P=0.003).结论 MSMB基因变异和PCa易感性之间存在相关性,提示MSMB基因可能与PCa有关联.

Abstract：

Objective To explore the correlation between ITGA6 gene (rs12621278, G), MSMB gene (rs10993994, T), chromosome 8q24 (rs10086908, T) and prostate cancer (PCa) in Beijing residents, and to explore the correlation between genotype and phenotype in PCa patients. Methods PCa patient phenotypes were collected including clinical, genetic, dietary habits, hobbies and blood samples. ITGA6 gene (rs12621278, G), chromosome 8q24 (rs10086908, T) and MSMB gene (rs10993994, T) compared the allele distribution between 112 PCa and 91 healthy control age matched patients. The genotype and phenotype analysis was conducted in the 2 groups. Results Between the case and control groups, only rs10993994, T of MSMB gene (case 56.4%,control 46.2%) was significantly different (P=0.001; OR=1.97, 95%CI:1.28-3.04). The rs10086908, T of 8q24 (case 83.5%, control 79.2%) and rs12621278, G of ITGA6 gene (case 27.2%, control 27.0%) were not significantly associated with PCa in the study sample (P>0.05). Quantitative trait analysis showed that the disease duration of ITGA6 risk genotypes (G/G,1.40±0.55 years) in PCa patients was significantly shorter (P=0.003) than the other genotype carriers (A/G, 4.38±3.10 years; A/A, 2.37±1.84 years). Conclusion The genetic variation in MSMB is possibly associated with PCa susceptibility, suggesting that MSMB genes might be associated with PCa in a Chinese population.     

Association of CYP17, GSTP1, and PON1 polymorphisms with the risk of prostate cancer

BACKGROUND: Dietary factors, life-style as well as environmental conditions may contribute to the risk of prostate tumor together with genetic susceptibility, that may be an important factor in determining who is more likely to develop prostate malignancy. We have undertaken a case-control study in order to elucidate the association between polymorphisms in some metabolizing genes with the risk of prostate cancer (PCa). METHODS: Polymorphisms of three xenobiotic genes (CYP17, GSTP1, PON1) were characterized in 384 patients with untreated PCa and 360 age-matched control patients with benign prostatic hyperplasia (BPH). All polymorphisms were investigated by PCR/RFLP methods using DNA from lymphocytes. RESULTS: We found that men with the CYP17/A1A1-A1A2 genotypes, GSTP1/IleVal genotype, PON192/QR and PON55/LM-MM genotypes had a significantly higher risk of PCa compared with the others genotypes. CONCLUSIONS: The three polymorphisms appear to be common genetic traits that are associated with an increased risk for PCa: the analysis of them all in each single case may be a predictable factor, particularly among groups exposed to PCa-related carcinogens.     

Genetic variations in androgen metabolism genes and associations with prostate cancer in South African men

Background. In South Africa white men have the highest incidence of prostate cancer (PCa), coloured (mixed ancestry) men have an intermediate incidence, and low incidences are reported for black and Asian men. It has been suggested that ethnic differences in incidence and mortality of PCa are related to genetic variations in genes that regulate androgen metabolism. We investigated the role of genetic variants in the androgen metabolism genes and the probability of developing PCa in South African coloured and white men. Methods. Genotype and allele counts and frequencies of single nucleotide polymorphisms (SNPs) in CYP3A5, CYP3A4 and CYP3A43 were assessed in coloured men (160 case individuals, 146 control individuals) and white men (121 case individuals, 141 control individuals). Results. A genetic association indicating an increased probability of developing PCa was observed with the G allele of the SNP rs2740574 in CYP3A4 in coloured men, the A allele of rs776746 (CYP3A5) and the G allele of rs2740574 (CYP3A4) in white men, and the G allele of rs2740574 and the C allele of rs501275 (CYP3A43) in the combined ethnic groups analysis. In addition, we identified allele combinations (termed haplotypes) with significantly higher frequencies in the PCa case individuals than in the control individuals. Conclusions. The findings support the role of variants in genes that regulate androgen metabolism and the probability of developing PCa. The study paves the way to identify other genetic associations in South African men, and to establish genetic profiles that could be used to determine disease progression and prognosis.     

Genetic polymorphisms in the cytochrome P450 1A1 and 2E1 genes, smoking, drinking and prostate cancer susceptibility: A case-control study in a Han nationality population in Southern China

AIM: To investigate the association among the polymorphisms of the cytochrome P450 1A1 and 2E1 genes, smoking, drinking and the risk of prostate cancer (PCa) in a Han nationality population in Southern China. METHODS: A case-control study including 225 PCa patients and 250 age-matched controls was conducted. The six polymorphic sites of the CYP 1A1 and CYP2E1 genes were analysed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) or allele-specific PCR technique using genomic DNA isolated from peripheral blood lymphocytes. RESULTS: We found that the CYP1A1 Val/Val genotype significantly increased the risk for PCa (OR, 2.26; 95% CI, 1.09-4.68). In contrast, the CYP2E1 C1/C2 (OR, 0.67; 95% CI, 0.46-0.99) or C2/C2 genotype (OR, 0.31; 95% CI, 0.10-1.00) significantly decreased the risk. Furthermore, the individuals carrying the CYP1A1 Val allele and the CYP2E1 C1/C1 genotype showed the highest risk (OR, 2.50; 95% CI, 1.45-4.29). Though there was no significant difference with smoking history (P = 0.237) or drinking habit (P = 0.499) between cases and controls, a deep smoking habit (OR, 2.02; 95% CI, 1.28-3.17) and heavy smoking history (OR, 1.61; 95% CI, 1.04-2.50) significantly increased the susceptibility of PCa after stratification by smoking method and accumulative smoking amount. Moreover, both the CYP1A1 Val allele (OR, 2.82; 95% CI, 1.49-5.35) and CYP2E1 C1/C1 genotype (OR, 2.57; 95% CI, 1.31-5.02) had obvious interaction with heavy smoking history that significantly raised the risk. We also discovered a significant interaction between the CYP2E1 C1/C1 genotype and drinking (OR, 1.85; 95% CI, 1.04-3.28). CONCLUSIONS: Individuals carrying the CYP1A1 Val allele or the CYP2E1 C1/C1 genotype with a smoking or drinking habit were at increased risk of PCa, which also showed a positive correlation with exposure dose of tobacco.     

8q24 rs1447295基因多态性与不同族群前列腺癌易感性的Meta分析

目的通过Meta分析系统评价8q24染色体rs1447295基因多态性与不同族群前列腺癌(prostate cancer,PCa)患病风险的相关性。方法检索万方、中国知网、PubMed、Science Direct、Web of Science、Wiley Online Library和中国生物医学文献数据库中涉及8q24 rs1447295基因多态性和PCa易感性的病例-对照研究。2位独立研究者按标准筛选文献,运用Cochrane工具及Stata 15.0软件行Meta分析,计算OR值、95%CI并进行偏倚风险评价。结果最终纳入相关文献36篇,涉及研究41项,包含25715例PCa患者和27018例健康对照者。结果显示,在5类基因模型中,等位基因模型、显性遗传模型、隐性遗传模型、纯合子遗传模型与杂合子基因模型显示8q24 rs1447295基因多态性均与PCa易感性之间存在显著相关性,差异有统计学意义(P<0.05)。进一步亚组分析显示,在高加索人种和亚洲人种中,8q24 rs1447295基因多态性与PCa易感性相关,且差异均有统计学意义(P<0.05),在非裔和拉美裔群体中未显示有统计学关联。结论8q24染色体rs1447295基因多态性与PCa患病风险有关,该相关性在高加索人种和亚洲人种中较为显著,在非裔和拉美裔群体关联性无显著差异。     

南京地区人群CYP2E1基因多态性及吸烟、饮酒与前列腺癌易感性

目的:探讨Ⅰ相代谢酶细胞色素P450 2E1(CYP2E1)基因RsaⅠ和PstⅠ位点多态性及吸烟、饮酒习惯与前列腺癌(PCa)发病风险的关系,并探讨基因与生活习惯在PCa发病中的联合作用。方法:采用PCR-RFLP技术检测109例原发性PCa患者及202例年龄匹配的男性非肿瘤患者外周血CYP2E1基因RsaⅠ和PstⅠ多态位点的基因型。结果:深吸烟(OR=2.29,95%CI:1.28～4.09)、重度吸烟史(OR=1.81,95%CI:1.02～3.22)等生活习惯为PCa易感因素。CYP2E1 C1/C1基因型与PCa易感性有显著相关(OR=1.71,95%CI:1.04～2.82),且与饮酒的联合作用明显与PCa易感性相关(OR=2.21,95%CI:1.06～4.59)。重度吸烟人群中,携带CYP2E1易感基因型(C1/C1)与不吸烟且携带非易感基因型(C1/C2或C2/C2)个体相比PCa的发病风险显著增高(OR=2.80,95%CI:1.20～6.56)。结论:携带CYP2E1易感基因型(C1/C1)并有烟酒嗜好者PCa的发病风险显著增高,且与烟草的暴露呈显著剂量反应关系。