口腔颌面部恶性肿瘤GSTT1、GSTM1基因多态性改变初步研究

目的探讨谷胱甘态转硫酶M1（GSIM1）和T1（GSTT1）基因型与口腔颌面部恶性肿瘤发生的相关性。方法采用多重PCR技术，对87例口腔颌面部恶性肿瘤病例和与之匹配的对照组87例GSTM1、GsTT1基因型进行检测。结果口腔颌面部恶性肿瘤患者与对照组GSTM1基因缺失频率分别为62．1％和44．8％，差异有显著性（χ^2=5．197，P=0．023），GSTM1基因缺失与口腔颌面部恶性肿瘤易感性有关（OR=2．014，95％CI=1．100～3．688）。GSTM1基因缺失同时暴露于吸烟者患颌面部恶性肿瘤的危险性显著增加（OR=5．477，95％CI=2．257～14．619）。结论GSTM1基因缺失型可能是口腔颌面部恶性肿瘤的易感基因型，GSTM1基因缺失与吸烟在口腔颌面部恶性肿瘤的发生、发展中可能具有协同作用。     

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。     

散发性大肠腺癌与谷胱甘肽转硫酶M1、T1基因型的关系

 目的　探讨中国浙江汉族人群散发性大肠腺癌（SCRAC）易感性与谷胱甘肽转硫酶（GST）M1、T1基因型及烟酒嗜好的关系。方法　应用多重聚合酶链反应技术检测118例SCRAC患者和140例健康对照的GSTM1和GSTT1基因型，采用Logistic回归分析GSTM1-、GSTT1-基因型及烟酒嗜好与SCRAC的相关性。结果　GSTM1-和GSTT1-基因型能增加SCRAC的易感性（OR＝1.711，95 % CI：1.043～2.805；OR＝1.734，95 % CI：1.057～2.843），而烟酒嗜好对SCRAC的易感性无影响（OR＝0.584，95 % CI：0.356～0.958；OR＝0.378，95 % CI：0.217～0.657）；根据SCRAC临床特征进一步分层分析，发现GSTM1-和GSTT1-基因型均与年龄因素无关（P＞0.05）；GSTM1-基因型在远端SCRAC（P＝0.021）、Duke C期SCRAC（P＝0.003）及低分化SCRAC（P＝0.020）中的分布频率均明显增高；GSTT1-基因型则仅在Duke C期SCRAC中明显增高（P＝0.041），而与SCRAC的部位及组织分化程度无关（P＞0.05）。另发现GSTM1-／GSTT1-纯合子基因型在SCRAC患者中明显增高（P ＝0.023）。结论　GST基因型与中国浙江汉族人群SCRAC明显相关， GSTM1-和GSTT1-基因型能增加SCRAC的易感性，而烟酒嗜好对SCRAC的易感性无影响。     

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、GSTM1）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153例；人群对照223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（59．64％，P＝0．0024）；多因素调整OR＝2．33，95％CI＝1．39－3．92）。吸烟或不饮茶与GSM1－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。     

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     

GSTM1基因多态性和膀胱癌遗传易感性关系

目的：探讨谷胱甘肽转移酶（GSTMl）基因多态性与膀胱癌遗传易感性的关系。方法：采用面访填写调查表，以PCR技术、病例一对照研究方法，对252例病理证实原发膀胱移行细胞癌患者和320例健康对照者的GSTM1基因型进行检测。结果：膀胱癌患者GSTM1缺失基因型频率为45．2％。对照组为30．9％，两组比较差别有显著性意义（P〈0．05），OR值为1．89（95％CI=1．28～4．40）。吸烟者中，患者组GSTM1缺失基因型频率为66．2％，对照组为27．3％，差别显著（P〈0．01），OR值为8．9（95％CI=5．36～14．82）。同时憋屎及有家族肿瘤史也能增加患膀胱癌的危险性，但多饮牛奶则能降低膀胱癌的危险性，而水果摄入多少与膀胱癌发生危险性无统计学意义。结论：GSTM1基因多态性与膀胱癌易感性有关，该基因多态性与吸烟在膀胱癌的发生发展中起协同作用。     

洛阳市GSTM1和GSTT1缺失基因型与肝癌的遗传易感性

目的探讨肝癌低发区谷胱甘肽转硫酶(GST)M1和T1的缺失基因型与肝癌的关系.方法应用多重PCR技术检测洛阳市95例肝癌患者和103例对照的GSTM1和GSTT1基因型.结果病例组GSTM1缺失基因型的频率为0.705,对照组为0.502,两者差异有显著性(x2=8.28,P=0.004),OR值为2.35(95%CI:1.25～4.41);病例组GSTT1缺失基因型的频率为0.611,对照组为0.437,两者差异有显著性(x2=5.97,P=0.015),OR值为2.02(95%CI:1.10～3.71).叉生分析表明该两因素在肝癌发生中有协同作用(x2=14.83,P=0.002),同时具有两个缺失基因型时,OR值为5.57(95%CI:2.03～15.66);GSTM1和GSTT1缺失基因型均与吸烟有协同作用,OR值分别为5.84(95%CI:2.26～15.47)和5.51(95%CI:2.13～14.54);GSTM1缺失基因型与饮酒有协同作用,OR值为3.31(95%CI:1.47～7.49),而GSTT1缺失基因型与饮酒无协同作用.结论在肝癌低发区GSTM1和GSTT1缺失基因型是肝癌的易感基因型.     

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。     

中国人群GSTM1基因多态性与肺癌易感性的Meta分析

[目的]探讨中国人群中谷胱甘肽S-转移酶（GSTM1）基因多态性与肺癌易感性的关系。[方法]在Pubmed数据库、CNKI数据库、万方数据库、中国生物医学文献数据库（CBM）中查询文献,时间范围从各数据库建库至2014年5月。采用RevMan 5.1和SAS 9.1.3软件对国内外关于GSTM1基因多态性与肺癌易感性的研究进行合并效应值估计和异质性分析。[结果]37篇文献最终被纳入本次研究。Meta分析结果显示：GSTM1缺失基因型的中国人群患肺癌的风险明显增高（OR=1.45,95%CI：1.30～1.62）。亚组分析发现吸烟与非吸烟的中国人群中GSTM1缺失基因型患肺癌的风险分别为对照组的1.69倍（95%CI：1.39～2.07）和1.46倍（95%CI：1.17～1.82）。在病理类型的亚组分析中,GSTM1缺失基因型的中国人群患鳞状细胞肺癌的风险明显高于对照组（OR=1.35,95%CI：1.13～1.61）。[结论]GSTM1缺失基因型增加中国人群患肺癌的发病风险。     

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。     

GSTT1 genetic polymorphism and susceptibility to childhood acute lymphoblastic leukemia: a meta-analysis

Glutathione S-transferase T1 (GSTT1) genetic polymorphism has been considered as a risk factor for developing malignant diseases including acute lymphoblastic leukemia; however, the results from previous studies are inconsistent. We performed a meta-analysis of 16 published studies to investigate the association between GSTT1 null variant and risk of acute lymphoblastic leukemia in childhood. Between-study heterogeneity was assessed using the I ² statistic method. Odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CI) were pooled to assess the association. Those 16 studies were from 14 publications and included a total of 2,424 cases and 3,447 controls. Meta-analysis of a total of 16 studies showed that GSTT1 null variant was significantly associated with risk of childhood acute lymphoblastic leukemia (fixed-effect OR?=?1.22, 95 %CI 1.07–1.39, P?=?0.003, I ²?=?35 %). Subgroup analysis showed that GSTT1 null variant was significantly associated with risk of childhood acute lymphoblastic leukemia in Asians (fixed-effect OR?=?1.47, 95 %CI 1.16–1.85, P?=?0.001, I ²?=?0 %). However, there was no obvious association in both Caucasians (random-effect OR?=?1.07, 95 %CI 0.83–1.38, P?=?0.59, I ²?=?53 %) and Africans (random-effect OR?=?0.99, 95 %CI 0.31–3.10, P?=?0.98, I ²?=?72 %). Therefore, the GSTT1 null variant is significantly associated with susceptibility to childhood acute lymphoblastic leukemia in Asians.     

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 and GSTM1 polymorphisms and prostate cancer risk in Asians: a systematic review and meta-analysis

Glutathione S-transferases (GSTs) enzymes are involved in conjugation of electrophilic compounds to glutathione, and glutathione S-transferase T 1 (GSTT1) and glutathione S-transferase M 1 (GSTM1) polymorphisms have been implicated as risk factors for prostate cancer. We conducted a systematic review and meta-analysis to define the effect of GSTM1 and GSTT1 null genotypes on prostate cancer risk in Asians. We searched the PubMed and Wanfang Medical databases to identify published case–control studies investigating the associations of GSTM1 and GSTT1 null genotypes with risk of prostate cancer in Asians. Heterogeneity was assessed using Cochran’s Q statistic and odds ratios (OR) with corresponding 95 % confidence intervals (95 % CI) from individual studies were pooled using fixed or random effects models according to the heterogeneity. There were 18 studies (2,046 cases, 2,876 controls) on GSTM1 polymorphism, 15 studies (1,677 cases, 2,431 controls) on GSTT1 polymorphism, and 6 studies (675 cases, 853 controls) on GSTM1/GSTT1 interaction analysis. Overall, GSTM1 null genotype was significantly associated with increased risk of prostate cancer in Asians (random effects OR 1.80, 95 % CI 1.48–2.18, P?<?0.001), and GSTT1 null genotype was also significantly associated with increased risk of prostate cancer in Asians (random effects OR 1.40, 95 % CI 1.10–1.80, P?<?0.001). In addition, the GSTM1/GSTT dual null genotype was associated with higher risk of prostate cancer in Asians (random effects OR 2.14, 95 % CI 1.59–2.89, P?=?0.007). In conclusion, GSTM1 and GSTT1 null genotypes are associated with increased risk of prostate cancer in Asians, and GSTM1 and GSTT1 null genotypes are risk factors for the development of prostate cancer.     

Glutathione-S-Transferase Polymorphisms (GSTM1, GSTT1 and GSTP1) and Acute Leukemia Risk in Asians: a Meta-analysis

The association between glutathione-S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1) and riskof acute leukemia in Asians remains controversial. This study was therefore designed to evaluate the preciseassociation in 23 studies identified by a search of PubMed and several other databases, up to December 2013.Using random or fixed effects models odds ratios (ORs) with corresponding 95% confidence intervals (CIs) werecalculated. Heterogeneity across studies was assessed, and funnel plots were constructed to test for publicationbias. The meta-analysis showed positive associations between GST polymorphisms (GSTM1 and GSTT1 butnot GSTP1) and acute leukemia risk [(OR=1.47, 95% CI 1.18-1.83); (OR=1.32, 95% CI 1.07-1.62); (OR=1.01,95% CI 0.84-1.23), respectively] and heterogeneity between the studies. The results suggested that the GSTM1null genotype and GSTT1null genotype, but not the GSTP1 polymorphism, might be a potential risk factors foracute leukemia. Further well-designed studies are needed to confirm our findings.     

Association of GSTM1, GSTT1, GSTM3, and GSTP1 Genes Polymorphisms with Susceptibility to Osteosarcoma: a Case- Control Study and Meta-Analysis

Background: Some studies have investigated the association of GSTM1, GSTT1, GSTM3, and GSTP1polymorphisms with susceptibility to osteosarcoma; however, these studies results are inconsistent and inconclusive. Inorder to drive a more precise estimation, the present case-control study and meta-analysis was performed to investigateassociation of GSTM1, GSTT1, GSTM3, and GSTP1 polymorphisms with osteosarcoma. Methods: Eligible articleswere identified by a search of several electronic databases for the period up to May 5, 2018. Odds ratios were pooledusing either fixed-effects or random effects models. Results: Finally, a total of 24 case-control studies with 2,405osteosarcoma cases and 3,293 controls were included in the present meta-analysis. Overall, significantly increasedosteosarcoma risk was found when all studies were pooled into the meta-analysis of GSTT1 (Null vs. Present: OR= 1.24795% CI 1.020-1.524, P= 0.031) and GSTP1 polymorphism (B vs. A: OR= 8.899 95% CI 2.722-29.094, P≤0.001). Inthe stratified, significantly increased osteosarcoma risk was observed for GSTT1 polymorphism among Asians (Nullvs. Present: OR= 1.300 95% CI 1.034-1.635, P= 0.025), but not among Caucasians. Conclusions: This meta-analysisdemonstrated that GSTP1 and GSTT1 null genotype are associated with the risk of osteosarcoma. Future large welldesigned epidemiological studies are warranted to validate our results.     

Genetic Polymorphism of GSTM1 and GSTT1 and Risk of Prostatic Carcinoma - a Meta-analysis of 7,281 Prostate Cancer Cases and 9,082 Healthy Controls

Genetic polymorphisms constitute one of the reasons behind the racial variation in prostate cancer occurrence. Published studies regarding genetic associations of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) null deletion polymorphisms with prostatic carcinoma have generated inconsistent results among different populations. To date, even a single meta-analysis is not available representing the association of these genes with prostate cancer in different ethnic groups. Therefore, the aim of the current study was to provide a clear picture of GSTM1 and GSTT1 null deletion and risk of prostate cancer among different ethnic groups (i.e. Asians, Europeans, Americans, Africans and Eurasians). A systematic search was performed with the help of various search engines to find out the all the recent studies (2004 to 2015) evaluating the role of GSTM1 and GSTT1 deletion in prostate cancer development. Odds ratios (ORs) with 95% confidence interval (CI) of a total of 34 studies with 7,281 cases and 9,082 controls was analyzed using STATA and MedCalc software. Overall, GSTM1 deletion (OR 3.67; CI 1.39-9.85; P= 0.001) was strongly associated with prostatic cancer. In the sub group analysis GSTM1 null deletion was also significantly associated with prostate cancer among Asians (OR 4.84; CI 1.08-21.5; P= 0.03), Eurasians (OR 17.69; CI 9.87-31.70; <0.001) and Americans (OR 0.11; CI 0.01-1.06; P= 0.05). No association was observed among Europeans (P=0.42) and Africans (P= 0.40). As a whole GSTT1 null deletion (OR 0.85; CI 0.28-2.58; P= 0.77) did not show anyt significant association with prostate cancer risk among different populations. When the data were stratified into different groups, however, Africans demonstrated a significant association of GSTT1 null deletion (OR 1.95; CI 1.57-2.39; <0.001) with prostate cancer, whereas no association was found among Asians (P= 0.90), Americans (P= 0.50), Europeans (P= 0.89) and Eurasians (P= 1.0). In conclusion, both GSTM1 and GSTT1 may contribute to prostate cancer development but GSTM1 may prove to be a stronger candidate risk factor.     

Glutathione S-transferase M1 and T1 status and the risk of laryngeal cancer: a meta-analysis

Background: Polymorphic variations in GSTM1 and GSTT1 have been implicated as risk factors for various cancers. A number of studies conducted to assess their association with susceptibility to laryngeal carcinomas have yielded inconsistent and inconclusive results. In the present study, the possible association of laryngeal cancer risk with GSTM1 and GSTT1 null genotypes was explored by a meta analysis. Method: A meta-analysis was carried out on case-control studies collected from the literature. The pooled odds ratio (OR) and presence of publication bias in those studies were evaluated. Results: A total of 20 studies concerning laryngeal cancer were identified. The results showed that the pooled OR was 1.22 (95% CI 1.03-1.43) for the GSTM1 polymorphism while for GSTT1 polymorphism, the pooled OR was 1.23 (95% CI 0.96-1.58). No evidence of publication bias was detected among the included studies. Conclusion: The results suggest that the GSTM1 deficiency significantly increases susceptibility to laryngeal cancer whereas GSTT1 null genotype might not be a risk factor.     

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.     

The anti-tumor activities of interferon (IFN)-alpha in chronic myelogenous leukaemia (CML)-derived cell lines depends on the IFN-alpha subtypes

To evaluate the association between genetic polymorphism of GSTM1, GSTT1 and development of bladder cancer, a hospital-based case-control study was conducted in South Korea. The study population consisted of 232 histologically confirmed male bladder cancer cases and 165 male controls enrolled from urology departments with no previous history of cancer or systemic diseases in Seoul during 1997-1999. The GSTM1 null genotype was significantly associated with bladder cancer (OR: 1.6, 95% CI: 1.0-2.4), whereas the association observed for GSTT1 null genotype did not reach statistical significance (OR: 1.3, 95% CI: 0.9-2.0). There was a statistically significant multiple interaction between GSTM1 and GSTT1 genotype for risk of bladder cancer (P=0.04); the risk associated with the concurrent lack of both of the genes (OR: 2.2, 95% CI: 1.2-4.3) was greater than the product of risk in men with GSTM1 null/GSTT1 present (OR: 1.3, 95% CI: 0.7-2.5) or GSTM1 present/GSTT1 null (OR: 1.1, 95% CI: 0.6-2.2) genotype combinations.     

Glutathione s-transferase polymorphisms (GSTM1, GSTP1 and GSTT1) and the risk of acute leukaemia: a systematic review and meta-analysis

Glutathione s-transferase (GST) polymorphisms (GSTM1, GSTP1 and GSTT1) have been considered as risk factors for developing acute leukaemia in a number of studies; however the overall results of such studies are inconsistent. To investigate a putative association of GST polymorphisms with the risk of acute leukaemia, we performed a systematic review and meta-analysis of 30 published case-control studies. To take into account the possibility of heterogeneity across the studies, a statistical test was performed. The pooled odds ratios (ORs) were assessed using both a fixed-effects and a random-effects model. The pooled OR of acute leukaemia risks associated with GSTM1 null genotype, GSTP1 Val105 allele and GSTT1 null genotype were 1.22 (95% confidence interval (CI) 1.07-1.38), 1.07 (95% CI 1.00-1.13) and 1.19 (95% CI 1.00-1.41), respectively. Significantly increased risk of acute lymphoblastic leukaemia associated with GSTM1 and GSTT1 null genotypes was observed. Their pooled ORs were 1.24 (95% CI 1.17-1.31) and 1.30 (95% CI 1.06-1.60), respectively. We also found substantial evidence of heterogeneity between the studies. Our results suggest that GSTM1 and GSTT1, but not GSTP1 polymorphisms, appear to be associated with a modest increase in the risk of acute lymphoblastic leukaemia. It is conceivable that GSTM1 and GSTT1 null genotypes may thus play a role in leukemogenesis. A review of the 30 case-control studies indicates that greater attention should be paid to the design of future studies.