GSTM1、GSTT1基因多态性和吸烟与膀胱癌关系的病例对照研究

目的:应用全人群为基础的病例对照研究探讨GSTM1、GSTT1基因多态性和吸烟与膀胱癌危险性的关系。方法:采用多重PCR方法对404例正常对照和414例膀胱癌病例的基因组DNA进行GSTM1和GSTT1基因分型,应用非条件logistic回归分析方法进行统计分析。结果:与携带GSTM1( )基因型者比,GSTM1(-)基因型的男、女性患膀胱癌危险性分别为1.66(95%CI:1.18～2.33)和1.08(95%CI:0.59～1.98)。同样携带GSTM1(-)基因型,吸烟者比不吸烟者患膀胱癌的危险性更加明显。与不吸烟且携带GSTM1( )基因型男性比,GSTM1(-)基因型的目前吸烟者的OR值为2.99(95%CI:1.56～5.74),而携带GSTM1(-)基因型同时吸烟年限≥40年者OR为4.33(95%CI:2.14～8.73)。尽管女性吸烟例数较少,但携带GSTM1(-)基因型的吸烟女性患膀胱癌危险性显著高于不吸烟的GSTM1( )基因型者,OR值为6.72(95%CI:1.69～26.80)。与不吸烟且携带GSTT1( )基因型男性相比,携带GSTT1(-)基因型的吸烟者患男性膀胱癌危险的OR值为1.38(95%CI:0.79～2.42)。携带GSTT1(-)基因型的吸烟女性患膀胱癌危险性是不吸烟的GSTT1( )基因型者的3.04倍(95%CI:0.77～12.01)。结论:GSTM1(-)基因型能显著增加男性患膀胱癌的风险,该基因型与吸烟可能有一定的联合作用。GSTT1基因型可能与上海市区男、女性膀胱癌无关。     

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。     

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。     

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。     

GSTT1和GSTM1基因缺失多态与胃癌易感性

目的　探讨与致癌物解毒有关的谷胱甘肽转硫酶 (GST) T1和 M1基因遗传缺失多态与胃癌易感性的关系。方法　采用病例对照分子流行病学研究方法 ,以 PCR技术对福建省福州市 92例胃癌病例和 92例正常对照者的 GSTT1和 GSTM1基因型进行检测。结果　 GSTT1基因在胃癌病例和对照组中的缺失率分别为 5 3.3%和41.3% ,差异无显著性 (x2 =2 .6 4,P=0 .10 4)。而 GSTM1基因在胃癌病例和对照组中的缺失率分别为 6 9.6 %和5 2 .2 % ,差异具有显著性 (x2 =5 .84,P=0 .0 15 7)。携带 GSTM1(- )基因型者发生胃癌的危险性是携带 GSTM1( )基因型者的 2 .1倍 (OR=2 .10 ,95 % CI=1.10～ 4.0 1)。联合分析表明 ,GSTT1和 GSTM1基因之间可能存在联合作用 ,携带 GSTT1(- )和 GSTM1(- )基因型者发生胃癌的危险性高于携带 GSTT1( )和 GSTM1( )基因型者 (OR=4.6 7,95 % CI=1.5 5～ 14.41)。结论　 GSTM1基因缺失可能是胃癌发病的危险性因素之一     

GSTT1基因多态性与中国四川汉族人群肺癌遗传易感性关系的研究

背景与目的GSTs可能参与机体致癌物的解毒反应，如保护个体免受吸烟的损害，因此GSTs基因多态性被认为是个体是否患癌的易感因素。本研究的目的是探讨GSTT1基因多念性与中国四川汉族人群肺癌遗传易感性的关系。方法采用病例对照和PCR—RFLP方法检测中国四川汉族人群肺癌患者150例和健康对照者152例的GSTT1基因缺失型的频率，并评价其与吸烟和肺癌遗传易感性的关系。结果①GSTT1（-）基因型在肺癌组和对照组分别为54．7％(82／150)和38．2％(58/152)．二者间比较有显著性差异(OR=1．681，95％CI=1，009～2．803，P=0．046)；②GSTT1(-)基因型患肺鳞癌(OR=2．969．95％CI=1．511～5．834。P=0．002)及肺腺癌(OR=2．095．95％CI=1．060～4．140，P=0．033)的风险性明显增加；③吸烟者中GSTT1(-)基因型者患肺癌的风险是GSTT1( )者的4．051倍；①GSTT1(-)基因型者中，吸烟者患肺癌的风险是不吸烟者的53．885倍；⑤吸烟≥20包年者中，GSTT1(-)基因型者患肺癌的风险是GSTT1( )者的4．296倍。结论①(GSTT1(-)基因型增加四川汉族人群患肺癌的风险性．特别是增加患肺鳞癌的风险；②GSTT1(-)基因型和吸烟之间存在交互作用，吸烟量越大且为GSTT1(-)基因型者则患肺癌的风险性越大。     

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     

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。     

生长激素1基因多态性和烟酒习惯与结直肠癌易感性的关系

目的:研究生长激素1(growth hormone1,GH1)基因T1663A多态性与结直肠癌易感性的关系。方法:在江苏省进行了一个病例-对照研究(结直肠癌患者315例,人群对照439名),调查研究对象的生活习惯,抽取静脉血,提取白细胞DNA,采用PCR-RFLP检测研究对象的GH1T1663A基因型。结果:1)GH1T/T、T/A和A/A基因型分布频度在结直肠癌组分别为42.2%、46.7%和11.1%,对照组分别为38·1%、45·9%和16·0%,两组差异无统计学意义,χ2MH=3·907,P=0·142。但在调整性别、年龄、吸烟和饮酒习惯后,A/A基因型者与T/T基因型者相比,发生结直肠癌的危险性显著降低(OR=0·88,95%CI:0·78~0·99,P=0·0287)。2)多因素分析结果显示,饮酒者患结直肠癌的危险性显著增高(OR=1·96,95%CI:1·34~2·86,P=0·0005),A/A基因型与降低结直肠癌的危险性有关,而吸烟与增加或降低结直肠癌的危险性无显著相关。3)GH1基因多态与吸烟、饮酒相互作用的分层分析发现,在不吸烟者中,GH1A/A基因型者与T等位基因型者相比,发生结直肠癌的危险性显著降低(性别和年龄调整OR=0·50,95%CI:0·27~0·93);在不饮酒者中,GH1A/A基因型者发生结直肠癌的调整OR为0·56(95%CI:0·32~0·99)。结论:T1663A GH1基因的A/A基因型可降低结直肠癌易感性,特别是在不吸烟和不饮酒者中。     

代谢酶基因多态性与肺癌易感性关系的研究

目的　探讨代谢活化酶细胞色素P45 0 1A1(CYP1A1)、2D6(CYP2D6)、2E1(CYP2E1)和代谢解毒酶谷胱甘肽硫转移酶 (GSTM 1)基因多态性与肺癌易感性的关系及重度吸烟对肺癌易感性的影响。方法　采用PCR、PCR RFLP等技术检测 180例原发性肺癌患者及 2 2 4例肺部良性疾病患者和正常人 (对照组 )外周血代谢酶基因型。结果　CYP1A1突变等位基因 (m )、CYP2D6野生型等位基因 (w )、CYP2E1A基因型和GSTM 1功能缺失型 ( -)可使患肺癌的危险性增加到 1.5 0～ 1.5 8倍 (P <0 .0 5 )。携带GSTM 1( -)者若同时携带CYP1A1、2D6或 2E1中任意 1个易感基因型 ,可使患肺癌的危险性升高到 2 .2 4～ 2 .69倍 (P <0 .0 5 )。携带相同基因型者 ,重度吸烟比不吸烟者患肺癌的危险性显著升高。重度吸烟人群中携带 4种易感基因型者患肺癌的危险性显著增高 ,达 9.85倍 ( 95 %CI =2 .3 0～ 45 .71)。结论　代谢酶基因的易感等位基因携带者患肺癌的危险性上升 ,且与烟草致癌物暴露剂量呈正相关。     

Polymorphisms in GSTM1, GSTTI and GSTP1 and nasopharyngeal cancer in the east of China: a case-control study

Aim: The study was performed to assess the potential role of GSTM1, GSTT1 and GSTP1 polymorphisms in the risk of nasopharyngeal cancer in Chinese population. Method: We collected 182 cases undergoing pathologic examination and 366 controls from the affiliated hospital of Medical College of Qingdao University from April 2006 to July 2010. Genotyping was based upon duplex polymerase-chain-reactions with the PCR-CTPP method. Results: More smokers were found in NPC patients than controls, and a higher IgA/VCA+ . Individuals carrying null GSTM1 and GSTT1 had 1.76 and 2.01 fold risk of NPC when compared with non-null genotypes, respectively. A non-significant increase risk of NPC was found in individuals with 1b/1b genotype when compared with 1a/1a genotype (OR=1.32, 95%CI=0.60-2.94). When compared with non-null GSTM1 and GSTT1 genotypes, the combination of null/null GSTM1 and GSTT1 genotypes showed moderate increased risk of NPC (OR=3.03, 95% CI=1.74-5.08). Conclusion: Our study provides evidence that genetic deletion of GSTM1 and GSTT1 may contribute to increased susceptibility to NPC in Chinese population, while GSTP1 may not. Our findings provide information relevant to the prevention of NPC.     

Glutathione S-transferase gene polymorphisms and risk of gastric cancer in a Chinese population

Aim: The potential role of GSTM1, GSTT1 and GSTP1 polymorphisms in risk of gastric cancer in Chinese was studied. Methods: We collected 194 gastric cancers by pathologic examination and 412 controls from southern China during January 2007 to January 2011. Genotyping was based upon duplex polymerase-chain-reaction withthe PCR-CTPP method. Results: Individuals carrying null GSTM1 and GSTT1 had 1.49 and 1.96 fold risk sof gastric cancer when compared with respective non-null genotypes. We also found a non-significant 37% excess risk of gastric cancer among carriers of GSTP1 1b/1b genotype when compared with 1a/1a genotype (OR=1.37, 95% CI=0.81-2.25). The combination of null/null GSTM1 and GSTT1 genotypes showed higher increased risk of gastric cancer (OR=3.17, 95% CI=1.68-4.21). Moreover, cancers in ever smokers and ever drinkers were observed to be strongly associated with null GSTM1 and GSTT1, and a significant cancer risk was observed in positive H.pylori infection individuals with null GSTT1. Conclusion: Our study provided evidence that genetic deletion of GSTM1 and GSTT1 may contribute to increased susceptibility to gastric cancer in our Chinese population, while the GSTP1a/b polymorphism may not.     

GSTM1, GSTT1, and GSTP1 polymorphism and lung cancer risk in relation to tobacco smoking

The impact of genetic polymorphisms in GSTM1, GSTP1 or GSTT1 on susceptibility to lung cancer has received particular interest since these enzymes play a central role in detoxification of major classes of tobacco carcinogens. In the current German study we investigated the role of GSTM1, GSTT1 and GSTP1 polymorphisms as a genetic modifier of risk for individuals with lung cancer as susceptible genotypes especially in relation to tobacco smoking. The GSTM1, the GSTP1 as well as GSTT1-polymorphism were determined by real time PCR analysis in 446 lung cancer patients and 622 controls. The observed allele frequencies of the GSTP1 polymorphism in the population were within the range described for Caucasians. Multivariate analyses of lung cancer patients, who carried at least one mutant variant allele of GSTP1 (OR=1.03; 95%-CI: 0.76-1.39) did not show any elevated risks. GSTM1 or GSTT1 null-genotypes were found in 47.3% resp. 18.5% of the controls and in 52.5% resp. 16.8% of the cancer patients. The estimated risk of the GSTM1 null genotype for lung cancer was OR=1.34 (95%-CI: 0.99-1.81) and for the GSTT1 null genotype OR=0.88 (95%-CI: 0.59-1.32). When analyzed by histology no individual subtype of lung cancer was strongly associated with the polymorphisms. Lung cancer risk rose significantly with higher cumulative cigarette consumption confirming the association with smoking-related lung cancer risk. Stratified analysis between tobacco smoking and variant genotypes revealed for heavy smokers (>60 pack-years) increasing risks at the presence for at least one copy of the GSTP1 variant allele OR=50.56 (95%-CI: 15.52-164.79). The corresponding risks for GSTM1 null genotypes were OR=112.08 (95%-CI: 23.02-545.71) and for the GSTT1 null-genotype OR=158.49 (95%-CI: 17.75-1415.06) in smokers >60 pack-years. Analysing the interaction between tobacco smoking and the genotypes, combined smoking and having the susceptible genotypes did not show a joint effect. In this study polymorphisms of the GSTM1, GSTT1 or GSTP1 had no relevant modifying effect on lung cancer risk and cumulative smoking dose.     

Impact of GSTT1, GSTM1, GSTP1 and NAT2 genotypes on KRAS2 and TP53 gene mutations in colorectal cancer

Which carcinogens are of influence in the development of human colorectal cancers remains a question; one answer could be the finding that specific polymorphisms in xenobiotic metabolizing enzymes are related to particular mutations in cancer genes. KRAS2 and TP53 gene mutations as well as genotypes for GSTM1, GSTP1, GSTT1 and NAT2 were determined in an exploratory series of 165 stable colorectal cancers. Mutations in KRAS2 and TP53 were found in 34% and 57.5% of cases, respectively. The KRAS2 mutation frequency was significantly lower in patients with a GSTT1 null genotype than in those with a GSTT1 non-null genotype (18% vs. 38%, p = 0.03). The overall risk of KRAS2 mutation for patients with distal colorectal cancer and GSTT1 null genotype was 0.3 (95% CI 0.1-0.9) compared to patients with distal colorectal cancer and non-null GSTT1 genotype. The overall risk of KRAS2 mutation was similarly reduced (OR = 0.4, 95% CI 0.2-0.9) for patients with distal colorectal cancer and GSTP1 mutated genotypes compared to patients with distal colorectal cancer and wild-type genotype. Patients with GSTP1 wild-type genotype appeared to be at significantly lower risk for TP53 mutation compared to patients with mutated genotypes (p = 0.023). Our results suggest that GSTT1 and GSTP1 could play a role in the occurrence of KRAS2 and TP53 mutations in colorectal cancer and generate a hypothesis on the dietary factors that could be incriminated.     

Glutathione S-transferase M1 and T1 null genotypes and the risk of gastric and colorectal cancers.

Several polymorphic glutathione S-transferase (GST) enzymes are involved in the detoxification of active metabolites of many potential carcinogens and may therefore be important in modulating susceptibility to cancers. GSTM1 and GSTT1 are polymorphic, and the null alleles result in a lack of corresponding enzyme activities. Previous studies demonstrated that the GSTM1 and GSTT1 null genotypes correlated with an increased risk of developing some cancers. In this study, we determined GSTM1 and GSTT1 polymorphisms in a population of 131 healthy controls from the south of Iran, 46 patients with colorectal cancers, and 42 patients with gastric cancer. The gastric cancer risk statistically increased due to the GSTM1 null genotype (odds ratio (OR)=2.3, 95% confidence interval (CI): 1.15--4.95). On the other hand, the GSTT1 null genotype in gastric cancer and null genotypes of GSTM1 and GSTT1 in colorectal cancer were not statistically significant. Moreover, individuals showing the GSTM1 and GSTT1 null genotypes might exhibit a greater predisposition to gastric (OR=3.31, 95% CI: 1.14--9.57) and colorectal (OR=2.73, 95% CI: 0.94--7.95, P=0.07) cancers.     

Glulathione-S-transferases Gene Polymorphism in Prediction of Gastric Cancer Risk by Smoking and Helicobacter Pylori Infection Status

Aim: To evaluate the association of glutathione S-transferases gene polymorphisms with the risk of gastriccancer, with reference to smoking and Helicobacter pylori infection. Methods: We conducted a 1:1 matched casecontrolstudy with 410 gastric cancer cases and 410 cancer-free controls. Polymorphisms of GSTM1, GSTT1 andGSTP1 were determined using PCR-CTPP. Results: The GSTM1 and GSTT1 null genotypes were significantlyassociated with the risk of gastric cancer after adjusting for potential confounding factors (OR=1.68, 95%CI=1.32-2.23 for null GSTM1, OR=1.73; 95% CI=1.24-2.13 for null GSTT1). The combination of null GSTM1and null GSTT1 conferred an elevated risk (OR=2.54, 95% CI=1.55-3.39). However, no association was foundfor GSTP1 polymorphism The smoking modified the association of GSTM1 and GSTT1 null genotypes withthe risk of gastric cancer. Conclusion: GSTM1 and GSTT1 null genotypes are associated with increased risk ofgastric cancer, and smoking modifies the association.     

GSTT1, GSTM1 and GSTP1 genetic polymorphisms and interaction with tobacco, alcohol and occupational exposure in esophageal cancer patients from North India

Glutathione S-transferases(GSTs) are detoxification enzymes that provide critical defense against carcinogens. Our hypothesis was that altered frequencies of GST genotypes and environmental exposures might be associated with increased susceptibility for the development of esophageal cancer. A total of 100 esophageal cancer patients and 137 age and gender matched healthy controls were analyzed for GST polymorphisms. Frequencies of GSTT1 null, GSTM1 null and GSTP1 genotypes did not differ between patients and controls. However, a two-fold risk was observed for GSTM1 null genotype in adenocarcinoma (OR(odds ratio) 2.1; 95% CI(confidence intervals)=0.53-8.6). Further, we used a case only design to study gene-environment interactions in esophageal cancer. In patients with smoking habits, GSTM1 null and GSTP1 ile/ile genotype were at higher risk for esophageal cancer (OR 1.5; 95% CI=0.50-4.4 and OR 1.3; 95% CI=0.40-3.5), respectively. A moderate risk for cancer was observed from alcohol usage along with GSTM1 null(OR 1.3; 95% CI=0.50-3.6) and GSTP1 val/val genotypes(OR 1.2; 95% CI=0.20-5.7). Interaction of GST genotypes with occupational exposure did not affect risk for esophageal cancer. These findings suggest that genetic polymorphisms of GSTT1, GSTM1, and GSTP1 are not associated with higher risk of esophageal cancer. However, interaction of smoking or alcohol with GSTM1 null or GSTP1 ile/ile moderately increases the risk for esophageal cancer in North Indian population.     

Genetic Polymorphisms of Xenobiotic Metabolizing Genes (GSTM1, GSTT1, GSTP1), Gene-Gene Interaction with Association to Lung Cancer Risk in North India; A Case Control Study

Aim: In this case control study involving, 220 human subjects; polymorphisms in xenobiotic metabolizing genes (GST-M1, -T1 and -P1) and their association to lung cancer risk is being analysed among smokers and non-smokers. GSTM1 or GSTT1 gene polymorphism and amino acid changes in GSTP1 have been correlated and may be associated to lung cancer risk. Other factor includes exposure to environmental pollutants and life style choices. We have explored gene-gene and gene-environment interaction in the aetiology of lung cancer risk among north Indian population. Patients and Methods: For the study we have collected 120 lung cancer patient blood samples from Kamala Nehru Memorial Cancer Hospital, Allahabad, Uttar Pradesh and 100 matched controls. DNA was isolated and GST-M1 and - T1 genotyping were assessed by multiplex PCR whereas the GSTP1 polymorphism was analysed using restriction fragment length polymorphism. The risk of lung carcinogenesis was assessed using logistic regression analysis calculating the odd ratio (OR) with 95% confidence interval (CI). Results: The risk of lung carcinogenesis was three fold higher for null GSTT1 (OR=3.045, 95%CI=1.750-5.301, p-value <0.001) genotype; whereas other two types; GSTM1 (OR= 1.342, 95% CI=0.788-2.284, p-value=0.270) and GSTP1 (OR=0.806, 95% CI=0.526-1.236, p-value=0.323) showed no association to lung cancer susceptibility respectively. Smokers diagnosed with lung cancer had more null genotypes for GSTT1 (OR=4.773, 95%CI=1.939-11.751, p<0.001). The ‘at risk’ genotype combination GSTM1 (null) /GSTT1 (null) (OR=1.76, 95%CI; 0.920-3.370, p-value=0.03) showed increased susceptibility to lung cancer risk. The genotype combination of GSTT1 (null)/GSTP1 (Ile/Ile) (p=0.009) was associated with increased lung cancer risk. Conclusion: The results of this study suggest that; GSTT1 null genotype were more susceptible for lung cancer risk and smoking increases the susceptibility for lung cancer several folds among the North Indian population. Gene-gene interaction for null genotypes of GSTM1 and GSTT1 were correlated with higher risk of having lung cancer.