广西扶绥县肝癌高发家系谷胱甘肽转硫酶GSTM_1和GSTT_1基因多态性的研究

目的探讨广西扶绥县肝癌高发区壮族人群谷胱甘肽转硫酶GSTM1和GSTT1的基因多态性在肝癌家族聚集性中的作用,以及一级亲属与先证者之间HCC易感性的关系。方法采用病例-对照研究方法,收集21个广西扶绥县壮族肝癌家系76例,以及该地区21个对照家系68例,采用多重PCR技术和凝胶成像分析方法,对入选者GSTM1和GSTT1基因型进行检测,用ELISA法检测HBsAg,并将实验结果与临床资料相结合,进行统计学分析。结果①GSTM1基因空白型在肝癌家系组、对照家系组之间的频率分别为67.1%和36.8%(P=0.000);GSTT1基因空白型在肝癌家系组、对照家系组之间的频率分别为40.8%和19.1%(P=0.005);GSTM1和GSTT1基因同时缺失在肝癌家系组、对照家系组的频率分别为31.6%和2.9%(P=0.000)。②将GSTM1及GSTT1基因同时表达型为基准计算两基因联合作用的危险度,GSTM1基因缺失GSTT1基因表达型、GSTM1基因表达GSTT1基因缺失型、GSTM1基因及GSTT1基因联合缺失型的OR值分别为0.102、0.210和3.092。③GSTM1基因空白型在先证者与其直系亲属之间的频率分别为71.4%和65.5%(P=0.620),GSTT1基因空白型在先证者与其直系亲属之间的频率分别为47.6%和38.2%(P=0.454)。GSTM1和GSTT1基因同时缺失在先证者与其直系亲属之间的频率分别为33.3%和30.9%(P=0.839),差异均无统计学意义(P>0.05)。结论①GSTM1和GSTT1基因的多态性与肝癌家族聚集性相关;②GSTM1和GSTT1基因联合缺失与HCC的发生呈显著正相关,且两基因可能具有协同作用;③直系亲属与先证者HCC发生率无差别。     

广西肝细胞癌GSTM1基因多态性研究

目的：研究黄曲霉毒素高危区谷胱甘肽转移酶Ｍ１（ＧＳＴＭ１）基因多态性与肝细胞癌的相关性，验证该指标作为肝细胞癌预报因子的可靠性。方法：用特异性引物与ＰＣＲ技术，检测不同地区正常人、高污染区肝细胞癌患者的ＧＳＴＭ１缺失的基因型频率。结果：黄曲霉毒素高危区肝细胞癌患者与正常人的ＧＳＴＭ１基因缺失频率分别为５９％和５２％，无显著性差异；但与肝细胞癌低发地区正常人相比，其基因缺失频率较高，差异具有显著性意     

广西扶绥县壮族肝癌家系人群Itgb1基因多态性与肝癌遗传易感性的研究

目的 研究广西扶绥县壮族肝细胞癌(hepatocellular carcinoma,HCC,以下简称肝癌)高发家系人群Itgb1基因rs2298141位点单核苷酸多态性(single nucleotide polymorphism,SNP)和肝癌遗传易感性的关系.方法 采用病例-对照研究方法,选择扶绥县20个肝癌高发家系共79例(肝癌高发家系组)和10个正常对照家系共40名(正常对照家系组)为研究对象,应用时间飞行质谱技术(MALDI-TOF MS)检测两组Itgb1基因rs2298141位点的基因型及等位基因频率,并应用非条件logistic回归分析该位点基因多态性与肝癌遗传易感性的关系.结果 正常对照家系组人群携带AA、AG、GG基因型频率分别为40.00％、47.50％、12.50％.肝癌高发家系组人群携带AA、AG、GG基因型频率分别为50.00％、40.00％、10.00％;两组Itgb1基因rs2298141位点各基因型频率与期望值吻合度较好(P＞0.05),符合Hardy-Weinberg遗传平衡定律.正常对照家系组人群中AG、GG基因型个体罹患肝癌的风险分别是AA基因型个体的0.67倍(95％CI:0.22～2.1,P=0.50)和1.05倍(95％CI:0.17～6.6,P=0.96);肝癌高发家系组人群中未患肝癌者AG、GG基因型个体罹患肝癌的风险分别是AA基因型个体的0.91倍(95％CI:0.31～2.71,P=0.86)和2.2倍(95％CI:0.40～11.96,P=0.37),但差异无统计学意义(P＞0.05).结论 广西扶绥县壮族人群中Itgb1基因rs2298141位点的SNP与罹患肝癌无明显相关性.     

GSTM1、GSTT1基因多态性和饮酒习惯与原发性肝癌发生的危险性

目的　研究GSTM 1和GSTT 1基因的多态性和饮酒习惯与原发性肝癌发生的危险性。方法　在肝癌高发区江苏省泰兴市进行了以人群为基础的病例对照研究 ,并应用多重PCR法检测了 2 0 7例原发性肝癌及其 1∶1配对的正常对照的GSTM 1和GSTT 1基因型。结果　GSTM 1空白基因型的频率 ,病例组为 5 8.94% ,对照组为 5 7.0 0 % ;GSTT 1空白基因型的频率 ,病例组和对照组分别为 5 2 .17%和 46.86% ,2组间无显著性差异。但GSTT 1的空白基因型与非空白基因型相比 ,当其长期饮用高度白酒达2 3年以上或月饮酒量大于 3 0 0 0 g时 ,患肝癌的危险性显著增高 (OR =2 .5 6,95 %CI为 1.0 8～ 6.0 5或OR =3 .48,95 %CI为 3 1.47～ 8.2 2 ) ;此外分析饮酒总量 (kg·年 )也得到同样的结果 (OR =3 .71,95 %为 1.5 1～ 9.12 )。结论　携带GSTT 1空白基因型且有长期大量饮酒习惯者 ,其患肝癌的危险性显著增高     

谷胱甘肽转硫酶T1、M1基因型和烟酒茶嗜好与食管癌、胃癌

目的：研究谷胱甘肽转硫酶T1、M1（GSTT1、GSTM1）基因多态性和烟酒茶嗜好及其相互作用与食管癌，胃癌易感性的关系。方法：在上消化道癌高发区淮安市进行了病例－对照研究（食管癌141例，胃癌153例；人群对照223例），调查研究对象的烟酒茶嗜好习惯，以多重PCR方法分析GSTT1、GSTM1基因型。结果：食管癌组GSTM1－基因型频度（75．18％）显著高于对照组（59．64％，P＝0．0024）；多因素调整OR＝2．33，95％CI＝1．39－3．92）。吸烟或不饮茶与GSM1－基因型在增加食管癌发生的风险中有明显的协同作用。在GSTT1＋基因型者中，吸烟习惯显著增加食管癌，胃癌的危险性；在GSTM1＋基因型者中，经常饮酒显著增加食管癌、胃癌的危险性。结论：食管癌、胃癌的发生与生活习惯，GSTM1和GSTT1基因型以及它们的相互作用有关。     

谷胱甘肽硫转移酶M1基因多态性与食管癌Meta分析

[目的]综合评价谷胱甘肽硫转移酶M1(GSTM1)基因多态性与食管癌易患性的相关性。[方法]应用Meta分析方法对国内外9篇有关GSTM1因多态性与食管癌的病例对照研究进行定量综合分析，共积累病例845例，对照1267例。统计处理采用Meta分析的固定效应模型和随机效应模型。[结果]在排除一个超溢值后，8个病例对照研究的合并OR为1．622，95％可信度为1．323～1．988。[结论]GSTM1基因多态性与食管癌的易患性有关，即GSTM1空白基因型可增加患食管癌的危险性。     

广西壮族人群GSTM1和GSTT1基因多态性与肺癌易感性关系的研究

[目的]探讨广西壮族人群谷胱甘肽硫转移酶（glutathione S-transferase,GST）中的GSTM1和GSTT1基因多态性与肺癌易感性的关系。[方法]以病例对照研究方法,采用聚合酶链式反应（PCR）分别检侧58例肺癌患者和60例健康对照的GSTM1、GSTT1基因多态性;χ2检验分析各种基因型频率在肺癌组和对照组之间的差异;用Logistic回归分析吸烟与GSTM1、GSTT1基因型多态性的联合作用。[结果]单独分析GSTM1、GSTT1基因多态性与肺癌相关性无统计学意义,而两者联合则与肺癌有相关性（χ2=4.085,P=0.043）。吸烟与GSTM1缺陷型基因对肺癌易感有协同作用,OR为3.778（95%CI：1.170～12.194,P=0.026）;吸烟与GSTT1缺陷型基因对肺癌易感无协同作用,OR为2.833（95%CI：0.982～8.173）。[结论]GSTM1、GSTT1的单一基因多态性不增加患肺癌的危险,而两者联合作用时可增加患肺癌的风险。GSTM1缺陷型有吸烟行为的人更易患肺癌。     

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。     

上海地区白血病谷胱甘肽S-转移酶T1和M1基因多态性分析

目的 研究谷胱甘肽S-转移酶(GSTs)T1、M1基因多态形态在上海地区白血病患者中的频率分布特征,探讨不同基因多态形态与白血病易感性之间的联系。方法 采用等位基因特异聚合酶链反应(AS-PCR)方法对上海地区61名白血病患者进行GSTF1、M1基因型分析,比较不同基因型在白血病组和同一地区正常人群组之间的分布频率差异,并就疾病类型、年龄和性别进行分层比较。结果 白血病组和正常对照组之间,GSTT10／0基因型以及GSTT10／0-GSTM10／0联合基因型的分布频率差异有显著性,缺损基因型在白血病组显著升高。进行疾病类型、性别以及年龄分层后,这种趋势在男性和低年龄(≤30岁)急性淋巴细胞白血病患者中依然存在。结论 GSTF10／0基因型和GSTT10／0-GSTM10／0联合基因型可能是罹患白血病的风险因子。     

GSTM1、GSTT1基因多态性与家族聚集性肝癌的遗传易感性研究

目的探讨GSTM1、GSTT1基因多态性与家族聚集性肝癌遗传易感性的关系。方法应用PCR技术检测GSTM1、GSTF1在家族聚集性肝癌和肝癌高发家系的基因表型。结果家族聚集性肝癌组GSTM1（-）、GSTT1（-）基因型频率分别为68．8％、47．5％,显著高于非家族聚集性肝癌组（54．6％、30．8％）和对照肝组织组（53．3％、25．3％）（P〈0．05）;随着家族中患肝癌病例数的增加,GSTM1（-）、GSTT1（-）基因型的频率逐渐升高,肝癌高发家系组GSTM1（-）、GSTT1（-）基因型频率分别为68．1％和44．9％,显著高于对照家系组（47．5％、25．0％）（P〈0．05）。若将GSTM1（-）T1（-）基因型视为危险暴露因素．．家族聚集性肝癌组GSTM1（＋）T1（＋）和GSTM1（＋）T1（-）／GSTM1（-）T1（＋）基因型频率均显著低于非家族聚集性肝癌组和对照肝组织组（P〈0．01）。结论GSTMI、GSTF1遗传多态性与家族聚集性肝癌的遗传易感性有关,GSTM1（-）、GSTT1（-）基因型可能是肝癌家族成员的危险暴露因素。     

Frequency and Association Of GSTM1 and GSTT1 Gene Polymorphisms with Survival in Breast Cancer Patients

Objective: Glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) are the key detoxification enzymes of xenobiotics, including chemotherapeutic drugs. The deletion polymorphisms of GSTM1 and GSTT1 genes are associated with reduced enzyme activity that influenced clinical outcomes of chemotherapeutic agents in breast cancer. However, there is limited information among Thai patients. This research aims to explore the frequency and role of GSTM1 and GSTT1 polymorphisms on survival among Thai patients with breast cancer. Methods: The retrospective cohort study was performed. Demographic data and clinicopathology characteristics were collected from hospital base registry data and medical records. A multiplex qualitative real-time PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 gene in the genomic DNA samples of the participants. Results: The frequencies of the GSTM1 and GSTT1 null genotypes in 198 breast cancer patients were 65.70% and 33.30%, respectively. The overall survival at 1, 3 and 5 years were 95.00%, 83.00%, 71.00% respectively. The log rank test and Cox proportional hazards revealed a significant different in the 5-years overall survival according to lymph node metastasis and tumor stage (P = 0.014 and P < 0.001). No associations between overall survival and GSTM1 or GSTT1 genotype were found in single or combined genotypes analyses (P = 0.76 and P= 0.15). Conclusion: The results of our study provided the epidemiological information for prognostic of survival in breast cancer patients treated with chemotherapy.     

GSTM1、GSTT1基因多态性对宫颈癌患者新辅助化疗疗效及预后的影响

目的:研究谷胱苷肽硫转移酶M1（GSTM1）、谷胱苷肽硫转移酶T1（GSTT1）基因多态性对新辅助化疗（NACT）宫颈癌患者疗效的影响及与患者预后的关系。方法:选取2011年5月至2013年5月本院诊治的宫颈癌患者78例为研究对象,NACT采用铂类和紫杉醇类药物,GSTM1、GSTT1基因多态性检测采用多重PCR技术。结果:GSTM1和GSTT1基因在宫颈癌患者中呈多态性分布,GSTM1、GSTT1非缺失组患者总有效率显著高于GSTM1、GSTT1缺失组（P＜0.05）。GSTM1、GSTT1缺失组患者5年生存率显著低于GSTM1、GSTT1非缺失组患者（P＜0.05）。GSTM1、GSTT1基因缺失是影响NACT宫颈癌患者不良预后发生的独立危险因素（P＜0.05）。结论:不同GSTM1、GSTT1基因分型下,NACT对宫颈癌患者的疗效有显著差异,GSTM1、GSTT1基因缺失是影响NACT宫颈癌患者不良预后发生的独立危险因素。     

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) Polymorphisms and Lung Cancer Risk among a Select Group of Iranian People

Objective(s): Lung cancer, caused primarily by smoking, is one of the leading determinants of mortality throughoutthe world. Here we investigated the effects of polymorphisms in two enzymes, i.e., GSTT1 and GSTM1, related tothe antioxidant defense line against carcinogens associated with lung cancer among a select group of Iranian people.Materials and Methods: One hundred and twenty lung cancer patients from two referral centers in Tehran, Iran, wererecruited for comparison with 120 healthy controls. Genomic DNA was extracted from the FFPE tumor tissues ofthe select cases and peripheral blood buffy coats of healthy controls. The polymorphisms of GSTT1 and GSTM1 wereinvestigated by multiplex polymerase chain reaction. Results: With the 240 samples studied, no specific relationshipwith lung cancer was discerned for the GSTM1 (P=0.35; OR=1/33; 95% CI=0.79-2.25) polymorphism, but the GSTT1(P=0.005; OR=2.4; CI=1.32-4.35) gene polymorphism revealed a notable association on logistic regression, takinginto account age and sex factors. Furthermore, the GSTT1 genotype distribution in patients with LSCC was differentfrom that of healthy cases (P=0.006; OR=3.11; CI=1.38-7.04). The risk of developing lung cancer with the T0M1genotype was 3.46 times higher than with T1M1 genotype (P=0.002; OR=3.46; CI=1.61-7.46). Moreover, the risk ofdeveloping LSCC cancer in people with T0M1 genotypes was significantly elevated (P=0.004; OR=4.5; CI=1.62-12.52).Conclusion: Unlike GSTM1, the GSTT1 genotype distribution is associated with the incidence of lung cancer in Iranianpeople. Different types of lung cancer appear to show various correlations with GST polymorphisms in this regard.     

Meta-analysis of the association between GSTM1 and GSTT1 gene polymorphisms and cervical cancer

Aim: We conducted a meta-analysis to analyze the influence of GSTM1 and GSTT1 gene polymorphisms on cervical cancer risk, and explore gene-environment interactions. Methods: Identification of relevant studies was carried out through a search of Medline and the EMbase up to Oct. 2011. All case-control studies that investigated the association between GSTM1 and GSTT1 gene polymorphisms and risk of cervical cancer were included. The pooled odds ratio (OR) was used for analyses of results and the corresponding 95% confidence intervals (CI) were estimated. Results: A total of 21 case-control studies were included in the meta-analysis of GSTM1 (2,378 cases and 2,639 controls) and GSTT1 (1,229 cases and 1,223 controls) genotypes. The overall results showed that the GSTM1 null was related to an increased risk of cervical cancer (OR=1.50, 95% CI=1.21-1.85). Subgroup analysis were performed based on smoking and ethnicity. Our results showed that smokers with null GSTM1 genotype had a moderate increased risk of cervical cancer (OR=1.85, 95% CI=1.07-3.20). For the ethnicity stratification, moderate significantly increased risk of null GSTM1 genotype was found in Chinese (OR=2.12, 95% CI=1.43-3.15) and Indian populations (OR=2.07, 95% CI=1.49-2.88), but no increased risk was noted in others. Conclusion: This meta-analysis provided strong evidence that the GSTM1 genotype is associated with the development of cervical cancer, especially in smokers, and Chinese and Indian populations. However, no association was found for GSTT1 null genotype carriers.     

四川北部地区肺癌患者GSTT1基因多态性分析

目的:了解四川北部地区汉族肺癌人群GSTT1基因多态性状况,与其他地区人群人种进行比较。方法:采用聚合酶链式反应(PCR)技术检测该地区肺癌患者GSTT1基因缺失〔GSTT1(-)〕频率。结果:本地区肺癌患者GSTT1(-)频率为45%(45/100),其中纯和缺失率女性和男性分别为52.0%(13/25)和42.7%(32/75),χ2=0.660,P=0.417;鳞癌38.1%(16/42),腺癌48.0%(12/25),χ2=0.632,P=0.427;吸烟者44.4%(28/63),不吸烟者45.9%(17/37),χ2=0.021,P=0.884。结论:本地区肺癌患者GSTT1基因缺失频率高于欧美,与亚洲多中心研究结果类似,缺失频率与性别、病理类型及是否吸烟无关。     

原发性肺癌GSTM1基因多态性与化疗效果关系的研究靠

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。     

Glutathione S-transferases (GSTT1 and GSTM1) genes polymorphisms and the treatment response and prognosis in Chinese patients with de novo acute myeloid leukemia

We investigated the prognostic significance of genetic polymorphism for glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase mu 1 (GSTM1) in 254 Chinese patients with de novo acute myeloid leukemia (AML) other than AML-M3. The early death rate after the initiation of chemotherapy was similar between the GSTT1+/GSTM1+ group and GSTT1−/GSTM1− group. The complete remission (CR) rate was higher in GSTM1+ group than in GSTM1− group (OR = 1.88; P = 0.03) after the first course of chemotherapy, and was higher in GSTT1+ group than in GSTT1− group (OR = 2.20; P = 0.02) after the second course of chemotherapy. Overall survival and disease-free survival of CR patients in GSTT1 and GSTM1 double present group was better than in GSTT1- and/or GSTM1-group (P = 0.03 and 0.02, respectively). Our preliminary results warrant testing of a larger number of patients.     

洛阳市GSTM1和GSTT1缺失基因型与肝癌的遗传易感性

目的探讨肝癌低发区谷胱甘肽转硫酶(GST)M1和T1的缺失基因型与肝癌的关系.方法应用多重PCR技术检测洛阳市95例肝癌患者和103例对照的GSTM1和GSTT1基因型.结果病例组GSTM1缺失基因型的频率为0.705,对照组为0.502,两者差异有显著性(x2=8.28,P=0.004),OR值为2.35(95%CI:1.25～4.41);病例组GSTT1缺失基因型的频率为0.611,对照组为0.437,两者差异有显著性(x2=5.97,P=0.015),OR值为2.02(95%CI:1.10～3.71).叉生分析表明该两因素在肝癌发生中有协同作用(x2=14.83,P=0.002),同时具有两个缺失基因型时,OR值为5.57(95%CI:2.03～15.66);GSTM1和GSTT1缺失基因型均与吸烟有协同作用,OR值分别为5.84(95%CI:2.26～15.47)和5.51(95%CI:2.13～14.54);GSTM1缺失基因型与饮酒有协同作用,OR值为3.31(95%CI:1.47～7.49),而GSTT1缺失基因型与饮酒无协同作用.结论在肝癌低发区GSTM1和GSTT1缺失基因型是肝癌的易感基因型.     

谷胱苷肽S转硫酶T1、M1和P1基因多态性与结直肠癌易感性的关系

目的研究谷胱苷肽S转硫酶T1、M1和P1(GSTT1、GSTM1和GSTP1)多态性与结直肠癌易感性的关系。方法在江苏省进行了1个病例—对照研究(结直肠癌患者315例,人群对照439例),调查研究对象的生活习惯,抽取静脉血,提取白细胞DNA,以多重PCR技术检测GSTT1和GSTM1基因缺失,PCR-RFLP技术检测GSTP1基因单核苷酸多态(第104密码子A→G)。结果①在结直肠癌组和正常组GSTT1和GSTM1基因缺失频率分别为55.24%、57.31%和72.70%、73.29%、差异无显著性。②在结直肠癌组GSTP1 A/A、A/G和G/G基因型分布频度分别为57.51%、36.74%和5.75%;对照组分别为63.70%、31.05%和5.25%,2组之间差异无显著性(χ2 MH=2.993,P=0.224)。与GSTP1 A/A基因型携带者相比,G/G基因型者发生结直肠癌的危险性无显著升高,其性别、年龄、吸烟、饮酒习惯调整后的OR为1.09(95%CI:0.79~1.51)。结论GSTT1、GSTM1基因缺失型和GSTP1 G/G基因型与结直肠癌的易感性无显著相关。