CYP1A1 GSTM1基因多态性和吸烟与肺癌易感性关系的病例对照研究

目的:探讨天津市居民致癌物代谢酶CYP1A1和GSTM1基因多态性对肺癌易感性的影响。方法:利用限制性片断长度多态性-聚合酶链反应(RFLP-PCR)方法检测原发性肺癌患者和健康对照者细胞色素P450酶基因CYP1A1Msp位点和谷胱甘肽硫转移酶基因GSTM1的多态性情况。结果:肺癌组与对照组之间CYP1A1和GSTM1基因型分布差异均存在统计学显著意义(P<0.05)。携带CYP1A1变异基因型或GSTM1阴性基因型的个体患肺癌的危险性增高,比值比(OR)分别达到2.44(1.04～5.81)和1.84(1.03～3.29)。多因素分析结果显示具有CYP1A1变异基因型、GSTM1阴性基因型的吸烟个体患肺癌的风险较大。结论:CYP1A1Msp位点变异基因型和GSTM1阴性基因型可能是肺癌的易感因素,吸烟与肺癌易感基因之间具有协同作用。     

CYP1A1和GSTM1基因多态性与内蒙古人群肺癌易感性的关系

背景与目的 肺癌是严重危害人类健康的恶性肿瘤之一，其发病与肺癌人群中某些肺癌相关基因的遗传多态性有关。本研究旨在探讨细胞色素P4501A1（CYP1A1）基因多态性和谷胱甘肽硫转移酶M1（GSTM1）基因多态性与内蒙古人群肺癌易感性的关系。方法 用PCR-RFLP技术分析了原发性肺癌组和住院对照组（各163例）的CYP1A1、GSTM1基因的多态性、基因型分布频率和交互作用。结果 CYP1A1突变型和GSTM1基因缺陷型EGSTM1（-）]频率分布分别为36．8％、65．0％（病例组）和19．0％、48．9％（对照组），二者经χ^2检验差异有显著性（χ^2=12．82，P=0．000；χ^2=9．78，P=0．002）。CYP1A1突变型患肺癌的风险显著增加（OR=2．48，95％CI为1．51～4．08）。GSTM1（-）者患肺癌的风险也显著增加（OR=2．03，95％CI为1．30～3．17）。基因突变的协同分析发现CYP1A1突变型／GSTM1（-）在肺癌组和对照组中的分布频率分别为28．8％和8．0％，二者经χ^2检验有显著性差异（χ^2=23．883，P=0．000）。CYP1A1突变型／GSTM1（-）患肺癌的风险显著增加（OR=4．90，95％CI为2．50～9．83）。无论是在肺癌组还是在对照组，CYP1A1突变型／GSTM1（-）和CYP1A1非突变型／GSTM1（-）在性别间分布频率的差异均无显著性（肺癌组χ^2=0．797，P=0．372；对照组χ^2=0．670，P=0．761）。吸烟与肺癌易感性的统计学分析，结果显示吸烟与肺癌易感性有关（χ^2=14．197，P=0．000），吸烟者患肺癌的风险显著增加（OR=2．33，95％CI为1.50～3．62）。CYP1A1突变型与吸烟关系的协同分析发现，携带CYP1A1突变型基因的吸烟者较携带CYP1A1突变型基因不吸烟者易患肺癌（OR=4．44，95％CI为2．40～8．32，χ^2=23．843，P=0．000）。GSTM1（-）与吸烟关系的协同分析中也发现，携带GSTM1（-）的吸烟者患肺癌的风险显著增加（OR=7．32，95％CI为3．39～15．50，χ^2=36．708，P=0．000）。结论 CYP1A1突变型和GSTM1（-）是内蒙古地区肺癌的易患因素，二者对肺癌的发生有协同作用，吸烟与肺癌的易感性也有关，CYP1A1突变型、GSTM1（-）与吸烟在肺癌的发生上也有相互促进作用。     

CYP1A1、GSTM1基因多态性与肺癌易感性的研究

目的:探讨CYP1A1、GSTM1基因多态性与肺癌易感性之间的相关性。方法:利用RFLP-PCR(限制性片段长度多态性-聚合酶链反应)方法检测65例原发性肺癌和60例非肿瘤患者CYP1A1、GSTM1基因,再用NcoI及HinfI两种内切酶识别CYP1A1等位基因亚型。结果:1)肺癌组与对照组CYP1A1等位基因型Ile/Ile、Ile/Val、Val/Val的频率总体分布无显著性差异;但肺癌组CYP1A1(Val/Val)基因型频率(18.5%)明显高于对照组(8.3%),两组差异有显著性(P<0.05)。2)肺癌组GSTM1(-)基因型的频率(63.1%)明显高于对照组(45.0%),P<0.05。3)两种等位基因联合分析发现,与携带CYP1A1(Ile/Ile)/GSTM1(+)基因型的个体相比:CYP1A1(Ile/Ile)/GSTM1(-)以及CYP1A1(Ile/Val+Val/Val)/GSTM1(+)基因型个体患肺癌的风险度较高,OR分别为3.82(95.0%CI,1.27～11.45)和3.5(95.0%CI,1.18～10.41);而CYP1A1(Val/Val)/GSTM1(-)基因型个体患肺癌的风险度最高,OR为10.5(95.0%CI,1.70～64.73)。4)进一步分层分析发现,CYP1A1(Ile/Val+Val/Val)等位基因型主要增加鳞癌的危险性;而GSTM1基因型组织类型无明显的相关性。5)在分析吸烟对肺癌易感性的影响时发现,CYP1A1(Ile/Val+Val/Val)及GSTM1(-)等位基因型与吸烟有协同作用,并与至发病时的累积吸烟量有关。结论:CYP1A1(Val/Val     

细胞色素P4502E1基因多态与贲门癌易感性关系探讨

 目的　探讨细胞色素P4 5 0 2E1(CYP2E1)基因多态与贲门癌易感性的关系。方法　采用病例对照研究方法和聚合酶链反应 限制性片段长度多态性 (PCR RFLP)检测技术 ,对 15 9例贲门癌患者和 192例对照的CYP2E1基因多态性进行分析。结果　CYP2E13种基因型在贲门癌病例组和对照组的分布差异有显著性 (χ2 =16 .0 4 ,P <0 .0 1) ,比值OR为 2 .37(95 %CI :1.5 2～ 3.70 )。贲门癌病例组CYP2E1(c1/c1)基因型频率为 6 0 .4 % ,对照组为 4 0 .1%。吸烟且携带CYP2E1(c1/c1)基因型的个体与携带CYP2E1(c1/c2或c2 /c2 )基因型的不吸烟者相比 ,患贲门癌的OR为 4 .6 8(95 %CI:2 .19～ 10 .0 4 )。结论CYP2E1基因多态性与贲门癌易感性有关 ,与吸烟协同作用使贲门癌的危险显著增加     

细胞色素P450 2E1 RsaⅠ基因型、生活习惯因素及其相互作用与胃癌

[目的]研究CYP2E1 RsaⅠ基因型、生活习惯因素相互作用与胃癌易感性的关系。[方法]在消化道癌高发区淮安市进行了病例对照研究(胃癌145例，人群对照229例)，调查研究对象的烟酒茶嗜好及饮食习惯，以PCR，扩增、 RsaⅠ内切酶消化，分析研究对象的CYP2E1的基因型。[结果]胃癌组与对照组的CY：P2E1 RsaⅠc1／c2或c2／c2基因型频率无显著差异(41．4％：38．9％)。吸烟和常吃腌菜与CYP2E1c1／c2或c2／c2基因型在增加胃癌发生的危险性中有相乘效应。饮酒和不饮茶的习惯增加胃癌发生的危险性，但饮酒或不饮茶的这种作用不受CYP2E1基因型的影响。[结论]CYP2E1 RsaⅠ基因多态与吸烟及常吃腌菜之间的基因-环境交互作用影响个体对胃癌的易感性。     

细胞色素CYP2E1和GST M1与肺癌易感性的病例对照研究

目的探讨谷胱甘肽转硫酶(GST)和细胞色素CYP2E1多态性与肺癌易感性的关系.方法选取广州市广东籍新发肺癌病人91例及同期非肺部疾患及相同性别的病人91例作匹配,调查他们的吸烟、饮酒等因素的暴露情况.用聚合酶链式反应(PCR)和限制性片段长度多态性(RFLP)技术检测CYP2E1和GST的基因多态性.结果CYP2E1 C1C1基因型与C1C2基因型比较,其OR为1.82(95%CI=0.95～3.40),GSTM1基因缺失型的OR值为1.26(0.69～2.30),而两者联合分析时,则可增加患肺癌的危险,其OR值为2.13(0.82～5.56),但无统计学意义(P＞0.05).吸烟与肺癌关系密切,其OR值为2.82(1.56～5.12),当吸烟与这两种基因型协同作用时,可明显提高患肺癌的危险性,携带CYP2E1 C1C1基因型的吸烟者的OR值为5.42(2.05～14.32),GSTM1基因缺失型的吸烟者的OR值为4.38(1.81～10.61).多因素logistic回归分析结果表明:文化程度(OR为0.63,0.45～0.86)、吸烟量(OR为1.56,1.14～2.14)、元抽油烟机(OR为3.77,1.48～9.56)、食用动物油(OR为1.67,1.25～2.24)、胡萝卜(OR为0.47,0.22～0.98)、饮酒(OR为6.58,1.53～28.3)、直系亲属肺癌史(OR为3.75,1.64～8.58)等因素与肺癌有关,而上述两种基因均未进入模型.结论CYP2E1和GSTM1在单因素分析中未显示出与肺癌风险的联系.这两种基因分别与吸烟协同作用时明显提高肺癌的危险性.然而在多因素分析中均未进入logistic模型,说明它们均不是肺癌个体易感性的主效基因,而是次效基因.     

广州地区汉族人群肺癌易感性标记物CYP1A1、CYP2E1和GSTM1与肺癌关系的病例对照研究

[目的]探讨广州地区汉族人群谷胱苷肽硫转移酶（GSTM1）、细胞色素P4501A1（CYP1A1）和细胞色素P4502E1（CYP2E1）基因多态性与肺癌易感性的关系。[方法]选取中山大学附属第一医院、广州市肿瘤医院、广州市红十字会医院等医院的广州籍新发肺癌病人91例及同期上述各医院的同性别非肺部疾患病人91例作对照，采用聚合酶链式反应（PCR）和限制性片段长度多态性（RFLP）技术检测CYP1A1、CYP2E1和GSTM1的基因多态性。[结果]与野生型的CYP1A1相比，突变型肺癌OR为1．51（0．76～3．011。CYP2E1C2C2基因型与C1C1基因型比较，其OR为5．48（1．21～25．23）．GSTM1基因缺失型的OR值为1．26（0．69～2.30）．而三者联合作用时．则可增加患肺癌的危险，其OR值为3．97（0．94-16．791，但无统计学意义（P〉0．05）。[结论]CYP1A1、CYP2E1和GSTM1的某些基因型增加了患肺癌的危险性，但尚未达到统计学的显著性水平，说明它们均不是肺癌个体易感性的主效基因．而是次效基因。     

代谢酶基因多态性与肺癌易感性关系的研究

目的　探讨代谢活化酶细胞色素P45 0 1A1(CYP1A1)、2D6(CYP2D6)、2E1(CYP2E1)和代谢解毒酶谷胱甘肽硫转移酶 (GSTM 1)基因多态性与肺癌易感性的关系及重度吸烟对肺癌易感性的影响。方法　采用PCR、PCR RFLP等技术检测 180例原发性肺癌患者及 2 2 4例肺部良性疾病患者和正常人 (对照组 )外周血代谢酶基因型。结果　CYP1A1突变等位基因 (m )、CYP2D6野生型等位基因 (w )、CYP2E1A基因型和GSTM 1功能缺失型 ( -)可使患肺癌的危险性增加到 1.5 0～ 1.5 8倍 (P <0 .0 5 )。携带GSTM 1( -)者若同时携带CYP1A1、2D6或 2E1中任意 1个易感基因型 ,可使患肺癌的危险性升高到 2 .2 4～ 2 .69倍 (P <0 .0 5 )。携带相同基因型者 ,重度吸烟比不吸烟者患肺癌的危险性显著升高。重度吸烟人群中携带 4种易感基因型者患肺癌的危险性显著增高 ,达 9.85倍 ( 95 %CI =2 .3 0～ 45 .71)。结论　代谢酶基因的易感等位基因携带者患肺癌的危险性上升 ,且与烟草致癌物暴露剂量呈正相关。     

细胞色素P450 2E1基因多态性与食管癌易感性关系的Meta分析

目的探讨细胞色素P450 2E1（CYP2E1）基因多态性与食管癌易感性的关系。方法检索CBMdisc、CMCC、CNKI、Medline、Pubmed等数据库,并收集未公开发表的文章及硕、博士学位论文,获得有关CYP2E1基因多态性与食管癌易感性的关系的文献进行Meta分析,以病例组及对照组CYP2E1基因型分布的比值比（OR值）为效应指标,确定纳入标准,对文献进行筛选,异质性检验,然后应用Meta分析软件RevMan4．2．2对各研究原始数据进行统计处理,计算合并OR值及95％可信区间。结果按照纳入标准,最终进入系统评价的文献共有11篇病例对照研究,其中食管癌患者1094例,对照1329例,Meta分析结果合并OR=2．61,95％可信区间为1．68—4．05,说明CYP2E1基因型频率分布与食管癌的关联有统计学意义。结论对目前相关研究结果的Meta分析显示,CYP2E1基因多态性与食管癌易感性之间存在相关,即携带Rsa Ⅰ／PstⅠ识别的野生型CYP2E1基因纯合子的个体发生食管癌的危险性较高。     

CYP1A1多态性与肺癌遗传易感性的关系

目的探讨代谢酶基因CYP1A1基因多态性与中国汉族人群肺癌遗传易感性之间的相关性。方法应用AS-PCR技术检测150例中国四川汉族肺癌和152例中国四川汉族健康人的CYP1A1基因Exon7多态性分布频率,并分析了Exon7多态性与中国四川汉族人群肺癌遗传易感性之间的相关性。结果CYP1A1Exon73种多态基因型分布频率在两组间比较差异无统计学意义,χ2=0.634,P=0.728。携带突变Val基因型的个体较携带Ile/Ile基因型的个体患肺癌的危险性增加,OR=1.139,95%CI为0.635~2.042,P=0.662。携带突变Val基因型的个体较携带Ile/Ile基因型的个体患肺鳞癌的风险显著增加,OR=3.510,95%CI=1.326~9.293,P=0.011。结论Val突变等位基因可能是中国四川汉族人群的肺癌易感基因。CYP1A1基因Exon7多态性在肺鳞癌发生中起重要作用。     

DNA切除修复交叉互补基因1、乳腺癌易感基因、核苷酸还原酶1与非小细胞肺癌

 阐述了近年来非小细胞肺癌（NSCLC）化疗敏感性与DNA 切除修复交叉互补基因1 （ERCC1）、乳腺癌易感基因（BRCA1）、核苷酸还原酶1（RRM1）基因表达关系的研究进展，分析3个基因对NSCLC个体化化疗潜在的指导意义     

CYP1A1、GSTM1基因多态性及其联合作用与食管癌的易感性

目的探讨CYP1A1、GSTM1基因多态性及其联合作用与新疆汉族人食管癌易感性的关系。方法采用聚合酶链式反应-连接酶检测反应分析方法检测107例食管癌患者和204例非食管癌患者的CYP1A1(rs1048943、rs4646421和rs4646903)和GSTM1(缺失型和rs2071487)的基因型。结果CYP1A1基因rs1048943位点的等位基因和基因型频率在病例组和对照组之间比较,总体分布差异有统计学意义(χ² =5.52,P=0.019)。与A/A基因型相比,GG+AG基因型可增加食管癌的发病风险(OR=1.79,OR95%CI:1.10~2.92);GSTM1基因缺失型和非缺失型在病例组和对照组中的分布频率分别为68.69%、31.31%和48.39%、51.61%,在两组间的分布差异有统计学意义(χ²=10.55,P=0.001;OR=2.34,OR95%CI:1.40~3.91)。结论CYP1A1基因rs1048943位点多态性和GSTM1基因缺失型与新疆地区汉族人食管癌易感性有相关性。     

VEGFR1和MDR1在胃癌中的表达及意义

目的:探讨VEGFR1和MDR1在胃癌中的表达及意义.方法:采用免疫组化SP法检测VEGFR1和MDR1在胃癌中的表达及与分化程度的关系;比较VEGFR1和MDR1在胃癌中的表达相关性.结果:VEGFR1在高、中、低度分化胃癌的表达率依次为15/53(28%)、19/43(44%)、37/54(68%); 在低分化胃癌组织中的表达明显高于高分化和中分化胃癌组织(P＜0.05).MDR1在高、中、低度分化胃癌的表达率依次为18/53(34%)、21/43(48%)、41/54(76%); 在低分化胃癌组织中的表达明显高于高分化和中分化胃癌组织 (P＜0.05).结论:VEGFR1和MDR1在胃癌中的表达具有一致性,可能在胃癌的多药耐药中扮演重要角色.     

RB1CC1 activates the promoter and expression of RB1 in human cancer

RB1‐inducible coiled‐coil 1 (RB1CC1, also known as FIP200) is a tumor suppressor implicated in the regulation of RB1 (retinoblastoma 1) expression. However, the molecular mechanism of RB1 regulation by RB1CC1 has not been elucidated. Here, we demonstrate that nuclear RB1CC1 binds to the RB1 promoter using chromatin immunoprecipitation assays with anti‐RB1CC1 antibody. Luciferase assays with RB1 promoter reporter plasmids revealed that RB1CC1 activated the RB1 promoter through the 201 bp upstream GC‐rich region (from the initiation ATG). Electrophoretic mobility shift assay and Western blot analysis supported RB1CC1 binding to the GC‐rich region of the RB1 promoter. In addition, the C‐terminus of RB1CC1 was required for nuclear localization and subsequent RB1 promoter activation. Furthermore, the expression levels of RB1CC1 and RB1 significantly correlated with in vivo breast cancer tissues as determined by immunohistochemical analysis. These data indicate that nuclear RB1CC1 directly activates the RB1 promoter to enhance RB1 expression in cancer cells. Evaluation of RB1CC1 in various types of human cancer tissues is expected to provide useful information for clinical practice and future therapeutic strategies. © 2009 UICC     

Polymorphisms of CYP1A1, GSTM1, GSTT1, and prostate cancer risk in Turkish population

Prostate cancer is the most common cancer among men in many countries. Although the etiology of prostate cancer largely is unknown, both genetic and environmental factors may be involved. Advanced age, androgen metabolism, and heredity-race have been reported to be possible risk factors. On the other hand, several studies indicate that genetic polymorphisms in biotransformation enzymes play a role in prostate cancer development. In this study, association of the prostate cancer risk with genotype frequencies of the Phase I (CYP1A1) and Phase II (GSTM1 and GSTT1) biotransformation enzymes was investigated in 321 Turkish individuals (152 prostate cancer patients and 169 age-matched male controls). The presence or absences of the GSTM1 and GSTT1 genes were determined by a PCR-based method. Genotypes of CYP1A1 were determined by MspI-RFLP. The prevalence of GSTM1 null genotype in the cases was 64 percent, compared to 31 percent in the control group, indicating a strong association (OR = 4.08, 95%CI = 2.50-6.69). No association was observed between either GSTT1 null genotype or CYP1A1 polymorphism and prostate cancer incidence. No statistically significant association was observed between smoking status of the patients and any of the polymorphisms studied. In conclusion, results of this study indicate that only the GSTM1 null genotype may play an important role as a risk factor for prostate cancer development in Turkish population.     

Genetic Variation of GSTM1, GSTT1 and GSTP1 Genes in a South Indian Population

The glutathione S transferase (GST) family of enzymes play a vital role in the phase II biotransformation ofenvironmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic and the polymorphismsin GST genes have been associated with cancer susceptibility and prognosis. Moreover, distinct ethnic differenceshave been observed in the type and frequency of GST gene polymorphisms. Hence, the present study was aimed todetermine the frequencies of GSTM1, GSTT1 and GSTP1 polymorphisms in 255 healthy random volunteers fromSouth India. The GSTM1 and GSTT1 genotypes were determined by PCR and GSTP1 by PCR-RFLP using peripheralblood DNA.The GSTM1 and GSTT1 null genotype frequencies were found to be 22.4% and 17.6% respectively. TheGSTP1 allelic frequency was 0.78 for the Ile allele and 0.22 for the Val allele and the genotype frequency was 58.4%for Ile/Ile, 38.4% for Ile/Val, and 3.1% for Val/Val. Comparison of the frequencies of GST polymorphisms observedin the present study with other Indian and world populations revealed a distinctive nature of the South Indianpopulation with respect to polymorphims at the GST gene loci. A better understanding of carcinogen metabolizinggene distribution should contribute to risk assessment of humans exposed to environmental carcinogens.     

hSav1蛋白高表达对Mst1介导的细胞凋亡的影响

目的 观察hSav1蛋白高表达对Mst1介导的细胞凋亡的影响,探讨hSav1在Mst1介导的细胞凋亡中的作用.方法 构建蛋白hSav1的载体pCMV-HA-hSav1与蛋白Mst1的载体pcDNA/4TO-Flag-Mst1,共转染HeLa细胞.采用相应抗体做二者的免疫共沉淀,以证实蛋白hSav1和Mst1之间的相互作用;应用细胞免疫荧光共定位,进一步证实二者之间的相互作用.在HeLa细胞中,分别单独或同时转染质粒pcDNA/4TO-Flag-Mstl和pCMV-HA-hSav1,转染36 h后,加入凋亡诱导剂顺铂(50 μmol/L)作用14 h.应用磷脂结合蛋白碘化丙啶(Annexin V/PI)法检测细胞凋亡,观察蛋白hSav1高表达对Mst1介导的细胞凋亡的影响.结果 载体pCMV-HA-hSav1与pcDNA/4TO-Flag-Mst1构建成功,测序结果表明无突变或缺失.免疫共沉淀结果显示,蛋白hSav1可以在Mst1抗体的免疫沉淀物中检测出来,蛋白Mst1可以在hSav1抗体的免疫沉淀物中检测出来.细胞免疫荧光的结果显示,二者的荧光在细胞内存在共定位,并可充分融合.HeLa细胞中,单独Mst1蛋白高表达组的细胞凋亡率为24.5%±2.4%,单独hSav1蛋白高表达组与对照组比较,无明显细胞凋亡.蛋白Mst1和hSav1高表达组的细胞凋亡率为39.3%±4.0%,差异有统计学意义(P<0.05).结论 蛋白hSav1与Mst1在HeLa细胞内存在相互作用,蛋白hSav1高表达可明显促进由蛋白Mst1介导的细胞凋亡.     

CYP1A1, GSTM1, GSTT1 and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians

The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.