CYP2E1,GSTM1基因多态性与甘肃地区食管癌易感性

目的探讨细胞色素氧化酶P450,GSTM1的基因多态性与甘肃地区食管癌遗传易感性之间的以及基因—基因的交互作用。方法运用病例对照分子流行病学研究方法和聚合酶链反应方法对食管癌病例组和正常对照组基因DNA进行CYP2E1,GSTM1基因分型。结果CYP2E1基因pst1多态性的三种基因型在食管癌组和对照组的频率差异有统计学意义（χ2=12.59,P〈0.05）。携带C1/C1基因型个体发生食管癌的风险是携带其他基因型2.80倍（OR=2.80,95%C I=1.21-6.46）。食管癌组GSTM1（-）基因型频率显著高于对照组（χ2=10.292,P〈0.05）,携带GSTM1（-）的个体患食管癌的危险性显著高于GSTM1（＋）基因型的个体（OR=2.337,95%C I=1.39-3.93）。联合分析CYP2E1基因pst1多态性和GSTM1基因多态性,携带有C1/C1和GSTM1（-）基因型的个体患食管癌的风险高于携带GSTM1（＋）和C1/C2或C2/C2基因型的个体（OR=3.00,95%C I=1.7375-5.182）。结论CYP2E1,GSTM1基因多态性与食管癌易感性有关联,CYP2E1基因C1/C1基因型是食管癌的易感性基因,而GSTM1基因缺失使食管癌危险性增加,CYP2E1,GSTM1存在交互作用。     

谷胱甘肽硫转移酶M1和T1基因多态性与燃煤型砷中毒发病的关系

目的探讨谷胱甘肽硫转移酶M1和T1（GSTM1、GSTT1）基因多态性与燃煤污染型砷中毒发病风险的关系。方法采用多重等位基因特异聚合酶链反应技术检测贵州省130名燃煤型砷中毒患者及140名健康个体的GSTM1和GSTT1基因多态性，并分析不同基因型与砷中毒发病的关系。结果砷中毒病例组和对照组GSTT1纯合缺失基因型（GSTT1^（-/-））的频率分别为58．5％和45．0％，组间比较差异有统计学意义（Х^2=6．246，P〈0．05）；携带GSTT1^（-/-）基因型个体发生砷中毒的风险是携带GSTT1非纯合缺失基因型（GSTT1^（＋/＋）or（-/-））个体的2．18倍[比值比（OR）adj=2．18，95％可信区间（CI）：1．183～4．018]。砷中毒病例组和对照组间GSTM1纯合缺失基因型（GSTM1^（-/-））频率的差异无统计学意义（P〉0．05）。基因型联合分析显示：携带GSTM1^（-/-）和GSTT1^（-/-）联合基因型的个体，其砷中毒的发病风险显著增加（ORadj=2．931，95％CI：1．024～8．387）。结论GSTT1^（-/-）基因型可能是燃煤型砷中毒发生的重要危险内因之一。     

细胞色素P450基因多态性与肺癌易感性的相关性分析

目的 探讨代谢活化酶细胞色素P4501A1（CYP1A1）、2D6（CYP2D6）、2E1（CYP2E1）和代谢解毒酶谷胱甘肽硫转移酶（GSTM1）与肺癌易感性的关系。方法采用PCR、PCR—RFLP技术检测原发性肺癌组（279例）及对照组（684例）的CYPlAI、CYP2D6、CYP2E1、GSTM1代谢酶基因型，对不同基因型在两组分布频率的差异进行OR值的统计分析。结果CYPlAl突变等位基因（m）、GSTMl功能缺失型（-）分别可使患肺癌的危险性增加1．64（OR=1．64，95％CI为1．21—2．22，P=0．001）和1．58倍（oR=1．58，95％CI为1，19—2．11，P=0．002）。其中CYPlAl与肺鳞癌、小细胞癌，GSTMl与肺鳞癌及肺腺癌明显相关（均P〈0．05）。同时携带GSTMI（-）和CYPlAl（m）可使患肺癌的危险性明显增加（OR=2．75，95％CI为1．73～4．39，P=O．OOO）。在重度吸烟人群携带GSTMl（-）、CYPlAl（m）、CYP2D6（W）或CYP2ElA基因型均可使患肺癌的危险性显著增加5．71—11．67倍（辟O．000）。结论携带GSTMI（-）及CYPlAl（m）等位基因型者患肺癌的危险性上升，二者有协同作用。在重度吸烟人群，CYP及GSTMl的检测有利于发现肺癌的高危人群。     

DNA修复基因XRCC3多态性与肺癌易感性的关系

目的 研究DNA修复基因XRCC3多态性与肺癌易感性的关系。方法采用病例一对照研究，于2006年9月至2007年1月收集上海肺科医院原发性肺癌患者291例及同期住院的非肿瘤患者273例，应用Taqman探针结合实时荧光PCR方法分析病例组和对照组XRCC3基因Thr241Met的多态性分布，比较不同基因型与肺癌易感性的关系以及基因多态性与吸烟对肺癌的交互作用。对照组与病例组的比较用X。检验，以调整比值比及95％可信区间表示相对危险度，所有统计检验均为双侧概率检验，所有资料均用SPSS软件进行统计。结果与携带XRCC3密码子241野生纯合基因型（Thr／Thr）且不吸烟者相比，携带同样基因型且吸烟者患肺癌的风险会增加，其调整比值比（OR值）为2．47[95％可信区间（CI）为1．49-4，08，P〈0．01]；携带有杂合基因型（Thr／Met）且吸烟者患肺癌的风险也会增加，其调整OR值为2．28（95％CI为1．21-6．60，P=0，017）。野生纯合基因型（Thr／Thr）且吸烟量少于30包年可能对肺腺癌有较弱的保护作用（OR=0．49，95％CI为0．26-0．93，P=0，03）。携带有XRCC3密码子241Met等位基因且吸烟者患肺鳞癌的风险明显增加（调整OR=9．69，95％CI为3．27-28．72，P〈0．01）。携带241Met等位基因且吸烟剂量〈30包年和≥30包年的患者患肺鳞癌的风险也不同，OR值分别为8，00（95％CI为1．97-32．52，P〈0．01）和11．67（95％CI为2．98～45．73，P〈0．01）。结论DNA修复基因XRCC3多态性可能对肺癌易感性产生影响，并可能与吸烟有一定的协同作用。     

ABCA1基因多态性与冠心病易感性的关联研究

目的探讨三磷酸腺苷结合盒转运子A1（ATP binding cassette transporter1,ABCA1）基因R219K及M883I单核苷酸多态性（SNP）位点与脂代谢和冠心病（coronary heart disease,CHD）易感性的关系。方法以医院为基础的病例-对照研究。经冠状动脉造影确诊的冠心病病例224例,同一地区正常对照248例。分别以PCR-RFLP和PIRA-PCR对ABCA1第219密码子G→A（Arg219Lys）和第883G→A（Met883Ile）密码子多态进行检测,比较不同基因型与个体血脂水平和冠心病患病风险的关系。结果吸烟、高血压和高血糖是冠心病的独立危险因素。与携带219RR基因型者比较,携带至少1个219K等位基因者（即RK和KK基因型）冠心病患病风险显著降低59％（OR = 0．41,95％ CI = 0．27～0．61）。而在883位点,II基因型携带者患冠心病率较低（OR = 0．54,95％ CI = 0．26～1．11）。而两位点联合作用分析发现与携带219RR,883MM或883MI基因型者相比较,携带其他组合基因型的个体冠心病患病风险降低61％（OR = 0．39,95％ CI = 0．26～0．60）。另外,对照组中携带219K等位基因者血清HDL-C水平显著高于219K非携带者（P = 0．037）,提示Arg219Lys位点的多态改变主要通过改变HDL-C水平影响个体冠心病的患病风险。结论ABCA1 R219K可能与中国汉族人群冠心病遗传易感性有关,血清高密度脂蛋白可能是其作用靶点。     

GSTM1基因多态性与肺癌发病的相关性研究

目的探讨谷胱甘肽硫转移酶M1（GSTM1）基因多态性与肺癌易感性的关系，以期用于肺癌的筛检。方法用PCR法分析56例肺癌（简称肺癌组）和42例健康对照组GSTM1基因型，并用Logistic多因素回归法分析可能影响GSTM1的职业环境因素、生活习惯、及宿主个体因素。结果肺癌组GsTM1基因缺失型[GSTM1（-）]发生率达71．43％，显著高于对照组的45．24％，差异有统计学意义，P〈0．05；GSTM1（-）型与肺癌呈高度联系强度，OR=3．09（95％CI=1．32～6．94）；Logistic回归分析表明，职业接触PAHs（OR=6．6939，P=0．009）、吸烟（OR=9．7058，P=0．0010）、既往肺病史（OR=7．5233，P=0．0465）与GST M1（-）型相关。结论GST M1（-）型个体增加了肺癌发生的风险性，可作为宿主肺癌易感性的遗传标志。     

代谢酶基因CYP 1A1与广西胃癌遗传易感性的关系

目的探讨代谢酶基因CYP 1A1MSP1多态性与广西地区汉族、壮族人群胃癌遗传易感性之间相关性。方法采用PCR-RFLP技术检测广西地区汉族、壮族人群中121例胃癌患者和138例健康人CYP1A1MSP1多态性的分布频率,分析其与广西地区汉族、壮族人群胃癌遗传易感性的相关性及与吸烟、饮酒在胃癌易感性中的相互作用。结果 (1)CYP 1A1MSP1三种基因型(m1/m1、m1/m2、m2/m2)分布频率在两组间比较差异无统计学意义(χ2=0.901,P=0.342);(2)携带CYP1A1MSP1突变m2基因型的个体较携带m1/m1基因型的个体患胃癌的风险增加(OR=1.509),但差异无统计学意义(P=0.342)。结论单独的CYP 1A1基因MSP1多态性与广西地区汉族、壮族人群胃癌易感性无明显相关性。     

青海地区藏族人群着色性干皮病基因D、谷胱甘肽-S-转移酶M1基因多态性与肝癌易感性的关系

目的 探讨青海地区藏族人群着色性干皮病基因D(XPD)、谷胱甘肽-S-转移酶(GST)M1基因多态性与原发性肝癌(PHC)易感性的关系. 方法 采用病例对照研究,选择青海地区藏族PHC患者及同期藏族健康体检者各102例,用PCR、变性高效液相色谱技术进行基因分型检测,以非条件logistic逐步回归模型进行PHC危险因素的多变量分析,比较不同基因型与PHC患病风险的关系.计数资料采用x2检验,以比值比(OR)及其95％可信区间(CI)表示相对危险度. 结果 吸烟、肉食、饮酒、HBV感染、直系亲属HBV感染、直系亲属肝癌等均进入logistic回归模型(α=0.05).XPD751C突变基因型在病例组和对照组的分布频率分别为21.6％和10.8％,组间差异有统计学意义(x2=4.374,P=0.036),罹患PHC的风险OR为2.275(95％CI为1.04～4.98).GSTM1空白基因型在病例组和对照组的分布频率分别为60.8％和44.1％,组间差异有统计学意义(x2=5.680,P=0.017);携带GSTM1空白基因型者患病风险是携带GSTM1非空白基因型者的1.963倍(95％ CI为1.124 ～ 3.428).将XPD751C基因突变和GSTM1空白联合基因型作为暴露因素,罹患肝癌的风险OR为3.030 (95％ CI为1.165 ～ 7.881);XPD751C突变基因型与HBV感染、饮酒、家族直系亲属肝癌等因素有交互作用.结论 吸烟、饮酒、肉食、HBV感染、直系亲属HBV感染、直系亲属患肝癌等是青海藏族人群罹患PHC的主要环境危险因素;XPD751C突变等位基因型、GSTM1空白基因型是青海藏族人群PHC的易感因素;携带XPD751C突变和GSTM1空白联合基因型的个体,比单个基因型患病风险显著增加;青海藏族人群携带XPD751C突变等位基因型的个体可分别与HBV感染、饮酒、家族直系亲属肝癌3种环境危险因素共同诱导PHC的发生.     

E-选择素S128R基因型与糖尿病肾病的相关性

目的探讨E-选择素基因S128R多态性各等位基因及基因型在桂北地区汉族糖尿病肾病（DN）患者中的分布频率,并分析其基因型与DN的相关性。方法采用PCR—RFLP方法检测205例DN患者（DN组）及198例健康查体者（对照组）的S128R基因型,同时检测两组相关的生化指标水平。结果DN组FPG、HbA1、TG、TC、BUN、Cr等高于对照组（P〈0．05）,两组S128R基因型分布具有统计学差异（X^2=7．37,P〈0．05）;RR基因型患DN的风险为ss基因型的2．34倍（OR=2．34,95％CI：1．91～2．86）;两组s等位基因和R等位基因频率有统计学差异（X^2=14．73,P〈0．05,OR=2．34,95％CI：1．50～3．65）,携带R等位基因的DN患者相关实验室指标水平明显高于不携带R等位基因者。结论E-选择素S128R基因多态性与DN的发病有关,其中R等位基因可能是广西桂北地区汉族人DN发病的遗传易感基因,携带R等位基因的个体可能通过影响血糖、血脂的代谢而增加DN的发病风险。     

云南哈尼族彝族幽门螺杆菌感染人群胃癌易感基因研究

胃癌的发生是生物、环境、宿主等因素共同作用的结果．宿主遗传因素与幽门螺杆菌（H．pylori）感染后的不同临床结局有关。目的：筛选云南红河州哈尼族彝族Hpylori感染人群的胃癌易感基因,探讨不同基因型和等位基因与H．pylori感染宿主胃癌发病风险的相关性。方法：通过PubMed、CNKI和HapMap数据筛选出12个中国人群胃癌易感相关单核苷酸多态性（SNP）位点,以芯片技术对哈尼族彝族H．pylori感染慢性胃炎和胃癌患者的这些SNP位点进行分型。结果：IL-1β-3IC／T和IL-1β-511C/T位点存在完全连锁不平衡．其基因型（P=0．014）和等位基因频率（P=0．049）在胃癌和胃炎组中有显著差异,-511CT／-31CT（OR=2．256,95％CI：1．048～4．855）和-511TT/-31CC（OR=3．312,95％CI：1．462～7．502）基因型胃癌发病风险显著高于-511CC／-31TT基因型。COX-2．899C／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．033）,GG基因型胃癌发病风险显著高于CG基因型（OR=2．796,95％CI：1．053～7．423）。TNF—α-238A／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．037）．AA、AG基因型胃癌发病风险显著高于GG基因型（OR=2．600．95％CI：1．130～5．985）。结论：IL-1β-31C、IL-1β-511T等位基因和COX-2—899GG基因型可增高云南红河州哈尼族彝族Hpylori感染人群的胃癌发病风险,TNF-α-238GG基因型对上述人群的胃癌发生具有保护作用。     

Genetic susceptibility and environmental factors of esophageal cancer in Xi＇an

AIM: To analyse the role of genetic susceptibility and environmental factors in the process of esophageal cancer (EC) formation in Xi‘an, China. METHODS: A hospital based case-control study, combined with molecular epidemiological method, was carded out. A total of 127 EC cases and 101 controls were interviewed with questionnaires containing demographic items, habit of tobacco smoking, alcohol drinking, and family history of EC. Polymorphism of CYPIA1 and GSTM1 of 127 EC cases and 101 controls were detected by PCR method. The interactions between genetic susceptibility and environmental factors were also discussed. RESULTS: Tobacco smoking, alcohol drinking and a family history of EC were risk factors for EC with an OR of 2.04 (95% CI 1.15-3.60), 3.45(95% CI 1.74-6.91), 3.14 (95% CI 1.28-7.94), respectively. Individuals carrying CYP1A1 Val/Val genotype compared to those with CYP1A1 Ile/Ile genotype had an increased risk for EC (OR 3.35, 95% CI 1.49-7.61). GSTM1 deletion genotype was a risk factor for EC (OR1.81, 95% CI 1.03-3.18). Gene-environment interaction analysis showed that CYPIA1 Val/Val genotype, GSTM1 deletion genotype had synergetic interactions with tobacco smoking, alcohol drinking and family history of EC. CONCLUSION: Tobacco smoking, alcohol drinking and a family history of EC are risk factors for EC. CYP1A1 Val/Val and GSTM1 deletion genotypes are genetic susceptibility biomarkers for EC. There are synergic interactions between genetic susceptibility and environmental factors.     

基因多态性及常见危险因素与胃癌易患性的研究

目的探讨中国汉族人群细胞色素P450(CYP)1A1基因型、谷胱甘肽巯基转移酶(GST) M1基因型及常见危险因素与胃癌易患性的关系,为胃癌高危人群的确定和胃癌的一级预防提供分子生物学手段。方法所有研究对象经胃镜和病理检查分为胃癌(GC,仅包括胃腺癌)组102例、慢性萎缩性胃炎(CAG)组110例、慢性浅表性胃炎(CSG)组110例、胃溃疡(GU)组62例、十二指肠溃疡(DU)组62例及正常对照组62例。采用统一的调查表对每个研究对象进行调查,调查项目包括年龄、性别、学历、职业、吸炯史、饮酒史、饮食习惯、肿瘤家族史等。采用序列特异性引物的聚合酶链反应(PCR-SSP)方法检测CYP1A1基因型及GSTM1基因型测定组的基因型频率,ELISA法测定幽门螺杆菌(Hp)感染,病例对照研究方法进行流行病学分析。结果单因素分析显示与胃癌有关联的危险因素为年龄、性别、文化程度、职业、Hp感染、吸烟、CYP1A1 G/G基因型、GSTM1空白基因型,其中大蒜为保护性因素;多因素分析显示与胃癌有关联的危险因素分别为Hp感染、CYP1A1 G/G基因型、GSTM1空白基因型,大蒜仍为保护性因素。CYP1A1 G／G基因型及GSTM1空白基因型对胃癌的发生具有协同作用。Hp感染与CYP1A1 G／G基因型、GSTM1空白基因型对胃癌的发生存在协同作用;吸烟与CYP1A1 G/G基因型、GSTM1空白基因型存在协同作用。结论具有CYP1A1 G/G或GSTM1基因型的个体发生胃癌的危险性增加,而同时有两种基因型的个体发生胃癌的危险性更高,这两种基因型可以认为是胃癌易患性的标志。     

细胞色素P4501A1基因多态性和谷胱甘肽硫转移酶基因缺失及烹调油烟暴露与非吸烟女性肺癌易感性的关系

目的 探讨细胞色素P4501 A1(CYP1A1)MspI位点多态性、谷胱甘肽硫转移酶(GSTM1)基因缺失及烹调油烟暴露与非吸烟女性肺癌易感性的关系.方法 2009年3一12月选择中南大学湘雅医院女性非吸烟的原发性肺癌患者及对照各160例,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)及聚合酶链反应(PCR)技术分别检测CYP1A1 MspI多态性及GSTM1基因型,分析基因的多态性、分型及烹调油烟暴露与肺癌遗传易感性的关系.结果 肺癌组及对照组烹调油烟暴露的频率分别为51.9%(83例)及33.7%(54例),差异有统计学意义(x2=10.734,P＜0.01);肺癌组MspI位点突变的等位基因频率为44.4%(71例),高于对照组(36.9%,59例),差异无统计学意义(X2=3.731,P＞0.05);携带突变型或杂合型基因同时又有油烟暴露个体患肺癌的风险明显增高,OR(odds ratio)值分别为3.032(95%CI为1.291～7.124)和2.769(95%CI为1.341～5.552);肺癌组GSTM1缺失型的频率为58.1%(93例),与对照组(45.0%,72例)比较,差异有统计学意义(X2=0.518,P＜0.05),GSTM1缺失型的个体患肺癌的风险明显增高,OR值为1.697(95%CI为1.090～2.640);携带GSTM1缺失型且有烹调油烟暴露的个体肺癌的易感性明显增加,其OR值为3.617(95%CI为1.899～6.891);GSTM1缺失型与CYP1A1 MspI杂合型或突变型联合作用时,个体患肺癌的风险亦增高,OR值分别为1.966(95%CI为1.007～3.836)和2.402(95%CI为1.023～5.640),差异明显.结论 烹调油烟暴露是非吸烟女性肺癌的危险因素;CYP1A1 MspI基因多态性与烹调油烟联合作用可增加肺癌发病的风险;GSTM1基因缺失可能是非吸烟女性肺癌的遗传易感因素,其与烹调油烟暴露联合作用可明显增加肺癌发病的风险,且GSTM1基因缺失与CYP1A1基因多态性存在交互作用.     

CYP1A1, GST gene polymorphisms and risk of chronic myeloid leukemia

PRINCIPLES: Associations between polymorphisms for genes encoding enzymes involved in biotransformation of xenobiotics and susceptibility to several cancers have been shown in several studies. The aim of the present study is to investigate the influence of cytochromes P450 (CYP450) 1A1*2C and Glutathione S-transferases (GSTs) (T1 and M1) gene polymorphisms in susceptibility to chronic myeloid leukaemia (CML). METHODS: The frequency of CYP1A1 Ile/Val alleles and of GSTT1 and GSTM1 homozygous deletions was examined in 107 patients with CML and 132 healthy controls by PCR and/or PCRRFLP methods using blood samples. RESULTS: The frequency of CYP1A1 Val allele was found to be 19.2% in CML patients and 4.4% for controls, indicating that persons carrying this allele had an increased risk of CML (OR = 5.10, 95% CI: 2.60-9.97). The frequency of individuals carrying the GSTT1 null genotype was higher among CML patients (40.2%) compared to controls (19.2%) (OR = 2.82, 95% CI: 1.58-5.05; p <0.001). Therefore, GSTT1 present genotype may be a protective factor for CML. Although GSTM1 null genotype frequency was slightly higher in the patient group (44.9%) than in the controls (42.3%), this difference was not statistically significant (OR = 1.11, 95% CI: 0.66-1.86; p = 0.693). Individuals with GSTM1 null genotypes without the T allele have a 5.981 higher risk for CML than those who have the T allele. CONCLUSIONS: This data suggests that polymorphic CYP1A1 and GSTT1 genes appear to affect susceptibility to CML.     

Glutathione-S-transferase （GSTM1, GSTrl） and the risk of gastrointestinal cancer in a Korean population

AIM: To evaluate the association of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population.METHODS: We conducted a population-based, large-scale case-control study including 2213 GCs, 1829 CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSTT1 were determined using real-time PCR.RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls. Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer.CONCLUSION: GSTM1 and GSTT1 null genotypes were not associated with increased risk of GC or CRC in Koreans.     

Glutathione-S-transferase (GSTM1, GSTT1) and the risk of gastrointestinal cancer in a Korean population

AIM: To evaluate the association of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population.METHODS: We conducted a population-based, largescale case-control study including 2213 GCs, 1829CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSTT1 were determined using realtime PCR.RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls.Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer.CONCLUSION: GSTM1 and GSTT1 null genotypes were not associated with increased risk of GC or CRC in Koreans.     

Combined GSTM1 and GSTT1 null genotypes are associated with a lower risk of papillary thyroid cancer

Individual susceptibility to cancer is influenced by polymorphisms of genes encoding drug-metabolizing enzymes such as the glutathione S-transferases (GST). The null polymorphisms of the GSTM1 and GSTT1 genes have been associated to a modified risk of several cancers but studies of thyroid cancer have produced conflicting results. The aim of this study was to investigate the relationship between these polymorphisms and the risk of papillary thyroid cancer (PTC). A total of 188 patients with PTC and 247 controls were genotyped using a PCR-based assay. Odds ratios (OR) and 95% confidence intervals (CI) for each homozygous null genotype were determined. The frequency of each of the GSTM1 and GSTT1 null genotypes did not differ significantly between patients and controls (OR=0.83, 95%CI: 0.56-1.21; p=0.328; and OR=0.66, 95%CI: 0.39-1.12; p=0.123, respectively), but the frequency of individuals that had the combined GSTM1 null/GSTT1 null genotypes was significantly lower in the patient group (OR=0.50, 95%CI: 0.26-0.97; p=0.040). The GSTM1 null genotype was associated with a lower risk of advanced cancer stages (III/IV) (OR=0.50, 95%CI: 0.26-0.96; p=0.036) and the GSTT1 null genotype was associated with a lower risk of the follicular variant of PTC (OR=0.31, 95%CI: 0.10-0.97; p=0.044). These results suggest that GSTM1 and GSTT1 null genotypes are weak, yet possible, modifiers of the risk of PTC. This protective effect may be due to a role of the GSTM1 and GSTT1 encoded enzymes in the metabolic activation of putative thyroid carcinogens or in other pathways involved in thyroid carcinogenesis.     

Polymorphisms at GSTM1 and GSTT1 gene loci and susceptibility to cervical cancer in Indian population

Multiple allelism at loci encoding detoxifying enzymes is associated with cancer risk. Glutathione S-transferase (GSTs) catalyzes the conjugation of glutathione to numerous potentially genotoxic compounds. This study evaluates the influence of genetic polymorphisms of GST M1 and GST T1 on susceptibility to cervical cancer. A multiplex polymerase chain reaction method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA isolated from cases with cervical cancer (n=142) and normal controls (n=96). The results showed that the frequency of homozygous GSTM1 null genotype was higher in cervical cancer cases (57.0%) as compared to controls (34.4%) and the differences were significant (p<0.05), OR=2.5, 95% CI: 1.4--4.5. The frequency of homozygous GSTT1 null genotype in cancer cases was 19.7% in comparison to 12.5% in controls, however, the difference was not statistically significant (OR=1.7, 95% CI: 0.8-3.8). Significant difference was found between the cases and controls in the distribution of the null genotype of GST M1 in individuals aged above 45 years (p=0.04), but this difference was not significant in individuals aged below 45 years (p=0.06). No significant differences were found in cervical cancer cases and controls when data were analyzed according to age group for GSTT1 null genotype. Further, the combined analysis of both GSTM1 null and GSTT1 null genotypes did not appear to influence the susceptibility to cervical cancer, suggesting that polymorphisms of other detoxifying enzymes may play a significant role in cervical carcinogenesis.     

Genetic polymorphism at GSTM1 and GSTT1 gene loci and susceptibility to oral cancer

GSTs are phase II enzymes which are involved in the detoxification of active metabolites of many potential carcinogens from tobacco smoke and therefore may play an important role in modulating susceptibility to tobacco related cancers. This study evaluates the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci on susceptibility to oral cancer. The genotyping was based on multiplex PCR assay that identified the GSTM1 and GSTT1 null (-/-) genotypes but didn't distinguish homozygous wild type+/+ and heterozygous +/- individuals. Genomic DNA was isolated from cases with oral cancer (n=40) and normal controls (n=87). The prevalence of the GSTM1 null genotypes was 29/87 (33.3%) and 21/40 (52.5%) in controls and oral cancer cases, respectively but the differences were not significant (OR=2.2; 95%CI=0.96-5.1; p=0.06). The frequency of homozygous GSTT1 null genotype in cancer cases was 17/40 (42.5%) as compared to 13/87 (14.94%) in controls and the differences were highly significant (OR=4.2; 95%CI=1.64-10.9; p=0.0002). Oral cancer cases had higher proportion of both GSTM1 and GSTT1 null genotypes as compared to controls but the differences were not statistically significant (OR=2.9; 95%CI=0.71-11.9; p=0.17). When individuals were categorized into two groups, no differences were observed for GSTM1 null genotype frequencies in control and cancer cases (OR=2.9; 95%CI=0.9-9.6; p=0.08) (OR=1.6; 95%CI=0.44-6.1; p=0.58) in <=50 yrs and >50 yrs of age groups. Significant differences between control and cancer cases were observed for GSTT1 null genotypes both in <=50 yrs and >50 yrs of age groups (OR=4.0; 95%CI=1.1-15.0; p=0.03) (OR=4.5; 95%CI=0.97-22.29; p=0.05), respectively. The effect of smoking on GSTM1 null individuals was not found significant (OR=1.0; 95%CI=0.19-4.86; p=0.75) but it was significant in case of GSTT1 null individuals (OR=6.33; 95%CI=1.0-44.1; p=0.02). Our results thus suggest that GSTT1 gene polymorphisms modulate susceptibility to tobacco-related cancer of the oral cavity.