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。     

GSTM1和CYP1A1基因多态性与宫颈癌发生及发展的相关性

目的:探讨谷胱苷肽硫转移酶M1（GSTM1）和CYP1A1 Exon7基因多态性与宫颈癌发生发展的关系。方法:选取2013年5月至2015年5月我院收治的宫颈癌患者184例为宫颈癌组,203例进行体检的健康人群为参照组。用限制性片段长度多态性-聚合酶链反应（RFLP-PCR）检测所有受试者GSTM1和CYP1A1 Exon7基因型;记录无进展生存期（PFS）,并随访观察生存和死亡情况。结果:GSTM1分为野生型（wt）和突变缺失型（null）,CYP1A1 Exon7野生型为Ⅱe/Ⅱe,突变型包括突变纯合型（Val/Val）、突变杂合型（Ⅱe/Val）。宫颈癌组携带GSTM1突变型基因型比例与参照组间比较,差异无统计学意义（P＞0.05）;宫颈癌组携带CYP1A1 Exon7突变型基因型比例显著高于参照组（P＜0.05）,且携带突变型基因型个体患宫颈癌的风险是携带野生型基因型个体的2.333倍。GSTM1、CYP1A1 Exon7基因型与宫颈癌患者年龄、病理分期、肿瘤分化程度、肿瘤直径及淋巴结转移均无关（P＞0.05）,与患者病理类型有关（P＜0.05）。GSTM1、CYP1A1 Exon7突变型宫颈癌患者PFS中位数与野生型患者比较,差异均无统计学意义（P＞0.05）。GSTM1、CYP1A1 Exon7突变型宫颈癌患者基因型与宫颈癌患者预后无关（P＞0.05）。结论:GSTM1及CYP1A1 Exon7基因多态性是宫颈癌发生发展的危险因素,尤其是CYP1A1 Exon7突变型,为预防宫颈癌提供依据。     

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。     

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、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。     

CYP1A1与GSTM1的多态性与原发性肝癌遗传易感性的关系研究

目的：探讨细胞色素P4501A1（cytochorme P4501A1,CYP1A1)与谷胱苷肽S－转移酶M1(glutathione S-transferase M1,GSTM1)的多态性与原发性肝癌遗传易感性的关系。方法：应用等位特异PCR和多重PCR技术对52例原发性肝癌患者和100名健康对照的CYP1A1和GSTM1多态性进行分析。结果：肝癌患者CYP1A1第7外显子462Val的等位变异频率为0．46，显著高于正常对照的变异步率（0．22），病例组GSTM1的纯合型缺失频率（0．65），也显著高于对照组（0．41），携带有CYP1A1Val/Val纯合变异和GSTM1纯合缺失基因型的人患肝癌的风险大大增加，前者的比值比（odds ration,OR)及95％可信区间（confidence interval,95%CI)为4．13（1．28－13．35），后者的OR值及95％CI为2．72（1．35－5．46），二者联合OR值及95％CI为8．50（1．74－41．50）。结论：CYP1A1和GSTM1的多态是原发性肝癌的遗传易感因素，二者的等位变异增加了患肝癌的风险。     

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、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。     

CYP1A1和GSTM1基因多态性及其对个体肺癌易感性的联合效应:meta分析

背景与目的谷胱甘肽转移酶M1(glutathione S-transferase M1,GSTM1)和细胞色素P4501A1(cyto-chrome P450A1,CYP1A1)均存在基因多态性,并且对肺癌发病风险有一定的影响,两者联合作用对肺癌发病风险的影响尚无确切定论。本研究旨在探讨CYP1A1和GSTM1基因多态性及其联合效应与肺癌危险性的关系。方法在PubMed数据库、EMBASE数据库、中国生物医学文献数据库(china biology medicine,CBM)和中国知识基础设施工程数据库(china national knowledge infrastructure,CNKI)中查询文献,时间范围从各数据库建库至2011年3月。使用STATA10软件进行meta分析统计,对于每篇入选的文献均计算肺癌发生危险性调整混杂因素后优势比(odd ratio,OR)及其95%置信区间(confidence interval,CI)。结果 15篇文献最终被纳入本次研究。Meta分析显示GSTM1基因缺失时CYP1A1基因IIe/Val位点为纯合突变型时肺癌发病风险明显高于杂合型与纯合突变型联合,总体OR分别...     

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.     

GSTM1, GSTP1, CYP1A1 and CYP2D6 polymorphisms in lung cancer patients from an environmentally polluted region of Poland: correlation with lung DNA adduct levels.

The CYP and GST genetic polymorphisms, controlling metabolism of xenobiotics, are considered to influence an individual's susceptibility to environmental and occupational carcinogens and predisposition to cancer. In the study, the effect of the GSTM1, GSTP1, CYP1A1 and CYP2D6 polymorphisms was investigated in relation to PAH-DNA adduct levels in non-tumourous lung tissue from non-small cell lung cancer (NSCLC) patients living in the industrialized region of Upper Silesia, Poland. The level of adducts among smokers was significantly elevated when compared to non-smokers (P = 0.0005). Adduct levels correlated inversely with age of patients (P = 0.00001). The GSTP1 and CYP2D6 polymorphisms had no influence on DNA adduct levels. There was a significant relationship between high adduct levels and the combined GSTM1 (null)/CYP1A1-Ile/Val genotype in the squamous cell carcinoma group (P = 0.028). An elevated number of adducts was found in patients with the GSTM1 (null)/CYP1Al-Ile/Val genotype compared to the GSTM1 (null)/CYP1A1-Ile/Ile carriers (P = 0.043). A higher frequency of the CYP1A1-Ile/Val and GSTM1 (null)/CYP1A1-Ile/Val genotypes was observed in patients with high adduct levels (P = 0.05 and P = 0.009, respectively). A significant prevalence of the GSTM1(null)/CYP1A1-Ile/Val carriers in the adenocarcinoma group was found (P = 0.003). Thus, our findings imply that the GSTMI and CYP1A1 exon 7 polymorphisms may influence PAH-DNA adduct levels in target tissue from NSCLC patients, especially in the squamous cell carcinoma group. Moreover, individuals carrying the GSTM1(null)/CYP1A1-Ile/Val genotype might exhibit a greater predisposition to a peripheral type of lung cancer.     

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.     

CYPlA1、GSTMl基因多态性及环境因素与新疆哈萨克族食管癌家族聚集性的相关性研究

目的探讨CYPlAl、GSTMI基因多态性及环境因素与新疆哈萨克族食管癌家族聚集性发生的关系。方法通过检测86例新疆哈萨克族食管癌家族及82例对照家族外周血CYPlAl、GSTMl基因的多态性,并通过对环境危险因素进行现场问卷调查,探讨CYPlAl、GSTMI基因和环境因素在新疆哈萨克族食管癌家族聚集性中所起的作用。结果在新疆哈萨克族食管癌家族与对照家族之间cⅥ,1A1MspI、GSTMl不同基因型的分布频率差异均有统计学意义（P〈0．05）,MspI突变型和GSTMl缺失型之间交互作用显著增加食管癌家族集聚性,OR值为3．193（95％CI：1．645—3．376）,Logistic多因素分析显示新疆哈萨克族食管癌家族聚集性的发生与饮水情况、摄人较多新鲜蔬菜水果、CYPlAl基因MspI多态性等3个因素具有相关性,其中摄入较多新鲜蔬菜水果（OR=0。278,95％CI：0．137—0．551）是新疆哈萨克族食管癌家族聚集性的保护因素,饮用河水（OR=3．468,95％CI：1．562—6．551）、CYPlAI基因Mspl多态性的突变表型（OR=2．732,95％CI：1．741—3．886）是新疆哈萨克族食管癌家族聚集性的危险因素。结论CYPlAl、GSTMl基因多态性在新疆哈萨克族食管癌家族聚集性中起了一定的作用,饮用河水、CYPlAl基因Mspl突变表型是新疆哈萨克族食管癌家族聚集性的危险因素,可能与这些家族成员食管癌高发有关。     

CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis

Genetic polymorphisms of cytochrome p450 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes are thought to have significant effects on the metabolism of environmental carcinogens and thus on cancer risk, but the reported results are not always consistent. In this meta-analysis, we assessed reported studies of associations between polymorphisms of these two genes and risk of lung cancer in Chinese populations. Through a systematic literature search for publications between 1989 and 2006, we summarized the data from 46 studies on polymorphisms of MspI and exon7-Val of CYP1A1 and GSTM1 and lung cancer risk in Chinese populations, and found that compared with the wild-type homozygous genotype (type A), lung cancer risk for the combined variant genotypes (types B and C) was 1.34-fold (95% confidence interval [CI]=1.08-1.67) (Z=2.64, P=0.008); the risk for the combined variant genotypes (Ile/Val and Val/Val) of CYP1A1 exon7 was 1.61-fold (95% CI=1.24-2.08) (Z=3.62, P<0.001), compared with the Ile/Ile genotype; and that the risk for the GSTM1 null genotype was 1.54-fold (95% CI=1.31-1.80) (Z=5.32, P<0.001), compared with the GSTM1 present genotype. Therefore, in 46 published studies in Chinese populations, we found evidence of an association between the CYP1A1 variant and GSTM1 null genotypes and increased risk of lung cancer.     

红细胞补体受体1单核苷酸多态性与肝细胞癌发病风险的研究

目的 探讨红细胞补体受体1（CR1）单核苷酸多态性（SNP）与肝细胞癌（HCC）发病的关系。方法 收集102例HCC患者（HCC组）和98例健康体检者（对照组）的外周血样本,选取CR1的5个标签SNP位点（rs4844600 G＞A、rs17048010 T＞C、rs3818361 C＞T、rs11118167 T＞C和rs9429945 C＞T）进行检测,分析两组的红细胞CR1基因各SNP位点基因型、等位基因及单体型的分布差异及其与HCC患病风险的关系。同时按照性别、年龄相匹配的原则分别从对照组和HCC组中选取52例和53例样本采用流式细胞术检测其红细胞CR1的几何平均荧光强度比值（GMFIR）。结果 两组rs4844600 G＞A基因型和等位基因分布的差异有统计学意义（P＜0.01）。CR1基因rs4844600 G＞A／GG基因型携带者患HCC的风险为非携带者的2.458倍（95％ CI：1.357～4.451）,GA基因型携带者患病风险是非携带者的0.404倍（95％CI：0.218～0.746）,其等位基因G携带者患病风险为非携带者的1.945倍（95％CI：1.183～3.199）。rs17048010 T＞C、rs3818361 C＞T、rs11118167 T＞C、rs9429945 C＞T这4个SNP位点和rs11118167-rs3818361-rs17048010／TCT、TTC、CCT、TTT这4种单体型与HCC的患病风险无关（P＞0.05）。HCC组CR1的GMFIR水平为3.257±1.191,高于HCC组的2.652±0.789,差异有统计学意义（t=2.644,P=0.008）。结论 HCC患者红细胞免疫功能降低,CR1基因SNP位点rs4844600 G＞A与HCC发病关联。     

The association between glutathione S-transferase M1 genotype and polycyclic aromatic hydrocarbon-DNA adducts in breast tissue.

A major goal in molecular epidemiology is to identify preventable environmental risk factors and susceptible subpopulations. In a hospital-based molecular epidemiological case-control study of breast cancer, we investigated the relationship between DNA damage from exposure to polycyclic aromatic hydrocarbons (PAHs) and susceptibility attributable to inherited deletion of the xenobiotic detoxifying gene, glutathione S-transferase M1 (GSTM1). Prior to breast surgery, women (n = 227) were enrolled and interviewed and donated a blood sample. PAH-DNA adduct levels were measured by immunohistochemistry in breast tissue samples retrieved from pathology blocks, and GSTM1 genotype was determined by PCR using WBC DNA. The GSTM1 analysis included 95 cases and 87 benign breast disease controls. GSTM1 genotype was not associated with breast cancer case-control status (odds ratio = 0.73; 95% confidence interval, 0.37-1.44). However, the GSTM1 null genotype predicted PAH-DNA adduct levels in malignant (beta = 0.407; P = 0.003) and nonmalignant (beta = 0.243; P = 0.05) breast tissue from cases. This relationship was not seen in tissue from controls (beta = 0.095; P = 0.341). When tissue from controls was compared with tumor tissue from cases, there was a significant case-control difference in PAH-DNA adduct levels among women who were GSTM1 null. There was no such case-control difference among women who were homozygous or heterozygous for GSTM1. There was an interaction between GSTM1 and case-control status on adduct levels in breast tissue (P = 0.002). The results suggest that genetic susceptibility to the formation of PAH-DNA adducts in breast tissue may play a role in breast cancer development.     

Combined analysis of germline polymorphisms of p53, GSTM1, GSTT1, CYP1A1, and CYP2E1: relation to the incidence rate of cervical carcinoma

BACKGROUND: The authors established the genotype frequencies of cytochrome P450 (CYP1A1/MspI, CYP2E1/PstI, and CYP2E1/DraI), glutathione-S-transferase (GSTM1 and GSTT1), and p53 (exon 4/AcclI and intron 3/16-base pair duplication) gene polymorphisms in cervical carcinoma patients and controls and evaluated the association between the specific genotype or genotype combinations of these polymorphisms and the risk of cervical carcinoma. METHODS: In this case-control study, the genotypes of 181 human papillomavirus (HPV)-16 or HPV-18 positive cervical carcinoma patients and 1-to-1 age-matched controls were determined using a polymerase chain reaction-based technique. RESULTS: Among these polymorphisms, the individuals carrying arginine/proline genotypes of p53 showed a 9.5-fold increase of cervical carcinoma risk (95% confidence interval [CI], 4.9-18.6) compared with those individuals carrying arginine/arginine genotypes. The frequency of overall GSTT1 null genotypes also was significantly higher in cervical carcinoma patients compared with that of GSTT1 positive genotypes (P = 0.003; odds ratio [OR] = 1.9; 95% CI, 1.2-2.9). The genotype combination of p53 and GST played a more important role in describing the relative risk of cervical carcinoma. The individuals carrying both the arginine/proline genotype of p53 and the null genotype of GSTT1 showed a 3.5-fold increase of cervical carcinoma risk (95% CI, 1.8-7.1) compared with those individuals carrying both the arginine/arginine genotype of p53 and the GSTT1 positive genotype. In the patients who were stratified into the two age groups, the null genotypes of GSTT1 (69.1% vs. 45.5%; P = 0.016) and GSTM1 (61.8% vs. 40.0%; P = 0.028) in cervical carcinoma were significantly overrepresented in the younger age subgroup (age 40 years or younger) compared with those of controls. Especially in this age group, the individuals carrying both null genotypes of GSTT1 and GSTM1 showed a 17.8-fold increase of cervical carcinoma risk (95% CI, 2.2-141.0) compared with the individuals carrying both positive genotypes of GSTT1 and GSTM1. CONCLUSIONS: The results of the current study suggested that the arginine/proline genotype of p53, independently or in conjunction with the GSTT1 null genotype, could affect the genetic susceptibility for cervical carcinoma, and HPV positive women carrying both null genotypes of GSTT1 and GSTM1 have an increased risk of cervical carcinoma developing before age 40 years.     

广西扶绥县肝癌高发家系谷胱甘肽转硫酶GSTM1和GSTT1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。方法采用病例一对照研究方法,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（1）GSTM1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。（3）GSTM1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（1）GSTM1和GSTT1基因的多态性与肝癌家族聚集性相关;（2）GSTM1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。