谷胱甘肽硫转移酶Mul—1（GSTM1）基因多态性与肺癌易感性关系的研究

目的　探讨中国汉族广东人群中谷胱甘肽硫转移酶 Mul- 1(GSTM1)基因缺失及吸烟与肺癌易感性的关系。　方法　采用病例 -对照研究方法 ,应用 PCR技术检测 91例肺癌患者、138例对照的 GSTM1基因多态性。　结果　GSTM1基因缺失在肺癌组和对照组中的频率分别为 6 1.5 %和 5 2 .9% ,OR=1.38(0 .80～ 2 .38)差异无统计学意义 (P>0 .0 5 ) ,与吸烟联合分析时发现 GSTM1基因缺失的 OR值为 3.0 7,比单纯吸烟对肺癌的 OR值 (1.87)大 (P<0 .0 1)。　结论　 GSTM1基因缺失与吸烟可能协同增加患肺癌的危险性     

GSTM1基因多态性与肺癌易感性的病例对照研究

[目的]探讨谷胱甘肽硫转移酶μ基因(GSTM1)缺失和吸烟、饮酒与肺癌易感性的关系。[方法]采用病例对照研究方法,调查42例病例和103例对照的吸烟、饮酒习惯,应用PCR技术检测GSTM1的基因型。采用lo-gistic回归分析GSTM1基因型与肺癌的关系及其与吸烟量、饮酒的交互作用。[结果]病例组GSTM1缺失率57.1%,对照组55.3%,两组差异无统计学意义,经调整混杂因素后,GSTM1缺失联合重度吸烟(累计吸烟量≥30包×年)的OR值12.841(2.322～71.008),交互作用系数为2.796。GSTM1联合饮酒的OR值10.728(1.270～90.656),交互作用系数为1.651。[结论]GSTM1基因缺失与重度吸烟(累计吸烟量≥30包×年),GSTM1基因缺失与饮酒均对肺癌的发生具有交互作用。     

肺癌患者及一级亲属GSTM1基因型分析

目的通过检测肺癌患者及其一级亲属谷胱甘肽转硫酶M1(GSTM1)基因型,探讨GSTM1基因作为肺癌遗传易感性标志物的意义。方法采用基于家庭和医院病例的病例对照研究方法,应用双重PCR方法检测其GSTM1基因型。结果肺癌组GSTM1基因缺失率为71.43%(45/63),肺癌亲属组为74.19%(46/62),住院对照组为53.33%(16/30),健康体检组为51.06%(24/47)。肺癌组、肺癌亲属组GSTM1基因缺失率均显著高于健康对照组(P=0.03和0.01);与健康体检组相比肺癌组的OR为2.4(95%CI=1.09～5.29):肺癌亲属组的OR为2.76(95%CI=1.23～6.180)。肺癌亲属组的GSTM1基因缺失率也显著高于住院对照组(P<0.05),OR为2.51(95%CI=1.01～6.24)。对肺癌病人及非病人吸烟、GSTM1基因缺失因素进行叉生分析,吸烟与GSTM1基因缺失对肺癌发生的危险有协同作用。结论GSTM1基因可作为肺癌遗传易感性标志物。     

GSTM1、GSTT1基因缺失与肺癌遗传易感性关系的研究

目的　探讨GSTM1、GSTT1基因缺失与肺癌发病之间的关系。方法　采用PCR技术检测 77例肺癌患者和 10 7例健康对照人群中GSTM1、GSTT1基因缺失的频率。结果　病例组GSTM1基因缺失的频率为5 8 4 % ,显著高于对照组的缺失频率 4 2 1% (χ2 =4 811,P =0 0 2 8) ,危险度分析得出OR =1 938,95 %CI为1 0 70～ 3 5 0 9;病例组GSTT1基因缺失的频率为 5 7 1% ,接近对照组 5 0 5 %的水平 (χ2 =0 80 2 ,P =0 371)。联合分析表明两基因在肺癌发生中具有协同作用。结论　GSTM1基因缺失或GSTM1、GSTT1基因联合缺失可能与肺癌的发生有关     

细胞色素P450基因1A1与肺癌类型病例对照研究

目的研究肿瘤易感性标记物细胞色素P4501A1（CYP1A1）与肺癌类型的关系。方法收集原发性肺癌91例和138例对照。所有研究对象均采血进行DNA提取，采用多聚合酶链反应-限制性片段长度多态性（PCR-RELP）技术检测CYP1A1基因型。结果鳞癌与CYP1A1突变型有关（OR=2．72，P=0．011）。吸烟与CYP1A1基因的联合作用未发现与不同类型肺癌有关系。对不吸烟者，CYP1A1杂合型可能是一个保护因素（OR=0．13，P=0．033），降低其发生鳞癌的危险性。饮酒和CYP1A1突变型基因联合作用与鳞癌有关（OR=4．32，P=0．048），和CYP1A1杂合型基因联合作用与腺癌有关（OR=22．00，P=0．009）。结论CYP1A1突变型基因型是肺癌的易感因素。     

CYP1A1和GSTM3基因多态性与肺癌易感性关系

目的 研究CYP1 A1 Exon7和GSTM3基因多态性与内蒙古地区汉族肺癌易感性的关系.方法 采用等位基因特异性扩增法(ASA)和限制性片断长度多态性(PCR-RFLP)技术对324例汉族非肺部疾病患者和174例汉族肺癌患者进行CYP1A1 Exon7及GSTM3基因多态性分析;同时研究其与吸烟及肺癌之间的相互关系.结果 肺癌组与对照组的CYP1 A1 Exon7、GSTM3基因多态性差异均无统计学意义(P＞0.05);吸烟人群患肺癌的危险性是不吸烟人群的2.107倍(OR=2.107,95％ CI=1.44～3.080);携带CYP1A1 Exon7基因突变纯合型(Val/Val)的个体患肺癌风险增高(OR=1.576);携带CYP1 A1 Exon7基因突变杂合型和突变纯合型(Ile/Val+ Val/Val)并且吸烟的个体患肺癌的风险增高(OR=2.503).结论 吸烟为肺癌的易感因素,CYP1A1 Exon7基因突变杂合型和突变纯合型是肺癌的可疑易感因素,和吸烟在肺癌易感性方面具有协同作用;GSTM3基因多态性与肺癌易感性无关.     

GSTM1、GSTT1基因缺失与肺癌易感性的关系

目的探讨谷胱苷肽S转移酶M1（GSTM1）、谷胱苷肽S转移酶T1（GSTT1）基因缺失与肺癌发病之间的关系及其与P16表达降低的相关性在肺癌发生中的作用。方法采用PCR技术检测77例肺癌患者和107例健康对照人群中GSTM1、GSTT1基因缺失的频率，以十二烷基磺酸钠（SDS）-聚丙烯酰胺凝胶电泳及蛋白印迹（WeStern—blot）技术测定P16蛋白在正常组织中的表达。结果病例组GSTM1基因缺失频率为58．4％，显著高于对照组缺失频率为42．1％（X^2=4．811，P=0．028），危险度分析OR=1．938，95％CI=1．070～3．509；病例组GSTT1基因缺失频率为57．1％，接近对照组50．5％缺失频率的水平（X^2=0．802，P=0．371）。联合分析表明，2种基因在肺癌发生中具有协同作用。GSTM1空白基因型与GSTM1非空白基因型个体相比、GSTM1／GSTT1联合空白基因型与其他联合多态基因型相比P16表达水平降低，差异有统计学意义（P〈0．05）。结论GSTM1基因缺失或GSTM1、GSTT1基因联合缺失在肺癌患者中发生频率增高，可增加个体患肺癌的易感性；GSTM1基因缺失及GSTM1／GSTT1联合缺失可能与抑癌基因p16的蛋白表达减低有关。     

CYP1A1和GSTM1基因多态与肺癌发病关系的病例-对照研究

目的 探讨肺癌易感性标记物CYP1A1及GSTM1基因多态以及吸烟等其他环境暴露因素与肺癌发生的关系。方法 采用病例-对照研究的方法，收集原发性肺癌病例91例以及非肺部疾患的住院病例(对照)91例，所有的研究对象均采静脉血进行DNA抽提，并用PCR方法检测CYP1A1以及GSTM1基因多态，同时调查研究对象吸烟等其他环境暴露因素。应用Logistic回归分析方法进行单因素和多因素的分析。结果 无论是单因素分析还是多因素分析均未显示出CYP1A1和GSTM1基因多态与肺癌发病的关联。多因素分析结果表明：化程度的OR为0．63(95％CI：0．45～0．86)，吸烟量的OR为1．56(95％CI：1．14～2．14)，无抽油烟机的OR为3．77(95％CI：1．48～9．56)，食用动物油的OR为1．67(95％CI：1.25～2．24)，常吃胡萝卜的OR为0．47(95％CI：0．22～0．98)，饮酒的OR为6．58(95％CI：1.53～28．30)，家族肺癌史的OR为3．75(95％CI：1．64～8．58)。结论 CYP1A1和GSTM1基因多态与肺癌发病无明显的关联，吸烟、饮酒、食用动物油、家族肺癌吏以及无抽油烟机是肺癌的危险因素，而高化程度和常吃胡萝卜与降低肺癌风险有关。     

肺癌易感性标记物与肺癌关系的病例对照研究

目的探讨谷胱甘肽转移酶(GST)和细胞色素CYP1A1、CYP2E1多态性与肺癌易感性的关系。方法用病例对照研究方法，收集广东籍新发原发性肺癌病人91例及同期非肺部疾患住院病人91例作对照。采用聚合酶链式反应(PCR)和限制性片段长度多态性(RFLP)技术检测病例和对照的CYP1A1、CYP2E1和GSTM1基因多态性。结果CYP1A1突变型(m2m2)与野生型(m1m1)比较，OR值1．51；CYP2E1C1C1型与C1C2型比较，OR值1．80；C2C2型与C1C2型比较，OR值5．48；GSTM1基因缺失型与正常型比较；OR值1．26。两种基因联合分析结果表明：GSTM，基因缺失并携带CYP1A1m2m2与GSTM1基因正常并携带CYP1A1m1m1者比较，OR值2．29，GSTM1基因缺失并携带CYP2E1C1C1型者与GSTM1基因正常并携带CYP2E1C1C2型者比较，OR值2．13，携带CYP1A1m2m2型以及CYP2E1C1C1型者与携带CYP1A1m1m1型和CYPE1C1C2型者比较，OR值3．00。3种基因联合作用分析结果表明：携带CYP1A1m2m2型以及CYP2E1C1C1型并且GSTM1基因缺失者比携带CYP1A1m1m1型和CYP2E1ClC2型且GSTM1基因正常者提高了患肺癌的危险性，OR值3．97。结论CYP1A1、CYP2E1和GSTM1在单因素分析中末显示出与肺癌风险的联系，2个基因和3种基因的联合作用似乎可以提高患肺癌的危险性，但无统计学意义。提示这3种基因均不是肺癌个体易感性的主效基因，可能是次效基因。     

广东省梅州地区客家人群GSTP1和GSTM1基因多态性研究

目的了解谷胱甘肽硫转移酶P1(GSTP1)、M1(GSTM1)基因多态性在广东梅州地区人群中的分布规律.方法采用聚合酶链式反应-限制性酶切片段长度多态性(PCR-RFLP)方法和以β-Globin为内对照的双重PCR法分别检测广东省梅州地区512名健康客家居民GSTP1和GSTM1基因型.结果调查人群GSTP1基因3种基因型GSTP1 A/A、GSTP1A/G、GSTP1 G/G分布频率分别为69.1%,28.2%,2.7%;GSTM1基因缺失型分布频率为62.1%;GSTM1基因在饮酒人群与不饮酒人群中的分布差异有统计学意义(P＜0.05),GSTP1基因在吸烟与不吸烟人群中的分布差异有统计学意义(P＜0.01),吸烟人群中GSTP1 A/A基因型分布频率较低(62.5%),GSTP1 A/G基因型分布频率较低(29.2%),GSTP1 G/G基因型分布频率较高(8.3%).GSTM1基因型分布与高血压家族史有相关性(OR=1.868,95%CI 1.119～3.119).结论 GSTP1基因多态性在广东梅州地区吸烟与不吸烟客家人群中分布有差异,GSTM1在广东梅州地区饮酒与不饮酒客家人群中分布有差异,GSTM1基因型分布与高血压家族史有相关性.     

GSTM1基因多态及膳食因素与肺癌关系的研究

目的 研究谷胱苷肽硫转移酶M1(GSTMl)基因多态性及膳食因素与广州地区肺癌发生的关系。方法 采用成组病例-对照研究方法，病例58例，对照62例，制定统一的调查表进行调查，用PCR检测GSTM1基因多态性。结果 GSTM1基因多态性与肺癌危险性关系无显著性差异(OR1．73，95％CI0．84～3．58)；Logistic单因素分析显示：胡萝卜摄入频率与肺癌发生的危险性呈负相关(OR0．24，95％CI0．10～0．58)，而用动物油脂炒菜与肺癌的发生呈正相关(OR5．34，95％CI1．13～20．16)。非条件logistic多因素回归分析校正吸烟等非膳食烹调因素后，胡萝卜摄入频率(OR0．18，95％C10．05～0．65)仍与肺癌发生负相关；不常吃胡萝卜联合GSTM1缺失发生肺癌的危险性显著增加(OR6．30，95％CI1．88～21．05)。结论 GSTM1基因单独作用时与肺癌关系不明显；用动物油脂炒菜显著增加肺癌发生的危险性。常摄入胡萝卜可显著降低肺癌发生危险性。GSTM1基因多态性与胡萝卜摄入间存在协同作用。     

血清硒与GSTM1基因多态性在肺癌发生中的交互作用

目的:探讨血清硒水平与GSTM1基因多态性在肺癌发生中的交互作用。方法:采用成组病例-对照研究方法,选择广州地区原发性肺癌患者58例,对照62例,用PCR检测GSTM1基因多态性,用氢化物发生原子荧光光谱法(GHAFS)测定血清硒。结果:病例组血清硒水平显著低于对照组(P=0.001),OR为4.44(95%CI1.64～12.01);GSTM1基因多态性与肺癌危险性关系无统计学意义(OR1.73,95%CI0.84～3.58);血清硒水平低与GSTM1缺失在肺癌发生中有正交互作用。归因交互效应为3.40,归因交互效应百分比为60.18%。结论:血清硒水平与肺癌发生负相关;GSTM1基因单独作用时与肺癌关系不明显,但血清硒水平低与GSTM1缺失之间存在协同作用,使肺癌发生的危险性显著增加。     

Association of Xenobiotic Metabolizing Enzymes Genetic Polymorphisms With Esophageal Cancer in Kashmir Valley and Influence of Environmental Factors

The Kashmir Valley has an elevated incidence rate of esophageal cancer (EC). Several environmental and genetic factors have been suspected for development of EC. A case-control study was performed in 135 EC patients and 195 healthy controls to analyze association of polymorphisms in glutathione S-transferase (GST) mu (GSTM1), GST theta (GSTT1), GST pi (GSTP1), GSTM3, Cytochrome P450 (CYP)1A1, and CYP2E1 genes with susceptibility to EC as well as their interaction with environmental factors such as smoking and high consumption of salted tea in Kashmir valley. All subjects were genotyped through polymerase chain reaction restriction fragment length polymorphism. Data was statistically analyzed using the chi-square test and logistic regression model. Results showed that GSTP1313 val/val and CYP2E1c1c2 genotypes imparted risk for esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma [EADC; odds ratio (OR) = 3.24, 95% confidence interval (CI) = 1.30–8.05; OR = 4.20, 95% CI = 1.65–10.70], respectively. GSTM3AB genotype/B allele was found to be associated with low risk for EC. Tobacco smoking through hukka (water pipe) and consumption of salted tea itself were high risk factors for developing EC (OR = 21.44, 95% CI = 11.63–39.54; OR = 14.86, 95% CI = 8.41–26.24), and the risks were modulated through the interaction of GSTM3AB, GSTP1val/val genotypes. In conclusion, GSTP1val/val and CYP2E1c1c2 genotypes/c2 allele increased the risk of ESCC and EADC, respectively, in the Kashmiri population; whereas GSTM3AB genotype imparted lower risk for both ESCC and EADC.     

GSTM1和GSTT1基因多态性与女性肺癌易感性的关系

目的：探讨谷胱苷肽硫转移酶M1（glutathione S-transferaseM1,GSTM1)和T1（glutathione S-transferaseT1,GSTT1)基因多态性与女性肺癌遗传易感性的关系。方法：采用病例－对照研究方法和多重PCR技术检测女性肺癌病例组42人和健康对照组55人的GSTM1和GSTT1基因缺陷型的频率，并评价GSTM1和GSTT1基因型以及他们之间的交互作用与肺癌遗传易感性的关系。结果：在本次研究的人群中，病例组GSTM1和GSTT1基因缺陷型的频率分别为66．7％和45．2％，对照组为54．5％和38．2％，GSTM1基因缺陷型和GSTT1基因缺陷型的频率在病例组和对照组之间均无显性差异（P＞0．05）。在不吸烟的女性人群中，GSTM1基因缺陷型携带患肺癌的危险性是GSTM1基因功能型携带的2．557倍（P＝0．046）；GSTT1基因缺陷型则有女性肺癌的发生无显关联（P＝0．557）。此外，GSTT1基因型与GSTM1基因型之间亦无明显的交互作用（P＞0．05）。结论：GSTM1基因缺陷型可能是非吸烟女性患肺癌的重要危险因素。GSTT1基因缺失则可能与肺癌的发生无关，在女性肺癌的发生过程中GSTM1和GSTT1可能不存在交互作用。     

肺癌组织中P63、TTF-1、CK7水平对肺癌的鉴别诊断分析

目的探讨肺癌组织中P63蛋白(P63)、甲状腺转录因子-1 (TTF-1)、细胞角蛋白7 (CK7)水平对肺癌的鉴别诊断价值。方法选择2017年1月至2020年1月我院的86例肺癌穿刺活检样本,以病理检测作为"金标准",采用免疫组织化学染色法(S-P检测法)检测样本中P63、 TTF-1、 CK7水平表达情况,根据表达情况分析鉴别诊断鳞癌、腺癌、小细胞癌及腺鳞癌的价值。结果 P63在鳞癌、腺癌、小细胞癌及腺鳞癌阳性表达率分别为100.00%、 5.88%、 0.00%、 100.00%;TTF-1在鳞癌、腺癌、小细胞癌及腺鳞癌阳性表达率分别为0.00%、 94.12%、 90.91%、 100.00%;CK7在鳞癌、腺癌、小细胞癌及腺鳞癌阳性表达率分别为8.57%、 94.12%、 27.27%、 100.00%。P63、 TTF-1、 CK7分别在鳞癌、腺癌、小细胞癌及腺鳞癌中阳性表达率比较,差异有统计学意义(P <0.05)。结论 P63在鳞癌中呈高表达,TTF-1在小细胞癌、腺癌中呈高表达,CK7在腺癌中呈高表达,P63、 TTF-1、 CK7水平对肺癌的鉴别诊断具有良好的应用价值。     

Alcohol Consumption and Risk of Lung Cancer in the VITamins And Lifestyle Study

The effect of alcoholic beverage consumption on lung cancer risk was investigated in the VITamins And Lifestyle (VITAL) Study. The VITAL study is a prospective cohort of residents aged 50–76 yr in Washington state. Five hundred and eighty incident lung cancer cases diagnosed between study baseline (2000–2002) and 2007 were identified among 66,186 participants without previous cancer through the Washington Surveillance Epidemiology and End Result cancer registry. Multivariable Cox's regression was used to examine the effects of beer, red wine, white wine, liquor, combined alcoholic beverage intake at study baseline, and alcohol intake at age 30 and 45 on lung cancer risk, with careful adjustment for smoking. There was no clear association between lung cancer and consumption of beer, red wine, white wine, or liquor at ≥1 drink/day. Combined alcoholic beverage intake of up to ≥3 drink/day was not associated with elevated overall lung cancer risk. Heavy consumption of alcohol at study baseline and at age 45 was, however, associated with more than doubling of risk for squamous cell carcinoma (hazard ratio for ≥3 drink/day at study baseline = 2.54, 95% CI: 1.36–4.73, P value for linear trend = 0.002) but not for adenocarcinoma. Alcohol intake at age 30 was not associated with lung cancer risk.     

CYP1A1基因多态性和GSTM1缺失与肺癌易感性的关系

[目的]探讨CYPlAl基因异亮氨酸(Ile)-缬氨酸(Val)位点多态性和GSTMl缺失与肺癌易感性的关系。[方法]以病例-对照方法,采用PCR技术检测82例原发性肺癌患者和91例对照者的CYPlAl基因Ile-Val位点多态性与GSTMl基因的缺失。[结果]Ile-Val3种多态基因型在肺癌组和对照组分布差异有显著性(P<0.05),Ile／Val、Val／Val基因型在肺癌组的分布频率明显高于对照组;logistic回归分析结果显示Ile／Val、Val／Val基因型患肺癌的危险性分别是Ile／Ile基因型的1.969(95％CI:1.012-3.828)倍和3.150倍(95％CI:1.278-7.761);GSTMl基因缺失在两组的分布频率差异有显著性(P<0.05,OR=2.157)。进一步联合CYPlAl多态性分析显示GSTMl缺失的个体同时携带Ile／Val或Val／Val基因型患肺癌的危险性较单独具有一种危险因子患肺癌的危险性显著增加(OR=5.538)。[结论]CYPlAl第7外显子的Ile／Val、Val／Val基因型和GSTMl缺失与肺癌的易感性有关,可望作为肺癌易感人群筛选的重要指标。     

Role of metabolic polymorphisms in lung carcinogenesis]

Metabolism of most chemical carcinogens in humans is thought to occur in two distinct phases. The carcinogens exert their effect only after being metabolically activated to intermediates (phase I), which are capable of binding to DNA and causing mutations. The most ubiquitous phase I catalysts are the cytochrome P450s (CYPs). There is convincing epidemiological evidence that lung cancer risk associated with polycyclic aromatic hydrocarbons (PAHs) is mediated in part by aryl hydrocarbon hydroxylase (AHH), which is used as an indicator of the phenotype of CYP1A1. Since AHH is responsible for the activation PAHs in cigarette smoke, it may be important in the causation of lung cancer. Kellermann et al. reported a significant positive correlation between AHH inducibility and susceptibility to lung cancer. The finding, however, has been both supported and refuted by subsequent investigators. Advances in molecular biology have allowed many allelic variants of several drug metabolizing enzymes so that individuals with the susceptible genotypes can be determined easily. A close association between development of lung cancer and homozygous rare genotypes in MspI and Ile-Val polymorphisms of CYP1A1 gene has been recently reported in some Japanese populations. The association between GSTM1 polymorphism and lung cancer risk is not so strong, however. Following the phase I reaction, phase II enzymes such as glutathione S-transferases (GSTs) are responsible for detoxification of activated forms PAH-epoxides. GSTs form a superfamily of genes consisting of four distinct families, named Alpha, Mu, Pi and Theta. The GSTM1, GSTT1 and GSTP1 genes are polymorphic in humans. The phenotypic absence of GSTM1 activity is due to a homozygous inherited deletion of the gene, the null genotype. The homozygous deletion of GSTM1 genes has been shown to occur in approximately 50% of the populations of various ethnic origins. The GSTM1 null genotype confrs a moderately increased risk of smoking-related lung cancer, however. Genetically determined susceptibility to lung cancer may depend on the metabolic balance between phase I and phase II enzymes. Risk of lung cancer, especially squamous cell carcinoma is shown to be remarkably increased in individuals with a combination of a homozygous rare allele of the CYP1A1 gene and the nulled GSTM1 gene, compared with those having other combinations of genotypes. Individuals with susceptible genotypes may become important for the prevention of lung cancer.