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1.
Background: Glutathione S-transferase M1 (GSTM1) have been reported to be associated with hepatocellular carcinoma. However, the effect of the GSTM1 null genotype was divergent in the literature and we therefore performed the present meta-analysis to explore the relationship in detail. Materials and Methods: Reported studies were searched from 1990 to March 1, 2014 in PubMed and Wanfang Med Online. The total odds oatio (OR) and 95% CI were calculated and analyzed by Review Manager 5.1 and STATE 12. Results: Total OR was calculated from 26 articles with 3,769 cases and 5,517 controls and the association proved significant (OR [95%CI]=1.50 [1.25, 1.80], P<0.05) in the Chinese population. However, there was no significant association between hepatocellular carcinoma risk among subjects carrying the GSTM1 null genotype (OR [95%CI]=1.20 [0.88-1.64], P=0.24) in subgroups of publication in English and in Indian populations (OR [95%CI]=1.80 [0.80-4.20], P=0.15). Conclusions: The GSTM1 deletion polymorphism might not have a significant effect on the susceptibility of hepatocellular carcinoma overall.  相似文献   

2.
Objective: Genetic variation is considered to strongly impact on detoxification of carcinogens and thereforeis related to cancer risk. However, findings for the null genotypes of GSTT1 and GSTM1 have not always beenconsistent. Therefore the present meta-analysis was conducted. Methods: We accessed the reported study atdifferent research areas and used various databases, including PubMed and Wanfang Med Onlion from 1990to May 1st 2013. We calculated the odds ratio (OR), 95% confidence interval (CI) and P value for oral cancerby using Review Manager 5.1 and STATE 12. Results: We found that there was no increased oral cancer riskamong subjects carrying GSTM1 and GSTT1 null genotype (OR=1.35, 95%CI=0.68-2.68, P=0.39) and (OR=1.41,95%CI=0.72-2.77, P=0.31) in the Chinese population. In contrast, in studies in India a significant correlationbetween GSTM1 null genotype and oral cancer was observed (OR=1.59, 95%CI=1.20-2.11, P=0.001), but not inGSTT1 (OR=1.21, 95% CI = 0.84-1.74, P=0.31). Conclusion: We discovered that GSTM1 deletion polymorphismhad a significant effect on the susceptibility of oral cancer in the Indian population.  相似文献   

3.
Objective: The conclusions of published reports on the relationship between the glutathione S-transferaseM3 (GSTM3) A/B gene polymorphism and the risk of lung cancer are still debated. This meta-analysis wasperformed to evaluate the association between GSTM3 and the risk of lung cancer. Methods: Associationinvestigations were identified from PubMed, Embase, and Cochrane Library, and eligible studies were includedand synthesized using a meta-analysis method. Results: Eight reports were included into this meta-analysis forthe association of GSTM3 A/B gene polymorphism and lung cancer susceptibility, covering 1,854 patients withlung cancer and 1,926 controls. No association between the GSTM3 A/B gene polymorphism and lung cancerwas found in this meta-analysis (B allele: OR = 1.25, 95% CI: 0.89-1.76, P = 0.20; BB genotype: OR = 1.53, 95%CI: 0.71-3.32, P = 0.28; AA genotype: OR = 0.85, 95% CI: 0.59-1.23, P = 0.39). Conclusions: The GSTM3 A/Bgene polymorphism is not associated with lung cancer susceptibility. However, more studies on the relationshipbetween GSTM3 A/B gene polymorphism and the risk of lung cancer should be performed in the future.  相似文献   

4.
Objective(s): Lung cancer, caused primarily by smoking, is one of the leading determinants of mortality throughoutthe world. Here we investigated the effects of polymorphisms in two enzymes, i.e., GSTT1 and GSTM1, related tothe antioxidant defense line against carcinogens associated with lung cancer among a select group of Iranian people.Materials and Methods: One hundred and twenty lung cancer patients from two referral centers in Tehran, Iran, wererecruited for comparison with 120 healthy controls. Genomic DNA was extracted from the FFPE tumor tissues ofthe select cases and peripheral blood buffy coats of healthy controls. The polymorphisms of GSTT1 and GSTM1 wereinvestigated by multiplex polymerase chain reaction. Results: With the 240 samples studied, no specific relationshipwith lung cancer was discerned for the GSTM1 (P=0.35; OR=1/33; 95% CI=0.79-2.25) polymorphism, but the GSTT1(P=0.005; OR=2.4; CI=1.32-4.35) gene polymorphism revealed a notable association on logistic regression, takinginto account age and sex factors. Furthermore, the GSTT1 genotype distribution in patients with LSCC was differentfrom that of healthy cases (P=0.006; OR=3.11; CI=1.38-7.04). The risk of developing lung cancer with the T0M1genotype was 3.46 times higher than with T1M1 genotype (P=0.002; OR=3.46; CI=1.61-7.46). Moreover, the risk ofdeveloping LSCC cancer in people with T0M1 genotypes was significantly elevated (P=0.004; OR=4.5; CI=1.62-12.52).Conclusion: Unlike GSTM1, the GSTT1 genotype distribution is associated with the incidence of lung cancer in Iranianpeople. Different types of lung cancer appear to show various correlations with GST polymorphisms in this regard.  相似文献   

5.
Background/Aims: Glutathione S-transferase T1 (GSTT1), a phase-II enzyme, plays an important rolein detoxification of carcinogen electrophiles. Many studies have investigated the association between GSTT1polymorphism and esophageal cancer risk in Asian populations, but its actual impact is not clear owing toapparent inconsistencies among those studies. Thus, a meta-analysis was performed to explore the effect of GSTT1polymorphism on the risk of developing esophageal cancer. Methods: A literature search of PubMed, Embase, andWanfang databases up to August 2012 was conducted and 15 eligible papers were finally selected, involving a totalof 1,626 esophageal cancer cases and 2,216 controls. We used the pooled odds ratio (OR) with its corresponding95% confidence interval (95%CI) to estimate the association of GSTT1 polymorphism with esophageal cancerrisk. Subgroup analyses and sensitivity analyses were performed to further identify the association. Results:Meta-analysis of total studies showed the null genotype of GSTT1 was significantly associated with an increasedrisk of esophageal cancer in Asians (OR=1.26, 95%CI=1.05-1.52, POR=0.015, I2=42.7%). Subgroup analyses bysample size and countries also identified a significant association. Sensitivity analysis further demonstrated arelationship of GSTT1 polymorphism to esophageal cancer risk in Asians. Conclusions: The present meta-analysisof available data showed a significant association between the null genotype of GSTT1 and an increased risk ofesophageal cancer in Asians, particularly in China.  相似文献   

6.
目的 探讨谷胱甘肽硫转移酶A1(GSTA1)基因多态性与前列腺癌及膀胱癌易感性的关系.方法 通过检索PubMed等数据库,获取GSTA1基因多态性与前列腺癌或膀胱癌的文献9篇,对1989例病例和2246例对照进行meta分析,以比值比(OR)和95%可信区间(CI)作为效应指标.结果 各遗传模型的Meta分析显示:GSTA1基因多态性与前列腺癌易感性的相关性无统计学意义[(AA vs BB:OR=0.92,95%CI:0.68~1.23,P=0.56);(AB vs BB:OR=1.02,95%CI:0.86~1.21,P=0.83);(AA/AB vs BB OR=1.01,95%CI:0.86~1.17,P=0.93);(AA vs AB/BB:OR=0.91,95%CI:0.69~1.20,P=0.51)].各遗传模型的Meta分析显示:GSTA1基因多态性与膀胱癌易感性的相关性无统计学意义[(AA vs BB:OR=0.97,95%CI:0.71~1.33,P=0.85);(AB vs BB:OR=1.11,95%CI:0.93~1.31,P=0.25);(AA/AB vs BB OR=1.07,95%CI:0.92~1.25,P=0.37);(AA vs AB/BB:OR=0.87,95%CI:0.64~1.18,P=0.37)].结论 单独的GSTA1基因多态性不是前列腺癌和膀胱癌的易感因素.  相似文献   

7.
Polymorphisms in glutathione S-transferases (GSTs) may predispose to lung cancer through deficient detoxification ‍of carcinogenic or toxic constituents in cigarette smoke, although previous results have been conflicting. Three GST ‍polymorphisms (GSTM1, GSTT1 and GSTP1) were determined among 86 male patients with lung carcinomas and ‍88 healthy male subjects. We found no significant increase in the risk of lung cancer for any genotypes for the nulled ‍GSTM1 [odds ratio (OR)=2.0; 95% confidence interval (95% CI)= 0.8-5.3], the nulled GSTT1 (OR=2.0; 95% CI=0.8- ‍5.1) or the mutated (the presence of a Val-105 allele) GSTP1 (OR=0.96; 95% CI=0.4-5.5). The GST polymorphisms ‍alone may thus not be associated with susceptibility to lung carcinogenesis in male Japanese. However, individuals ‍with a concurrent lack of GSTM1 and GSTT1 had a significantly increased risk (OR=2.7; 95% CI=1.0-7.4) when ‍compared with those having at least one of these genes. No other combinations were associated with lung cancer ‍risk. These results suggest that there may be carcinogenic intermediates in cigarette smoke that are substrates for ‍both GSTM1 and GSTT1 enzymes and that lung cancer risk is increased for individuals who are doubly deleted at ‍GSTM1 and GSTT1 gene loci. Additional large studies are needed to confirm this observation.  相似文献   

8.
Lung cancer is closely associated with cigarette smoking. Aromatic hydrocarbons in smoke, including benzo[n]pyrene, first require metabolic activation by Phase I enzymes, cytochrome P450, to their ultimate forms, and these activated forms are then subjected to detoxification by Phase II enzymes, especially glutathione S-transferases. Thus, genetically determined susceptibility to lung cancer may depend on the metabolic balance between Phase I and Phase II enzymes. In this study, we identified individuals genetically at high risk of lung cancer in terms of polymorphisms of the P450IA1 gene and GST1 gene. The relative risk of individuals with a combination of the genotypes of both a homozygous rare allele of the P450IA1 gene and the nulled GST1 gene was remarkably high at 5.8 for lung cancer and 9.1 for squamous cell carcinoma compared with other combinations of genotypes.  相似文献   

9.
目的在中国西南的广西壮族自治区的鼻咽癌高发区内研究谷胱甘肽硫转移酶M1与T1遗传多态性与鼻咽癌易感的相关性。方法病例与对照研究这些酶的遗传多态性(GSTM1和GSTT1零基因型),鼻咽癌总数为127例,对照207例。结果GSTM1和GSTT1零基因型的频数在NPC患者中较高,差异达统计学意义(P<0.001)。结论鼻咽癌是广西最常见癌症,GST酶与多种环境致癌物的解毒相关,同合子缺失GSTM1和GSTT1与数种癌相关,生鼻咽癌危险性已知与环境因素如吸烟和EB病毒感染相关联,我们的结果提示GSTM1和GSTT1缺失多态性与增加鼻咽癌易感性相关,若两种解毒酶基因同时缺失对鼻咽癌易感受性意义更重要。  相似文献   

10.
黄志刚 《中国肿瘤》2003,12(11):642-646
[目的]综合评价谷胱甘肽硫转移酶M1(GSTM1)基因多态性与食管癌易患性的相关性。[方法]应用Meta分析方法对国内外9篇有关GSTM1因多态性与食管癌的病例对照研究进行定量综合分析,共积累病例845例,对照1267例。统计处理采用Meta分析的固定效应模型和随机效应模型。[结果]在排除一个超溢值后,8个病例对照研究的合并OR为1.622,95%可信度为1.323~1.988。[结论]GSTM1基因多态性与食管癌的易患性有关,即GSTM1空白基因型可增加患食管癌的危险性。  相似文献   

11.
目的在中国西南的广西壮族自治区的鼻咽癌高发区内研究谷胱甘肽硫转移酶 M1与 T1遗传多态性与鼻咽癌易感的相关性。方法病例与对照研究这些酶的遗传多态性(GSTM1和 GSTT1零基因型),鼻咽癌总数为127例,对照207例。结果 GSTM1和 GSqT1零基因型的频数在 NPC 患者中较高,差异达统计学意义(P<0.001)。结论鼻咽癌是广西最常见癌症,GST 酶与多种环境致癌物的解毒相关,同合子缺失 GSTM1和 GSTT1与数种癌相关,生鼻咽癌危险性已知与环境因素如吸烟和 EB病毒感染相关联,我们的结果提示 GSTM1和 GSTF1缺失多态性与增加鼻咽癌易感性相关,若两种解毒酶基因同时缺失对鼻咽癌易感受性意义更重要。  相似文献   

12.
Background/Aims: Studies of associations between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and risk of colorectal cancer (CRC) in Asian populations have reported controversial results. Thus, a meta-analysis was performed to clarify the effects of GSTT1 polymorphism on the risk of developing colorectal cancer. Methods: A literature search of PubMed and EMBASE up to June 7, 2011 was conducted and 13 eligible papers were finally selected, involving totals of 4,832 CRC cases and 7,045 controls. Subgroup analyses were performed according to the sample size and the research designwith the software programs Review Manager (version 5.0.10) and STATA (version 9.2). Results: Analyses of all relevant studies showed an increased CRC risk was significantly associated with the null genotypes of GSTT1 (OR=1.09, 95%CI=1.01-1.17, POR=0.027; I2=40.2%). Besides, a more obvious association was observed after heterogeneity was eliminated (OR=1.13, 95%CI 1.04-1.23, POR=0.002; I2=0.0%). Subgroup analyses and sensitivity analysis further identified an association in Asians. Conclusions: This meta-analysis demonstrated the GSTT1 null genotype to be associated with an increased risk of CRC in Asian populations.  相似文献   

13.
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。  相似文献   

14.
Glutathione S-transferases (GSTs) play important roles in carcinogenic biotransformation processes, whichvary among individuals. Polymorphisms of the encoding genes are associated with alteration of detoxificationcapacity, resulting in a variable risk of cancer development. The present study was performed to determine theeffects of polymorphisms in GST (M1, P1, and T1) genes on susceptibility to liver cancer in Thais. We recruited140 hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients and 280 healthy volunteers forour unmatched case-control based association study. GSTM1 deletion and heterozygous deletion were determinedand discriminated by semi-quantitative denaturing high performance liquid chromatography (DHPLC). Apolymerase chain reaction - restriction fragment length polymorphisms (PCR-RFLPs) approach was utilized todetect the GSTP1 Ile105Val variant, while the GSTT1 null allele was detected by multiplex PCR. With resultsfor single locus associations, only GSTP1 Ile/Val showed a significant decrease in the risk of liver cancer (OR=0.58;95% CI: 0.36-0.90; p-value=0.016). GSTP1 (Ile/Val) interacted with the GSTT1 wild type to further decreasesusceptibility to liver cancer (OR=0.41; 95% CI: 0.18-0.93; p-value=0.029). Moreover, three locus interactionsof GSTP1 (Ile/Val or Val/Val) with either wild type or null alleles of both GSTM1 and GSTT1 decreased risk ofliver cancer. In conclusion the GSTP1 null genotype apparently causes decreased risk of liver cancer in Thais.The findings point to GSTP1 Ile105Val as a possible protective allele against liver cancer risk.  相似文献   

15.
CYP1A1、GSTM1基因多态性与肺癌易感性的研究   总被引:6,自引:1,他引:6  
目的:探讨CYP1A1、GSTM1基因多态性与肺癌易感性之间的相关性。方法:利用RFLP-PCR(限制性片段长度多态性-聚合酶链反应)方法检测65例原发性肺癌和60例非肿瘤患者CYP1A1、GSTM1基因,再用NcoI及HinfI两种内切酶识别CYP1A1等位基因亚型。结果:1)肺癌组与对照组CYP1A1等位基因型Ile/Ile、Ile/Val、Val/Val的频率总体分布无显著性差异;但肺癌组CYP1A1(Val/Val)基因型频率(18.5%)明显高于对照组(8.3%),两组差异有显著性(P<0.05)。2)肺癌组GSTM1(-)基因型的频率(63.1%)明显高于对照组(45.0%),P<0.05。3)两种等位基因联合分析发现,与携带CYP1A1(Ile/Ile)/GSTM1(+)基因型的个体相比:CYP1A1(Ile/Ile)/GSTM1(-)以及CYP1A1(Ile/Val+Val/Val)/GSTM1(+)基因型个体患肺癌的风险度较高,OR分别为3.82(95.0%CI,1.27~11.45)和3.5(95.0%CI,1.18~10.41);而CYP1A1(Val/Val)/GSTM1(-)基因型个体患肺癌的风险度最高,OR为10.5(95.0%CI,1.70~64.73)。4)进一步分层分析发现,CYP1A1(Ile/Val+Val/Val)等位基因型主要增加鳞癌的危险性;而GSTM1基因型组织类型无明显的相关性。5)在分析吸烟对肺癌易感性的影响时发现,CYP1A1(Ile/Val+Val/Val)及GSTM1(-)等位基因型与吸烟有协同作用,并与至发病时的累积吸烟量有关。结论:CYP1A1(Val/Val  相似文献   

16.
目的:了解四川北部地区汉族肺癌人群GSTT1基因多态性状况,与其他地区人群人种进行比较。方法:采用聚合酶链式反应(PCR)技术检测该地区肺癌患者GSTT1基因缺失〔GSTT1(-)〕频率。结果:本地区肺癌患者GSTT1(-)频率为45%(45/100),其中纯和缺失率女性和男性分别为52.0%(13/25)和42.7%(32/75),χ2=0.660,P=0.417;鳞癌38.1%(16/42),腺癌48.0%(12/25),χ2=0.632,P=0.427;吸烟者44.4%(28/63),不吸烟者45.9%(17/37),χ2=0.021,P=0.884。结论:本地区肺癌患者GSTT1基因缺失频率高于欧美,与亚洲多中心研究结果类似,缺失频率与性别、病理类型及是否吸烟无关。  相似文献   

17.
目的 探讨谷胱苷肽硫转移酶M1(GSTM1)基因多态性与川北地区汉族人群肺癌易感性的关系。方法 采用病例对照研究和聚合酶链式反应(PCR)技术检测川北地区125例肺癌患者(肺癌组)和125例非肿瘤患者(对照组)GSTM1基因缺失型的频率,评价其与肺癌易感性的关系。结果 GSTM1缺失基因型[GSTM1(-)]频率在肺癌组和对照组分别为58.4%和56.8%,差异无统计学意义(=0.822);GSTM1(-)基因型与肺鳞癌(OR=0.97,95%CI:0.52~1.83,=0.934)和腺癌(OR=0.94,95%CI:0.42~2.04,=0.844)风险亦无明确关系。结论 GSTM1各基因型与肺癌风险无明确关系。  相似文献   

18.
Background/Aims: Glutathione S-transferase M1 (GSTM1) is a multifunctional enzyme that plays a criticalrole in the detoxification of varieties of carcinogenic metabolites. Many studies have been conducted to investigatethe association between GSTM1 polymorphism and nasopharyngeal cancer (NPC) risk, but the findings amongthose studies are inconsistent. To assess this relationship more precisely, we performed a meta-analysis of allavailable studies on the subject. Methods: Case-control studies were identified by searching Pubmed, Embase,ISI Web of Science, and Wanfang databases through September 6, 2012. We used the pooled odds ratio (OR)with its corresponding 95% confidence interval (95%CI) to evaluate the association of GSTM1 polymorphismwith NPC susceptibility. Subgroup analyses by pathological types, sex and smoking status were performed tofurther identify the association. Results: Overall, 11 published studies with 1,513 cases and 2,802 controls werefinally included into this meta-analysis according to the inclusion criteria. Meta-analysis of total studies showedthat the null genotype of GSTM1 was significantly associated with increased risk of NPC, when comparing withthe non-null genotype (OR=1.51, 95%CI=1.33-1.72, POR<0.001). The association was still statistically significantin subgroup analysis of patients with nasopharyngeal squamous cell carcinoma (OR=1.73, 95%CI=1.24-2.42,POR=0.001). Males with the null genotype of GSTM1 were more likely to subject to NPC than females. Inaddition, the association between the null genotype of GSTM1 and NPC risk was strongest in individuals withexposure to smoking. Sensitivity analysis by sequential omission of any individual studies one at a time furtherdemonstrated the significant association. Conclusions: The findings suggest that the null genotype of GSTM1 isa risk factor for NPC, and there is a gene- smoking interaction in this association  相似文献   

19.
BackgroundWe investigated whether genetic polymorphisms in the glutathione S transferase mu (GSTM1) and theta (GSTT1) genes modulated risk, disease progression and survival in primary muscle invasive bladder cancer (MIBC).MethodsGSTM1 and GSTT1 polymorphisms were analysed by multiplex polymerase chain reaction (PCR) using blood genomic DNA in 110 MIBC patients and 220 gender- and age-matched healthy controls. The influence of the genetic polymorphisms on patient survival was evaluated by Kaplan–Meier survival curves and Cox Proportional Hazard models. We also evaluated whether cigarette smoking and treatment modality modified the association between genotype and prognosis.ResultsGSTM1-null individuals exhibited increased risk for MIBC and an association with cigarette smoking. GSTT1-null subjects showed significant disease progression and cancer-specific death. In the combined analysis, GSTT1-null genotype was an independent risk factor for disease progression and cancer specific death regardless of GSTM1 genotype. Significant differences in progression-free survival (PFS) and cancer-specific survival (CSS) were seen based on GSTT1 genotype. The survival impact of the GSTT1 genotype was only valid for smokers. The GSTT1-null genotype was an independent prognostic factor for shorter PFS in patients who received chemotherapy and those who did not undergo radical cystectomy. By multivariate Cox regression analysis, GSTT1-null genotype was a predictive factor for disease progression and cancer specific survival regardless of treatment modality.ConclusionsThe GSTM1-null genotype plays an important role in genetic susceptibility to MIBC and the GSTT1-null genotype is associated with disease progression and shorter survival in MIBC.  相似文献   

20.
Background: Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphicgenes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which areinvolved in the bioactivation and detoxification of environmental toxins. This might be a factor in the variation inlung cancer incidence with ethnicity. Materials and Methods: We conducted a case-control study of 218 northernIndian lung cancer patients along with 238 healthy controls, to assess any association between CYP1A1, GSTM1and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of Lungcancer in our population. Results: We observed a significant difference in the GSTT1 null deletion frequency in thispopulation when compared with other populations (OR=1.87, 95%CI: 1.25-2.80–0.73, P=0.002). However, GSTM1null genotype was found associated with lung cancer in the non-smoking subgroup. (P=0.170). Conclusions: Ourstudy showed the GSTT1 null polymorphism to be associated with smoking-induced lung cancer and the GSTM1null polymorphism to have a link with non-smoking related lung cancer.  相似文献   

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