中国南方粤语方言地区汉族人群GSTM1、GSTT1基因多态性

背景与目的:了解谷胱甘肽-S-转移酶M1、T1(GSTM1、GSTT1)基因多态性在中国南方粤语方言地区健康人群中的分布规律,初步探讨其与人群某些疾病家族史之间的关系。材料与方法:根据研究目的在广东省新兴县和广东省广州市两个地区选择符合条件的健康人群606人作为研究对象。应用聚合酶链式反应-2%琼脂糖凝胶电泳的方法检测调查对象GSTM1、GSTT1基因型。结果:在调查人群中,GSTM1基因纯合缺失基因型GSTM1(-/-)的出现频率为56.8%(n=597);GSTT1基因纯合缺失基因型GSTT1(-/-)的出现频率为42.1%(n=579);两基因联合缺失的频率为22.8%(n=570)。结论:GSTM1与GSTT1基因之间在人群中分布相互独立,无连锁现象,GSTM1基因在两个不同地区来源人群中的分布有显著差异。GSTT1在人群中不同基因型的分布与研究人群中冠心病疾病家族史的发生之间显著关联,有冠心病家族史人群GSTT1缺失基因型的表达显著增加。     

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。     

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、GSTM 1)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 15 3例 ;人群对照 2 2 3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 (5 9.6 4 % ,P =0 .0 0 2 4 ;多因素调整OR =2 .33,95 %CI =1.39～ 3.92 )。吸烟或不饮茶与GSTM 1 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。     

外周血CYP3A和GSTM1基因多态性检测对头颈部NHL化疗效果预测意义的分析

目的:研究CYP3A和GSTM1基因多态性与非霍奇金淋巴瘤(NHL)化疗疗效、毒副作用之间的相关性.方法:收集初治90例头颈部NHL患者和60名正常人及60例非肿瘤住院患者的外周静脉血,提取DNA,以PCR技术检测CYP3A和GSTM1等位基因型,采用CHOP方案治疗患者,比较不同的基因型患者化疗疗效和毒副作用的差别.结果:NHL患者CYP3A突变基因(A-44)频率为66.7％,GSTM1缺失基因频率为58.9％,与正常人两种基因型的分布频率(62.5％和53.3％)差异无统计学意义,x2值为1.114和0.643,P值均＞0.05.W和WM基因型的有效率分别为100.0％(4/4)和92.3％(48/52),均明显高于M基因型患者的29.4％(10/34),x2值分别为4.930和37.037,P值均＜0.05;含GSTM1非缺失基因型(+)的患者(0+Ⅰ期+Ⅱ期)白细胞下降89.2％,缺失基因型(-)患者(0+Ⅰ+Ⅱ期)白细胞下降67.9％,差异有统计学意义,P＜0,05.结论:CYP3A和GSTM1基因多态性不增加NHL的患病风险,但能影响NHL患者化疗疗效及毒副作用.     

GSTM1和CYP2E1基因多态性与肺癌遗传易感性关系的研究

背景与目的肺癌是中国人群恶性肿瘤死因的首位，其发病可能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P4502E1(CYP2E1)基因RsaⅠ／PstⅠ多态性和谷胱甘肽转移酶M1(GSTM1)基因多态性与肺癌易感性之间是否存在相关性。方法应用PCR-RFLP和PCR法检测99例人非小细胞肺癌患者和66例同期住院的肺良性疾病患者CYP2E1基因的RsaⅠ／PstⅠ多态性和GSTM1基因多态性，并分析其与肺癌遗传易感性的相关性。结果(1)CYP2E1基因RsaⅠ／PstⅠ多态性的三种基因型在肺癌组和对照组的频率差异没有统计学意义(χ^2=1．374，P=0．241)。(2)肺癌组GSTM1(-)基因型频率显著高于对照组(分别为57．6％和40．9％)(χ^2=4．401，P=0．036)。(3)携带GSTM1(-)基因型的个体患肺癌的危险性显著高于GSTM1( )基因型的个体(OR=1．96，95％CI=1．042～3．689，P=0．037)。(4)与携带c1／c2或c2／c2基因型的不吸烟个体比较，携带c1／c1基因型的吸烟者患肺癌的风险显著增加(OR=3．525，95％CI=1．168～10．638，P=0．025)。(5)联合分析CYP2E1基因RsaⅠ／PstⅠ多态性和GSTM1基因多态性，携带有c1／c1和GSTM1(-)基因型的个体患肺癌的风险显著高于携带GSTM1( )和c1／c2或c2／c2基因型的个体(OR=3．449，95％CO=1．001～11．886，P=0．050)。按照吸烟因素分层，携带有GSTM1(-)和c1／c1基因型的不吸烟个体患肺癌的风险显著高于携带GSTM1( )和c1／c2或c2／c2基因型的不吸烟个体(OR=11．553，95％CI=1．068-124．944，P=0．044)，携带有GSTM1(-)和c1／c2或c2／c2基因型的不吸烟个体患肺癌的风险同样显著高于携带GSTM1( )和c1／c2或c2／c2基因型的不吸烟个体(OR=13．374，95％CI=1．258～142．166，P=0．032)。结论(1)GSTM1(-)基因型增加人群患肺癌的风险；(2)CYP2E1的c1／c1基因型和GSTM1(-)基因型的联合可增加吸烟和不吸烟人群患肺癌的风险。     

GSTM1基因多态性与鼻咽癌遗传易感性的关系研究

目的　探讨谷胱甘肽S转移酶M 1(GSTM 1)基因多态性与鼻咽癌 (NPC )遗传易感性的关系。方法　采用内参照PCR法检测 80例NPC患者的GSTM 1基因型。结果　NPC患者GSTM 1空白基因型频率为 60 .0 % ,对照组为 45 .0 % ,两者有显著性差异 (P <0 .0 5 ) ,其OR =1.83 3 ( 95 %CI =1.0 46～ 3 .14 7) ;鳞癌的空白基因型频率为 60 .5 % ,明显高于腺癌的 5 0 .0 % (P <0 .0 1) ;吸烟者空白基因型个体患鼻咽癌的危险性显著增加 [OR =2 .813 ( 1.3 5 8～ 6.0 12 ) ,P <0 .0 1] ,而不吸烟者的危险性增加不明显 (P >0 .0 5 )。结论　GSTM 1基因多态性与NPC患者的遗传易感性有关 ,与NPC的病理类型有关 ,吸烟者的GSTM 1空白基因型个体更易患NPC。     

广西扶绥人群GSTM1和GSTT1基因多态性与肝癌易感性关系的研究

目的:探讨GSTM1和GSTT1基因多态性与肝癌易感性关系,以及基因与基因间的相互作用.方法: 应用病例-对照分析研究,采用多重PCR技术,对广西扶绥100例肝细胞癌患者、60例正常人群的GSTM1和GSTT1基因型进行检测.将实验结果与临床资料结合进行统计学分析.结果: GSTM1基因空白型在HCC组和正常对照组中的频率分别为59.0%、68.3%(P>0.05);HCC组GSTT1基因缺失频率(33.0%)显著高于正常对照组(18.3%);GSTM1和GSTT1基因同时缺失在肝癌组和对照组中的频率分别为22.0%和3.3%,两者差异有统计学意义.结论:1)GSTM1和GSTT1基因的缺失是通过遗传获得.2)GSTT1基因缺失是HCC的易感因素.3)GSTM1和GSTT1基因联合缺失与HCC的发生呈显著正相关,且两基因具有协同作用,可作为HCC高危人群筛选的有用指标.     

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     

Ⅱ相代谢酶基因多态性与广西肝癌发生的关系

目的　探讨Ⅱ相代谢酶谷胱甘肽硫转移酶M 1、T 1(GSTM 1、GSTT1)及微粒体环氧化物水解酶 (mEH )基因多态性与广西肝癌易感性的关系 ,以及基因与基因间的相互作用。方法　采用多重PCR、PCR RFLP技术 ,对广西地区 10 5例肝癌患者及 15 1例健康对照的GSTM 1、GSTT 1、mEH基因型进行检测。结果　GSTM 1基因缺失率在病例组与对照组中分别为 64 .76%和5 0 .99% ,两者比较有显著性差异 (P <0 .0 5 ,OR =1.77) ;病例组GSTT 1基因缺失率 (4 0 .95 % )高于对照组 (3 3 .11% ) ,mEH 3种基因型频率在病例组分别为 2 7.62 %、2 1.90 %、5 0 .48% ,对照组则分别为 2 1.19%、3 4.44 %、44 .3 7% ,两组比较无显著性差异 (P >0 .0 5 ) ;GSTM 1、T 1基因同时缺失的个体患肝癌的危险性增大了 1.2 2倍。结论　GSTM 1、T1基因同时缺失是肝癌的易感因素 ,可作为肝癌高危人群筛选的标记物。     

CYP1A1,GSTM1基因型与烟酒诱发人体内淋巴细胞微核的形成

目的: 探讨代谢酶CYP1A1和GSTM1等位基因型对烟酒诱发人体内淋巴细胞微核的影响.方法:分别应用等位基因特异性(AS)和多重差别(MD)-PCR检测CYP1A1和GSTM1的等位基因型,应用末梢血微核法检测体内淋巴细胞微核.结果:与无吸烟史健康人群的淋巴细胞平均微核率(MNF 0.24‰)相比,吸烟组MNF显著增加(0.65‰,P＜0.05),重度饮酒可增强这一效应(0.89‰,P＜0.01):与无吸烟史的非易感联合基因型(CYP1A1 I1e/I1e*GSTM1+(+/+和+/0),CYP1A1 I1e/I1e*GSTM1 0/0和CYP1A1 I1e/Val*GSTM1+)个体的MNF(0.42‰)相比,吸烟使GSTM1 0/0基因型个体的MNF显著上升(0.75‰,P＜0.05),并可使CYP1A1 Val/Val基因型和易感联合基因型(CYP1A1 I1e/Val*GSTM1 0/0,CYP1A1 Val/Val*GSTM1+和CYP1A1 Val/Val*GSTM1 0/0)个体的MNF均上升约1倍(0.83‰和0.85‰,0.10＞P＞0.05).结论:吸烟诱发体内淋巴细胞MNF显著增加,重度饮酒增强这一效应.烟酒诱发微核形成与个体CYP1A1和GSTM1的遗传多态性密切相关.     

肝细胞癌患者的谷胱甘肽硫转移酶基因缺失的研究

目的　研究广西黄曲霉毒素B1(AFB1)高污染区人群谷胱甘肽硫转移酶GSTM 1和GSTT1基因缺失多态性与肝细胞癌高发的相关性。方法　采用聚合酶链反应 (PCR)方法检测 110例高污染区肝细胞癌患者和 135例无癌健康对照者的GSTM1和GSTT1基因型分布。结果　正常对照组GSTM 1和GSTT1基因缺失率分别为 4 7.4 %和 4 0 .7% ,肝细胞癌组GSTM 1和GSTT1基因缺失率分别为 6 3.6 %和 6 0 .0 % ;GSTM 1基因缺失在肝细胞癌组和正常对照组之间 ,差异具有显著性意义 (P <0 .0 5 ) ;GSTT1基因缺失在肝细胞癌组和正常对照组之间差异具有非常显著性意义 (P <0 .0 1)。结论　肝细胞癌患者GSTM1和GSTT1基因缺失水平偏高可能是易感的原因之一。     

Genetic polymorphism of gluthation-S transferases and N-acetyl transferases 2 and nasopharyngeal carcinoma: the Tunisia experience

Interindividual differences observed in the metabolism of xenobiotics have been attributed to the genetic polymorphism of genes, which code for enzymes involved in detoxification. This genetic variability seems to be associated with the individual's susceptibility to certain cancers, including nasopharyngeal carcinoma. In this study, we have investigated the genotypic frequencies of DNA polymorphisms of two detoxification's genes: the gluthatione-S-transferase (GST) and the N-acetyl transferase 2 (NAT2). The study has included 45 patients with nasopharyngeal carcinoma compared to 100 healthy Tunisian controls. The presence of the GSTM1 null and GSTT1 null polymorphism was screened by using a multiplex PCR procedure. A PCR-RFLP method was used to detect polymorphism for the most common alleles of the NAT2 gene. Allelic frequencies between the two groups were compared using a chi2 test and odds ratio with 95% confidence intervals were calculated. The results indicate that the genotypic frequency of GSTM10/0 between controls and patients was significantly different. This genotype confers an increased risk of nasopharyngeal carcinoma (Odds Ratio = 2.12, [0.64-4.7]). However, genotypic frequencies of NAT2*6/NAT2*6 were significantly higher in the group of nasopharyngeal carcinoma patients. The calculated Odds Ratio showed an association between this genotype and nasopharyngeal carcinoma. In conclusion, the increase of nasopharyngeal carcinoma risk in Tunisia seems to be associated with GSTM10/0 and NAT2*6/6 genotype.     

Genomic Pattern of GSTM1 and T1 Gene Null polymorphism of Head and Neck Cancer Patients in Eastern India

Objective: Homozygous deletion i.e., null polymorphism of the Glutathione S transferases genes hinders detoxification reactions by altering the sensitization of glutathione s transferases enzymes. Hence, we analysed the association between the GSTM1 and GSTT1 gene polymorphisms and head and neck cancer (HNC). Methods: The study consists of 238 healthy controls and 160 diagnosed cases of HNC, who attended the Regional Cancer Centre, Indira Gandhi Institute of Medical Sciences (a tertiary care hospital). DNA was extracted from whole blood of patients and control using Qiagen DNA extraction kit. GSTM1 and GSTT1 gene polymorphisms were examined using PCR and agarose gel electrophoresis. Results: GSTM0 null polymorphism was 26.25% and 15.13% in cases and control respectively. GSTT0 null polymorphism was observed in 18.13% cases and 8.82% in control groups. The GSTM0 null polymorphism was present significantly in case group as compared to control group (OR = 1.997, p = 0.006). There was also significant association of GSTT0 null polymorphism with case group as compared to control group (OR = 2.288, p = 0.006). The combined genotypes were also analysed. GSTM0T1 genotype (n = 27) was found to be most common among HNC group followed next by GSTM0T0 double deletion (n =15). Conclusion: The result indicated that there was strong association of GSTM0 and GSTT0 null polymorphism in those patients. The combined genotypes i.e., GSTM0T1 and GSTM0T0 null polymorphism also showed significant association in HNC patients.     

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…     

GSTM1 and GSTT1 polymorphisms,tobacco use as risk factors for nasopharyngeal carcinoma in maghreb population — A case-control study

Nasopharyngeal carcinoma (NPC) has known environmental risk factors, notably smoking, and enzymes that biotransform carcinogens. The interindividual differences observed in the metabolism of tobacco carcinogens substances have been attributed to the genetic polymorphism of genes, which code for enzymes involved in detoxification. Polymorphic deletions of GSTM1 and GSTT1 genes involved in the detoxification of potentially carcinogenic agents may be a risk factor for NPC. To investigate the roles of genetic variations of GSTM1 and GSTT1 in NPC susceptibility in the Northern African population, we conducted a case-control study of 132 NPC cases and 200 controls. DNA was isolated from blood for cases and controls. GSTM1 and GSTT1 deletion variants were genotyped by multiplex PCR assays. Allelic frequencies between the two groups were compared using a χ² test, and odds ratio (OR) with 95% confidence intervals were calculated. The results indicate that an excess of the GSTM1 null genotype was observed in cases compared with controls, 50% versus 33%. The genotypic frequency of GSTM1 null genotype between controls and patients was significantly different. This genotype confers an increased risk of NPC [OR = 2.18; CI 95% (1.23–5.33). The association between GSTM1 and increased NPC risk in this cases-controls study was present among both men [OR = 2.59; CI95% (1.81–4.32)] and smokers. No significant association was observed between null GSTT1 genotype and the risk of CNP.     

云南曲靖肺癌高发区氡气浓度与肺癌发病率的关系

目的:探讨肺癌高发区氡气浓度与肺癌发病率是否存在相关性.方法:采用中国辐射防护研究所生产的RLM-L型连续测氡仪,分别对处于宣威、富源肺癌高发区的7个农民肺癌家庭进行氡气监测.同期对宣威肺癌高发区的3个办公区、肺癌低发区的2个农民肺癌家庭以及曲靖麒麟区肺癌低发区的4个健康人口家庭共16个点进行氡气浓度监测.结果:宣威、富源肺癌高发区中6个点氡气浓度均远远超过国家环境标准的200 Bq/L,赋有"世界肺癌村"之称的来宾镇虎头村,其村北、村西、村南3个肺癌家庭氡气浓度也相对较高,但均小于200 Bq/L;其余7个监测点包括1个肺癌高发区、3个肺癌低发区的肺癌家庭以及麒麟区3个健康家庭氡气浓度均低于50 Bq/L.结论:宣威、富源不同地区氡气浓度与肺癌发病率存在一定相关性,氡气浓度高则肺癌发病率也高.宣威、富源肺癌高发病率除了与其特有的环境地理因素、遗传、基因易感性等相关外,也与氡气污染有关.     

Glutathione S-transferase M3 (A/A) genotype as a risk factor for oral cancer and leukoplakia among Indian tobacco smokers

Polymorphism in glutathione S-transferase (GST) genes, causing variations in enzyme activities, may influence susceptibility to oral cancer and leukoplakia in smokers and/or smokeless tobacco users. In this case-control study consisting of 109 leukoplakia and 256 oral cancer patients and 259 controls, genotype frequencies at GSTM1, GSTT1, GSTM3 and GSTP1 loci were determined by polymerase chain reaction-restriction fragment length polymorphism methods and analyzed by multiple logistic regression to determine the risks of the diseases. There were no significant differences in the distributions of GSTM1, GSTM3 and GSTT1 genotypes in patients and controls when all individuals were compared. In contrast, frequencies of ile/ile genotype at codon 105 and variant val-ala haplotype of GSTP1 was significantly higher (OR = 1.5; 95% CI = 1.0-2.0) and lower (OR = 1.4; 95% CI = 1.0-1.9) in oral cancer patients compare to controls, respectively. The impacts of all genotypes on risks of oral cancer and leukoplakia were also analyzed in patients with different tobacco habits and doses. Increased risks of cancer and leukoplakia were observed in tobacco smokers with GSTM3 (A/A) genotype (OR = 2.0, 95% CI = 1.0-4.0; OR = 2.0, 95% CI = 1.0-4.4, respectively). So, GSTM3 (A/A) genotype could become one of the markers to know which of the leukoplakia would be transformed into cancer. Heavy tobacco chewing (> 124 chewing-year) increased the risk of cancer in individuals with GSTT1 homozygous null genotype (OR = 3.0; 95% CI = 1.0-9.8). Furthermore, increased lifetime exposure to tobacco smoking (> 11.5 pack-year) increased the risk of leukoplakia in individuals with GSTM1 homozygous null genotype (OR = 2.4; 95% CI = 1.0-5.7). It may be suggested that polymorphisms in GSTP1, GSTM1, GSTM3 and GSTT1 genes regulate risk of cancer and leukoplakia differentially among different tobacco habituals.     

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms and lung cancer risk among Northwestern Mediterraneans

Several polymorphic genes including those encoding for glutathione S- transferases (GST) have been reported to be involved in modifying lung cancer risk in smokers. The gene GSTM1 is frequently deleted in humans and a possible association between the null genotype and lung cancer risk is controversial. Another polymorphic gene of the same supergene family, GSTT1, is also involved in the detoxification of some environmental carcinogens. Both genes were genotyped in (a) a group of lung cancer patients (n = 160); (b) a group of healthy smokers (n = 120); (c) a group of blood donors from the general population (n = 192). All patients and controls were Northwestern Mediterranean Caucasians. The results show that the GSTM1 null genotype (GSTM1*0/GSTM1*0) was slightly over represented in the lung cancer patients (frequency of 58%; OR: 1.40, 95% CI: 0.74-2.61, referred to healthy smokers). The histological type most clearly modified was small cell carcinoma (frequency of 62.2%, OR: 1.91, CI: 0.78-4.69). The subdivision of the patients with one or two copies of the GSTM1 gene according to a GSTM1*A, GSTM1*B or GSTM1*A/B genotype (frequencies of 28.2%, 11.2%, 2.5% respectively) revealed no significant differences between the cases and both control groups. The frequency of the deleted GSTT1 genotype among the lung cancer patients (24%) was not significantly increased (OR: 1.08, CI: 0.57-2.05, referred to healthy smokers). The results showed that 14.4% of the patients presented homozygous deletion of both GSTT1 and GSTM1 (12.5% among healthy smokers) suggesting no potentiation between null genotypes for lung cancer risk.      

Glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) polymorphisms and urothelial cancer risk with tobacco smoking.

The objective of this study was to examine the association between the genetic polymorphism of glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) genes and urothelial cancer risk in relation to smoking status. In this study, 325 Japanese patients with urothelial transitional cell carcinoma and 325 healthy controls were compared for frequencies of GSTM1, T1 and NAT2 genotypes. The frequencies of GSTM1 null genotype and NAT2 slow genotype were significantly higher in the cases than in the controls (adjusted odds ratio (OR) 1.37, 95% confidence interval (CI) 1.01-1.87, adjusted OR 3.09, 95% CI 1.69-5.63, individually). Furthermore, the risk of GSTM1 null genotype and NAT2 slow genotype was higher among smokers (adjusted OR 1.48, 95% CI 1.01-2.15, adjusted OR 4.28, 95% CI 1.96-9.36, individually). The regression analysis of cancer risk as a function of the amount of smoking showed that the susceptibility of people who had GSTM1 null genotype increased from 45 pack-years, while the susceptibility of people with NAT2 intermediate or slow genotype increased rapidly from 25 pack-years, compared with non-smokers. A multiplicative interaction between NAT2 intermediate or slow genotype and pack-years of smoking was found (P<0.001), but GSTM1 null genotype was not (P=0.06). Our results indicate that the GSTM1 null genotype and NAT2 intermediate or slow genotype are associated with an increased risk of urothelial cancer in relation to smoking amounts. Furthermore, the interaction between NAT2 intermediate or slow genotype and pack-years of smoking has a strong impact on urothelial cancer.