原发性肺癌GSTM1基因多态性与化疗效果关系的研究

背景与目的GSTM1参与环境污染物如苯丙芘和其它多环芳烃及抗癌药等的代谢,其多态性是否会影响肺癌患者的化疗效果及预后,国内相关研究比较少,本研究旨在揭示GSTM1多态性是否与化学药物治疗的敏感性有关以及对患者预后的影响。方法采用聚合酶链反应技术,检测接受化学药物治疗的137例原发性肺癌患者GSTM1基因型频率分布情况。结果137例肺癌患者GSTM1缺陷型频率为58.4%（80/ 137）,功能型频率为41.6%（57/137）;化疗有效组GSTM1缺陷型频率为69.05%（58/84）,化疗无效组GSTM1缺陷型频率为41.51%（22/53）,二者有统计学差异（P=0.001）。采用铂类化疗方案的患者,化疗有效组GSTM1缺陷型频率为65.43%（53/81）,化疗无效组GSTM1缺陷型频率为42%（21/50）,二者有统计学差异（P= 0.0025）。对于进展期患者化疗有效组GSTM1缺陷型频率为70.13%（54/77）,化疗无效组GSTM1缺陷型频率为41.51%（22/53）,二者有统计学差异（P=0.001）。当化疗有效时携带GSTM1功能型的鳞癌、小细胞癌患者生存时间（中位生存期分别为42个月和14个月）比携带GSTM1缺陷型的鳞癌、小细胞癌患者长（中位生存期分别为6个月和7个月）（P〈0.05）;而腺癌患者,携带GSTM1功能型和缺陷型的生存时间（中位生存期分别为13个月和11个月）差异无统计学意义（P〉0.05）。对于化疗无效的患者,不论GSTM1为何种基因型、病理分型如何,患者中位生存期均比较接近,生存时间没有统计学差异（P〉0.05）。结论GSTM1缺陷型的患者接受化学药物治疗的效果比GSTM1功能型的患者好;采用铂类化疗方案时GSTM1缺陷型的患者化疗效果比GSTM1功能型的患者好。当化疗有效时,患者生存时间与病理分型、GSTM1基因型相关。     

Ⅰ、Ⅱ相药物代谢酶遗传多态性与晚期非小细胞肺癌化疗疗效的关系

背景与目的目前药物代谢酶遗传多态性与化疗疗效关系的研究结果多不一致,本研究旨在探讨细胞色素P4501A1(cytochrome P450 1A1,CYP1A1)、2E1(cytochrome P450 2E1,CYP2E1)、2D6(cytochrome P450 2D6,CYP2D6)和谷胱甘肽硫转移酶M1(glutathione S-transferase M1,GSTM1)基因多态性与晚期非小细胞肺癌化疗疗效以及与肺癌患者预后的关系。方法采用PCR和PCR-RFLP技术对肺癌患者4种药物代谢酶基因分型,并对他们进行5年跟踪随访。结果携带B型CYP1A1和缺陷性GSTM1肺癌患者比其它基因型患者化疗疗效好(P<0.001)。携带A型CYP1A1肺癌患者接受非铂类化疗药物治疗比B型和C型患者疗效好(P=0.041);携带缺陷性GSTM1肺癌患者接受铂类化疗药物治疗疗效比功能型患者疗效好(P=0.011)。4种酶对晚期非小细胞肺癌患者总生存期(overall survival,OS)没有明显影响(P>0.05)。结论 A型CYP1A1肺癌患者接受非铂类化疗药物治疗比B型和C型患者疗效好;缺陷性GSTM1肺癌患...     

肺癌患者GSTM1基因型与p53基因突变的相关关系研究

目的:探索肺癌患者Ⅱ相代谢酶主要亚型GSTM1的基因型与p53基因突变的关系.方法:应用双重PCR和PCR-SSCP(单链构像多态性分析)技术,检测了63例肺癌患者和47例健康对照中GSTM1基因缺失及肺癌组织p53基因突变的情况,并分析其相关关系.结果:肺癌组GSTM1基因缺失率为71.4%(45/63),对照组为51.1%(24/47),差异有显著统计学意义,OR为2.40(95%CI为1.09-5.29).p53基因突变率在63例肺癌组织中为49.2%(31/63),在15例对照组织中仅为6.6%(1/18).58.1%肺癌病例同时存在p53基因突变和缺失GSTM1基因(P＜0.05).结论:GSTM1基因缺失与p53基因突变相关,GSTM1基因缺失可能增加p53基因突变的几率,从而导致肺癌患病危险性的增加.     

ERCC1 codon118单核苷酸多态性与非小细胞肺癌铂类化疗的临床预后研究

目的:探讨肿瘤石蜡组织中ERCC1 codon118单核苷酸多态性(single nucleotide polymorphism,SNP)与接受铂类药物化疗非小细胞肺癌(chemotherapy;non-small-cell lung cancer,NSCLC)患者临床预后之间的关系。方法:采用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)的方法评价47例石蜡包埋NSCLC肿瘤组织中DNA修复基因ERCC1第118位密码子的单核苷酸多态性,并比较不同基因型与NSCLC组织临床病理及铂类化疗预后之间的关系。结果:所有NSCLC患者中位生存时间为16.0月(95%CI,16.4-28.4月),中位无进展生存期为8.0月(95%CI,9.4-16.9月)。ERCC1 codon118与NSCLC临床病理特征均未见相关性。携带ERCC1 C/C基因型的NSCLC患者的中位总生存时间为25.0月,而携带C/T及T/T基因型患者的中位总生存时间仅为10.5月,两者有统计学差异(P=0.012)。携带ERCC1 C/C基因型的NSCLC患者的中位无进展生存期为13.2月,而携带C/T及T/T基因型患者的中位无进展生存期仅为6.0月,两者有统计学差异(P=0.029)。结论:ERCC1 codon118基因单核苷酸多态性与接受铂类药物化疗的NSCLC患者的总生存时间和无进展生存期有关,在一定程度上可以作为判断NSCLC患者铂类药物化疗的预后指标。     

ERCC1在晚期非小细胞肺癌中的表达及临床意义

目的:探讨核苷酸切除修复交叉互补基因1(ERCC1)在晚期非小细胞肺癌中的表达及其临床意义.方法:采用免疫组化S-P法检测78例Ⅲ期、Ⅳ期非小细胞肺癌患者中核苷酸切除修复交叉互补基因1(ERCC1)的表达情况.所有患者均以铂类为基础的化疗方案化疗.将患者化疗疗效和生存资料与ERCC1的表达进行比较.结果:78例患者ERCC1的阳性表达率为47.44%(37/78),ERCC1表达与患者性别、年龄、病理类型(鳞癌、腺癌)及临床分期无关;ERCC1阴性组化疗临床受益率是73.17%(30/41),ERCC1阳性组为51.35%(19/37),两组比较差异有统计学意义(χ2=3.9643,P=0.0465).ERCC1阳性组生存期为(21.1852±22.1134)月,ERCC1阴性组生存期为(12.375±10.0827)月,两组比较差异无统计学意义(P=0.0879).结论:ERCC1的表达与晚期非小细胞肺癌患者铂类药物化疗临床受益相关,检测ERCC1的表达对化疗药物的选择有一定指导意义.     

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     

应用SYBR green Ⅰ荧光PCR研究GSTM1基因多态性与肺癌遗传易感性之间的相关性

背景与目的谷胱甘肽S转移酶M1(glutathione S-transferase M1,GSTM1)基因是参与体内多种致癌物代谢的重要的II相代谢酶,其基因多态性被认为与人肺癌遗传易感性有关。本研究旨在探讨天津地区汉族人群GSTM1基因多态性与肺癌遗传易感性之间的关系。方法采用SYBR green I实时荧光PCR熔解曲线分析方法检测天津地区265例肺癌患者和307例对照者GSTM1基因多态性,应用病例对照研究分析其与肺癌易感性及不同病理类型之间的关系。结果①GSTM1(-)基因型在肺癌组和对照组的分布频率分别为56.6%和57.0%,两组之间无统计学差别(χ2=0.831,P=0.362)。经性别、年龄、吸烟状况调整后分析,携带GSTM1(-)基因型个体未增加患肺癌危险性(OR=0.840,95%CI:0.578-1.221,P=0.362)。②按病理分层分析GSTM1基因型与肺癌各病理类型之间的关系,其中鳞癌、腺癌、小细胞肺癌与其它病理类型肺癌患者GSTM1(-)基因型分布频率分别为65.8%、48.5%、47.8%和52.2%,与对照组相比,不同病理类型患者肺癌危险性均无明显统计学差异(P0.05)。结论在天津地区人群中GSTM1基因多态性与肺癌遗传易感性之间无相关性。     

ERCC1基因多态性与晚期非小细胞肺癌患者铂类化疗疗效的关系

背景与目的有关ERCC1基因多态性是否影响接受含铂化疗的晚期非小细胞肺癌患者疗效及生存的研究结果不相一致。本研究前瞻性研究90例接受含铂方案化疗的初治晚期非小细胞肺癌患者ERCC1基因C8092A和第118位密码子多态性与疗效的关系。方法全部患者均接受含铂联合方案化疗,采用测序法对患者基因型进行分型,比较不同基因型与疗效的关系。结果ERCC1C8092A基因型频率分别为CC40.0%(36/90)、CA48.9%(44/90)、AA11.1%(10/90),第118密码子基因型频率分别为CC58.9%(53/90)、CT34.4%(31/90)、TT6.7%(6/90)。C8092ACC基因型有效率与CA、AA基因型无统计学差异(33.3%vs29.6%,P=0.71),ERCC1118CC基因型患者有效率与CT和TT基因型无统计学差异(32.1%vs24.3%,P=0.43)。C8092ACC基因型患者与CA和AA基因型PFS无统计学差异(5.2个月vs5.4个月,P=0.62),ERCC1118CC基因型患者CT和TT基因型PFS无统计学差异(5.5个月vs5.3个月,P=0.59)。结论ERCC1C80...     

GSTM1、GSTT1基因多态性与四川北部地区肺癌易感性关系的研究

目的:探讨谷胱苷肽硫转移酶M1(GSTM1)和T1(GSTT1)基因多态性与四川北部地区汉族人群肺癌易感性的关系。方法:采用病例对照研究和聚合酶链式反应(PCR)技术检测四川北部地区肺癌病人125例和健康对照组125例中GSTM1(-)和GSTT1(-)的频率,评价两基因型及两基因的交互作用与肺癌易感性的关系。结果:GSTM1(-)在肺癌组和对照组分布频率分别为58.4%和56.8%,单因素回归分析未见统计学差异(OR=1.06,95%CI:0.639-1.757,P=0.822);GSTT1(-)在肺癌组和对照组分布频率分别为45.6%和44.8%,单因素回归分析未见统计学差异(OR=0.968,95%CI:0.588-1.593,P=0.899),GSTM1(-)和GSTT1(-)联合并未增加肺癌风险(OR=1.084,95%CI:0.536-2.192,P=0.823)。结论:GSTM1及GSTT1各基因型单独或联合作用都不是四川北部地区汉族人群肺癌的风险因素。     

GSTP1、XPG基因多态性与晚期非小细胞肺癌患者铂类药物化疗疗效及生存期的关系

背景与目的:本文旨在探讨谷胱甘肽S转移酶P1(glutathione S-transferase P1,GSTP1)基因A105G和人着色性干皮病G组(xeroderma pigmentatosum group G,XPG)基因C46T多态性与晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者对以铂类药物为主方案的化疗疗效及生存期的关系。方法:经病理学确诊的晚期NSCLC患者85例,化疗前取静脉血采用DNA测序法检测GSTP1 A105G和XPG C46T多态性,给予以铂类药物为主方案的化疗,2个周期后进行临床疗效评价(RECIST标准)并统计疾病进展时间(time to progression,TTP)和总生存时间(overall survival,OS),分析GSTP1 A105G和XPG C46T多态性与化疗疗效及生存期的关系。结果:85例晚期NSCLC患者中,GSTP1 A/G+G/G基因型和A/A基因型患者化疗有效率分别为43.59%和19.57%,差异有统计学意义(χ2=5.738,P<0.05);XPG C/C基因型和C/T+T/T基因型患者化疗有效率分别为42.86%和18.60%,差异有统计学意义(χ2=5.886,P<0.05);联合多态性分析显示,同时携带GSTP1 A/G+G/G和XPG C/C基因型患者化疗有效率最高为44.74%,组间比较差异有统计学意义(P<0.05)。至随访结束,81例患者中位TTP为6.5个月,其中GSTP1 A/G+G/G基因型为8.0个月,A/A基因型为6.0个月,差异有显著统计学意义(χ2=14.688,P<0.01);XPG C/C基因型为7.5个月,C/T+T/T基因型为6.0个月,差异有显著统计学意义(χ2=10.897,P<0.01);联合多态性分析显示,同时携带GSTP1 A/G+G/G和XPG C/C基因型患者的中位TTP最长为8.0个月,组间比较差异有显著统计学意义(P<0.01)。78例患者中位OS为9.0个月,其中GSTP1 A/G+G/G基因型为11.0个月,A/A基因型为9.0个月,差异有显著统计学意义(χ2=14.522,P<0.01);XPG C/C基因型为10.5个月,C/T+T/T基因型为9.0个月,差异有显著统计学意义(χ2=12.136,P<0.01);联合多态性分析显示,同时携带GSTP1 A/G+G/G和XPG C/C基因型患者的中位OS最长为11.0个月,组间比较差异有显著统计学意义(P<0.01)。结论:GSTP1 A105G和XPG C46T多态性可单独及联合用于预测晚期NSCLC患者对以铂类药物为主方案的化疗疗效及生存期,初步提示可以根据患者基因型来指导个体化治疗。     

Predictive Role of Glutathione-S-transferase Gene Polymorphisms in Risk and Prognosis of Hepatocellular Carcinoma

Aim: We conducted a prospective study in an Chinese population to detect associations of GSTM, GSTT andGSTP polymorphisms with hepatocellular carcinoma (HCC), and analyze roles in determining survival outcome.Methods: A prospective follow-up study was conducted with 476 HCC patients and 481 controls collected fromMay 2005 to May 2007. All patients were followed up until the end of Dec. 2011. GSTM1, GSTT1 and GSTP1genotyping were performed by PCR-CTPP methods. Results: Null GSTM1 carriers had a 1.64 fold risk of HCCcompared with non-null genotype, while GSTP1 Val/Val carriers had a 93% increased risk over the GSTP1IIe/IIe genotype. The median follow-up time for the 476 patients was 34.2 months (range: 1 to 78 months).Individuals with null GSTM1 genotype had better survival of HCC than non-null genotype carriers ( HR=0.71,95%CI=0.45-0.95). Similarly, GSTP1 Val/Val genotypes had significant better survival than the GSTP1 IIe/IIegenotype (HR=0.34, 95%CI=0.18-0.65). Individuals carrying null GSTM1 and GSTP1 Val/Val who receivedchemotherapy had lower risk of death from HCC than those without chemotherapy. Conclusion: This studyindicated carriage of null GSTM1 and GSTP1 Val/Val genotypes to have roles in susceptibility to and survivalfrom HCC.     

Predictive Role of GSTs on the Prognosis of Breast Cancer Patients with Neoadjuvant Chemotherapy

Objective: To evaluate the predictive value of GST gene polymorphisms with regard to prognosis of breastcancer patients receiving neoadjuvant chemotherapy. Methods: A total of 159 patients were included in our studybetween January 2005 and January 2007. All the patients were followed up until January 2012. Genotypingwas based upon the duplex polymerase-chain-reaction with the PCR-CTPP method. Results: Patients withnull GSTM1 and GSTP1 Val/Val genotypes had significantly had better response rates to chemotherapy whencompared with non-null GSTM1 and GSTP1 Ile/ Ile genotypes (OR=1.96 and OR=2.14, respectively). Patientswith the GSTM1 null genotype had a longer average survival time and significantly lower risk of death thandid those with non-null genotypes (HR=0.66). Similarly, those carrying the GSTP1 Val/Val genotype had 0.54-fold the risk of death of those with GSTP1 Ile/ Ile (HR=0.54). Conclusion: A significant association was foundbetween GSTM1 and GSTP1 gene polymorphisms and clinical outcomes in breast cancer cases.     

Glutathione S-transferase M1, T1, and P1 polymorphisms and survival among lung cancer patients.

Glutathione S-transferase (GST) enzymes detoxify therapeutic drugs and reactive oxidants, so GST polymorphisms may influence survival after diagnosis of cancer. We evaluated survival according to GST polymorphisms in a population-based series of lung cancer patients. The study subjects (n = 274) were men diagnosed with lung cancer from 1993 through 1996 who participated in a case control study and provided a blood sample for genotyping. The presence of the GSTM1 and GSTT1 genes were assayed by multiplex PCR. Genotype at the GSTP1 Ile(105)Val substitution was determined by PCR and oligonucleotide ligation assay. The study subjects were followed for vital status through 2000, and overall survival was evaluated in Kaplan-Meier survival functions and Cox proportional hazards models. Subjects with the GSTM1 null genotype had shorter survival; the proportion of GSTM1 null subjects surviving at 5 years was 0.20 [95% confidence interval (CI) 0.14-0.27], compared with 0.29 (95% CI 0.22-0.37) for GSTM1 present subjects. The relative risk of death associated with GSTM1 null genotype, adjusted for stage at diagnosis and histology, was 1.36, 95% CI 1.04-1.80. There was no association between GSTT1 or GSTP1 genotype and survival in the overall study population, nor in a subgroup of patients treated with chemotherapy (n = 130). For GSTM1, our results are consistent with a previous study, which also observed that the GSTM1-null genotype, which confers susceptibility to lung cancer, was associated with shorter survival. Future studies of lung cancer survival should take into account GSTM1 genotype as well as investigate underlying mechanisms.     

谷胱甘肽转移酶T1和M1基因多态性及吸烟与结直肠癌关系的对照研究

目的　研究谷胱甘肽转移酶 (GSTs)M1、T1基因多态性与结直肠癌易感性的关系。方法12 6例结直肠癌患者和 343例随机抽样的正常对照者 ,应用多重聚合酶链反应 (PCR)方法检测其GSTM1和GSTT1基因多态性 ,采用非条件Logistic回归模型分析基因型、吸烟情况与结直肠癌患病的关系。结果　GSTM1和GSTT1缺陷型基因型在对照人群中的频率分布为 5 5 .5 %和 2 0 .4 %。在GSTT1缺陷型基因型的人群中 ,GSTM1缺陷型患直肠癌风险是非缺陷型者的 9.74倍 (95 %CI为 1.13～83.85 )。现在吸烟者中 ,GSTM1缺陷型基因型患结肠癌的风险是非缺陷型者的 2 .2 2倍 (P >0 .0 5 ) ;GSTT1缺陷型基因型患结肠癌的风险是非缺陷型者的 4 .5 5倍 (95 %CI为 1.14～ 18.17) ,患直肠癌的风险是非缺陷型者的 4 .6 0倍 (95 %CI为 1.11～ 19.11)。结论　GSTM1和GSTT1缺陷型基因型有可能增加结直肠癌的危险性 ,其危险性主要表现在两者的联合作用上 ;环境暴露因素———吸烟和相关代谢酶多态性也表现出增加结直肠癌危险性的联合作用。     

Platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma: glutathione S-transferase genetic polymorphisms as predictive biomarkers of disease outcome

Background. The glutathione S-transferases (GSTs) are a group of multifunctional enzymes that catalyze the conjugation of glutathione with a variety of electrophilic compounds, including cytotoxic agents. A significant percentage of normal individuals exhibit genetic polymorphism with a homozygous deletion (null genotype) of the genes, leading to absence of the enzyme.Methods. In the present study we analyzed GSTM1 and GSTT1 polymorphisms in the genomic DNA isolated from peripheral blood of patients with ovarian cancer treated with chemotherapy (paclitaxel and cisplatinum) after cytoreductive surgery and assessed its correlation with the clinical outcome of these patients. The median follow-up for the patients was 30 months.Results. The estimated 3-year survival rate was 59.8% for all patients and 20.8% for carriers of GSTM1-wt/GSTT1-wt (wt indicates wild type) genotype combination (37.7% for GSTM1-wt alone) compared with 83.1% for non-GSTM1-wt/GSTT1-wt genotype carriers (100% for GSTM1-null). The mean survival time was significantly better in patients who are carriers of the GSTM1-null genotype (40.5 vs. 33.5; P = 0.006) or carriers of non-GSTM1-wt/GSTT1-wt genotypes (55.4 vs. 30.7; P = 0.009). The progression-free interval was more favorable for GSTM1-null carriers (41.9 vs. 27.4; P = 0.024).Conclusion. The study suggests that characterization of the drug-metabolizing genetic individual profile can be of great interest in clinical oncology. It can define the optimal chemotherapy for each patient, improve the efficiency, and reduce the incidence of drug toxicity and poor drug responses.     

Predictive potential of glutathione S-transferase polymorphisms for prognosis of osteosarcoma patients on chemotherapy

Objective: To evaluate the predictive value of glutathione S-transferase (GST) gene polymorphisms for theprognosis of osteosarcoma patients receiving chemotherapy. Methods: A total of 159 patients were included inour study between January 2005 and December 2007., with follow-up until January 2012. Genotyping was basedupon the duplex polymerase-chain-reaction with the PCR-CTPP method. Results: At the time of diagnosis, 15.4%of the patients presented with metastasis, while 22.3% developed metastasis during follow-up. At the time of finalanalysis on January 2012, the median follow-up was 45.5 months. Patients with null GSTM1 and GSTT1 hada higher event free survival rate than non-null genotype, but no significant association was found between thetwo genotypes and prognosis of osteosarcoma. Individuals with GSTP1 Val/Val genotype tended to live shorterthan with the IIe/IIe genotype, and we found a significantly higher risk of death from osteosarcoma (adjustedHR=2.35, 95% CI=1.13-4.85). Conclusion: The GSTP1 gene polymorphism may have an important role in theprognosis of osteosarcoma patients with chemotherapy. Further analyses with larger samples and more genesencoding metabolizing and DNA repair enzymes are warranted.     

The association between polymorphisms in glutathione S-transferase (GSTM1 and GSTT1) and lung cancer outcome

BACKGROUND: Polymorphisms in the glutathione S-transferase (GST) family may be associated with increased risk of lung cancer, somatic changes in lung tumour tissue, and survival. We evaluated survival according to GST polymorphism in lung cancer patients. METHODS: We studied DNA polymorphisms of 81 primary lung cancer patients at 2 glutathione-related loci: GSTM1, and GSTT1 that encode glutathione S-transferase-mu, and glutathione S-transferase- square. The presences of the GSTM1 and GSTT1 genes were assayed by PCR. Kaplan-Meier with log rank tests, and Cox regression models were applied in the analysis. RESULTS: The median age of 75 males and 6 females was 60 years. Median survival of the whole population was 8 months. In the first presentation, none of the patients with GSTT1 null genotype but 30 percent of the patients with GSTT1-positive genotype had liver metastasis (p < 0.01) but GSTT1 genotype was not associated with survival. Sputum (p < 0.01) was more common in patients with GSTM1 null genotype. Subjects with the GSTM1-null genotype had shorter survival. Using a Cox proportional hazard model, GSTM1, tumor (T) factor and thoracic irradiation status were identified as independent prognostic factors. CONCLUSIONS: Our preliminary results showed that GSTM1-null genotype was associated with shorter survival.     

肝细胞癌、鼻咽癌患者谷胱甘肽硫转移酶m和T1基因型分布

Objective: The aim of our study was to investigate the distribution of glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) gene polymorphism in hepatocellular carcinoma (HCC) and nasopharyngeal carcinoma (NPC) patients in a high risk area in Guangxi Zhuang Autonomous Region, China.Methods: It was a case-control study.The genotypes of GSTM1 and GSTT1 in 181 HCC and 126 NPC patients were compared with 641 matched control.The GSTM1 and GSTT1 genotypes were detected using conventional multiplex PCR method.Results: The frequency of GSTM1 null genotype in HCC, NPC and control groups were 65.2%, 61.9% and 47.6% respectively, significant difference between these two cancer groups and control was observed (P < 0.01).The frequency of GSTT1 null genotype in HCC, NPC and control groups were 57.5%, 62.7% and 43.1% respectively, significant difference between these two cancer groups and control was observed (P < 0.01).Conclusion: The distributions of GSTM1 and T1 genes are polymorphic in HCC and NPC patients in a high risk area in Guangxi, individuals with GSTM1-null or GSTT1-null would have an increasing risk of developing HCC and NPC, especially when combination with virus infection (HBV or EBV) and absorbed chemical toxin (AFB1 or cigarette).     

GSTM1 polymorphism and oral squamous cell carcinoma

We investigated the frequency of the GSTM1 genotypes in 70 Brazilian patients with oral squamous cell carcinoma (OSCC) and 82 age-sex matched controls. The GSTM1 genotypes were studied by PCR-based methods. The frequency of male patients with OSCC and null for the GSTM1 (70.5%) was statistically different from the male patients from the control group (48.5%) (Odds Ratio, OR=2.53, 95% CI=1.22-5.24, P<0.05). The frequency of the GSTM1 null genotype (0/0) in the group with OSCC (65.7%) was statistically different from the controls (48.7%) (OR=2.01, 95% CI=1.04-3.88, P<0.05). The prevalence of GSTM1 deficiency (null) was significantly higher for patients with oral cancer of the floor of the mouth (OR=3.67, 95% CI=1.11-12.11, P<0.05). In conclusion, the GSTM1 null genotype may increase the risk for OSCC development.     

STUDY OF THE DELETION MUTATION OF GLUTATHIONE S TRANSFERASE M1 GENE AND ITS ROLE IN SUSCEPTIBILITY TO HEPATOCELLULAR CARCINOMA

The severe aflatoxin B1 contamination as the main cause of hepatocellular carcinoma in Guangxi had been proposed by many researches. The 8, 9-epoxide aflatoxin is the metabolized product of aflatoxin B1 in liver and can covalently bind to guanine forming AFB1-N7-Gua adduct which was believed to induce G-T transversion mutation in experimental animals, as well as to activate protooncogene ras and result in p53 gene aberration. In general thinking, the detoxification of carcinogens with epox…