Lack of Assocation of Glutathione S-transferase T1 Gene Null and Susceptibility to Lung Cancer in China: a Meta-analysis

Background: Variation in metabolic genes is regarded as an important factor in processes leading to cancer.However, the effect of GSTT1 null genotype is divergent in the form of lung cancer. Methods: Studies wereconducted at different research databases from 1990 to 2013 and the total odds ratio (OR) and 95% confidenceinterval (CI) were calculated for lung cancer. Review Manager 5.2 and STATE 12 are employed. Results: TotalOR value is calculated from 17 articles with 2,118 cases and 2,915 controls. We discovered no significant increasein lung cancer risk among subjects carrying GSTT1 null genotype [OR = 1.15; 95% CI 0.97-1.36] in this metaanalysis.Conclusion: The GSTT1 deletion polymorphism does not have a significant effect on the susceptibilityto lung cancer overall in China.     

An updated pooled analysis of glutathione S-transferase genotype polymorphisms and risk of adult gliomas

Objective: Glutathione S-transferases (GSTs) are multifunctional enzymes that play a crucial role in thedetoxification of both the endogenous products of oxidative stress and exogenous carcinogens. Recent studiesinvestigating the association between genetic polymorphisms in GSTs and the risk of adult brain tumors havereported conflicting results. The rationale of this pooled analysis was to determine whether the presence of aGST variant increases adult glioma susceptibility by combining data from multiple studies. Methods: In ourmeta-analysis, 12 studies were identified by a search of the MEDLINE, HIGHWIRE, SCIENCEDIRECT andEMBASE databases. Of those 12, 11 evaluated GSTM1, nine evaluated GSTT1 and seven evaluated GSTP1Ile105Val. Between-study heterogeneity was assessed using χ2-based Q statistic and the I2 statistic. Crude oddsratios (ORs) with corresponding 95% confidence intervals (CIs) were used to estimate the association betweenGSTM1, GSTT1 and GSTP1 polymorphisms and the risk of adult gliomas. Results: The quantitative synthesisshowed no significant evidence to indicate an association exists between the presence of a GSTM1, GSTT1 orGSTP1 Ile105Val haplotype polymorphism and the risk of adult gliomas (OR, 1.008, 1.246, 1.061 respectively;95% CI, 0.901-1.129, 0.963-1.611, 0.653-1.724 respectively). Conclusions: Overall, this study did not suggestany strong relationship between GST variants or related enzyme polymorphisms and an increased risk of adultgliomas. Some caveats include absence of specific raw information on ethnic groups or smoking history onglioma cases in published articles; therefore, well-designed studies with a clear stratified analysis on potentialconfounding factors are needed to confirm these results.     

Ⅱ相代谢酶基因多态性与广西肝癌发生的关系

目的　探讨Ⅱ相代谢酶谷胱甘肽硫转移酶M 1、T 1(GSTM 1、GSTT1)及微粒体环氧化物水解酶 (mEH )基因多态性与广西肝癌易感性的关系 ,以及基因与基因间的相互作用。方法　采用多重PCR、PCR RFLP技术 ,对广西地区 10 5例肝癌患者及 15 1例健康对照的GSTM 1、GSTT 1、mEH基因型进行检测。结果　GSTM 1基因缺失率在病例组与对照组中分别为 64 .76%和5 0 .99% ,两者比较有显著性差异 (P <0 .0 5 ,OR =1.77) ;病例组GSTT 1基因缺失率 (4 0 .95 % )高于对照组 (3 3 .11% ) ,mEH 3种基因型频率在病例组分别为 2 7.62 %、2 1.90 %、5 0 .48% ,对照组则分别为 2 1.19%、3 4.44 %、44 .3 7% ,两组比较无显著性差异 (P >0 .0 5 ) ;GSTM 1、T 1基因同时缺失的个体患肝癌的危险性增大了 1.2 2倍。结论　GSTM 1、T1基因同时缺失是肝癌的易感因素 ,可作为肝癌高危人群筛选的标记物。     

ＧＳＴＭ１基因多态性与川北地区肺癌易感性关系的研究

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（Ｐ＝０.８２２）;ＧＳＴＭ１（－）基因型与肺鳞癌（ＯＲ＝０.９７,９５％ＣＩ：０.５２～１.８３,Ｐ＝０.９３４）和腺癌（ＯＲ＝０.９４,９５％ＣＩ：０.４２～２.０４,Ｐ＝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。     

Glutathione S-Transferase P1 Variant Plays a Major Contribution to Decreased Susceptibility to Liver Cancer in Thais

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.     

Meta-analysis of the association between GSTM1 and GSTT1 gene polymorphisms and cervical cancer

Aim: We conducted a meta-analysis to analyze the influence of GSTM1 and GSTT1 gene polymorphisms on cervical cancer risk, and explore gene-environment interactions. Methods: Identification of relevant studies was carried out through a search of Medline and the EMbase up to Oct. 2011. All case-control studies that investigated the association between GSTM1 and GSTT1 gene polymorphisms and risk of cervical cancer were included. The pooled odds ratio (OR) was used for analyses of results and the corresponding 95% confidence intervals (CI) were estimated. Results: A total of 21 case-control studies were included in the meta-analysis of GSTM1 (2,378 cases and 2,639 controls) and GSTT1 (1,229 cases and 1,223 controls) genotypes. The overall results showed that the GSTM1 null was related to an increased risk of cervical cancer (OR=1.50, 95% CI=1.21-1.85). Subgroup analysis were performed based on smoking and ethnicity. Our results showed that smokers with null GSTM1 genotype had a moderate increased risk of cervical cancer (OR=1.85, 95% CI=1.07-3.20). For the ethnicity stratification, moderate significantly increased risk of null GSTM1 genotype was found in Chinese (OR=2.12, 95% CI=1.43-3.15) and Indian populations (OR=2.07, 95% CI=1.49-2.88), but no increased risk was noted in others. Conclusion: This meta-analysis provided strong evidence that the GSTM1 genotype is associated with the development of cervical cancer, especially in smokers, and Chinese and Indian populations. However, no association was found for GSTT1 null genotype carriers.     

Null Glutathione S-transferase T1 and M1 Genotypes and Oral Cancer Susceptibility in China and India - a Meta-analysis

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.     

Meta-analysis of GSTM1 and GSTT1 Polymorphisms and Riskof Nasopharyngeal Cancer

Background: Studies of associations between genetic polymorphism of glutathione S-transferase M1 (GSTM1)and glutathione S-transferase T1 (GSTT1) with risk of nasopharyngeal cancer (NPC) have generated conflictingresults. Thus, a meta-analysis was performed to clarify the effects of GSTM1 and GSTT1 polymorphisms on therisk of developing NPC. Materials and Methods: A literature search in two electronic databases namely PubMedand EMBASE up to December 2012 was conducted and eligible papers were finally selected based on the inclusionand exclusion criteria. The pooled odds ratio (OR) and presence of heterogeneity and publication bias in thosestudies were evaluated. Results: A total of 9 studies concerning nasopharyngeal cancer were evaluated. Analysesof all relevant studies showed increased NPC risk to be significantly associated with the null genotypes of GSTMI(OR=1.43, 95%CI 1.24-1.66) and GSTT1 (OR=1.28, 95%CI=1.09-1.51). In addition, evidence of publication biaswas detected among the studies on GSTM1 polymorphism. Conclusions: This meta-analysis demonstrated theGSTM1 and GSTT1 null genotypes are associated with an increased risk of NPC.     

Glutathione S-Transferase Polymorphisms in Breast Cancers of Thai Patients

Breast cancer is the most common cancer among women worldwide and second in Thailand. Glutathione Stransferase(GST) enzymes involved in the detoxification of reactive metabolites of carcinogens may be importantin modulating susceptibility to cancers. This study aimed to determine the influence of genetic polymorphismsof glutathione S-transferase T1, M1, P1 and A1 on breast cancer in Thai patients. Links with clinico-pathologicalcharacteristics were also analyzed. The results showed no association between GSTs polymorphism and overallsusceptibility to breast cancer in Thai patients (P ≥ 0.05). However, the data pointed to a relation of theGSTP1(Ile105Val) polymorphism with progesterone receptor status (P = 0.04) and age at diagnosis (P = 0.03) ofbreast cancer cases. In summary, this is the first study to report association between glutathione S-transferaseT1, M1, P1 and A1 genes polymorphism and breast cancer in Thai patients. While GST genotypes may not beassociated with susceptibility, a GSTP1 polymorphism(Ile105Val) may be related to progression of breast cancer.     

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.     

Polymorphism in GSTM1, GSTT1, and GSTP1 and Susceptibility to Lung Cancer in a Japanese Population

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.     

Lack of association between GSTM1 and GSTT1 polymorphisms and brain tumour risk

Objective: Glutathione S-transferases (GSTs) are important enzymes that are involved in detoxification ofenvironmental carcinogens. Molecular epidemiological studies have been conducted to investigate the associationbetween GSTM1 and GSTT1 homozygous deletion polymorphisms and brain tumours but results have beenconflicting. The aim of this study was to clarify this problem using a meta-analysis. Methods: A total of 9 recordswere identified by searching the PubMed and Embase databases. Fixed- and random-effects models wereperformed to estimate the pooled odds ratios. Results: No significant association was found between the GSTM1and GSTT1 homozygous deletion polymorphisms and risk of brain tumours, including glioma and meningioma.Similar negative results were also observed in both population-based and hospital-based studies. Conclusion:These findings indicate that the GSTM1 and GSTT1 polymorphisms may not be related to the development ofbrain tumours.     

Glutathione S-transferase M1 Null Genotype and Hepatocellular Carcinoma Susceptibility in China and India: Evidence from an Updated Meta-analysis

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.     

Glutathione-S-transferase (GSTM1, GSTT1) Null Phenotypes and Risk of Lung Cancer in a Korean Population

Purpose: The aim of this study was to evaluate any association of GSTM1 and GSTT1 null genotypes withthe risk of lung cancer in a South Korean population. Methods: We conducted a large-scale, population-basedcase-control study including 3,933 lung cancer cases and 1,699 controls. Genotypes of GSTM1 and GSTT1 weredetermined using real-time polymerase chain reaction. Results: In logistic regression analysis adjusted for age andsmoking, we did not find any association between GSTM1 or GSTT1 and LC risk in women. However, in men,the GSTM1 and GSTTI null genotypes were borderline associated with risk (OR=1.18, 95% CI=0.99-1.41 forGSTM1, OR=1.18, 95% CI=0.99-1.41 for GSTT1), and combined GSTM1 and GSTT1 null genotypes conferredan increased risk for LC in men (OR=1.39, 95% CI=1.08–1.78). The OR for the GSTT1 null genotype was greaterin subjects aged 55 years old or younger (OR=1.45, 95% CI=1.09-1.92 for men; OR=1.36, 95% CI=0.97–1.90for women), than in those over age 55 (OR=1.03, 95% CI=0.83-1.27 for men; OR=0.86, 95% CI=0.66–1.12 forwomen) in both genders (p for interaction <0.05). Conclusions: In the Korean population, the GSTM1 andGSTT1 null genotypes are risk factors for LC in men; the GSTT1 null genotype has a more prominent effecton LC risk in younger people (age 55 years and under) than in older individuals.     

四川北部地区肺癌患者GSTT1基因多态性分析

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。     

Polymorphisms of CYP1A1, GSTM1, GSTT1, and prostate cancer risk in Turkish population

Prostate cancer is the most common cancer among men in many countries. Although the etiology of prostate cancer largely is unknown, both genetic and environmental factors may be involved. Advanced age, androgen metabolism, and heredity-race have been reported to be possible risk factors. On the other hand, several studies indicate that genetic polymorphisms in biotransformation enzymes play a role in prostate cancer development. In this study, association of the prostate cancer risk with genotype frequencies of the Phase I (CYP1A1) and Phase II (GSTM1 and GSTT1) biotransformation enzymes was investigated in 321 Turkish individuals (152 prostate cancer patients and 169 age-matched male controls). The presence or absences of the GSTM1 and GSTT1 genes were determined by a PCR-based method. Genotypes of CYP1A1 were determined by MspI-RFLP. The prevalence of GSTM1 null genotype in the cases was 64 percent, compared to 31 percent in the control group, indicating a strong association (OR = 4.08, 95%CI = 2.50-6.69). No association was observed between either GSTT1 null genotype or CYP1A1 polymorphism and prostate cancer incidence. No statistically significant association was observed between smoking status of the patients and any of the polymorphisms studied. In conclusion, results of this study indicate that only the GSTM1 null genotype may play an important role as a risk factor for prostate cancer development in Turkish population.     

Allelic Variation of GSTT1, GSTM1 and GSTP1 Genes in a North Indian Population

Glutathione S-transferase (GST) enzymes are involved in detoxification of many potentially carcinogenic ‍compounds. Homozygous deletions or null genotypes of GSTT1 and GSTM1 genes and an A to G substitution at ‍nucleotide 313 in GSTP1 have been reported in different populations. Intra-ethnic as well as interethnic differences ‍are known to exist in the frequencies of the above GST genes. The present study was therefore undertaken to ‍determine the prevalence of GSTM1 and GSTT1null alleles, as well as the GSTP1 gene polymorphism, in 370 ‍healthy individuals in a North Indian population. Genotyping of M1 and T1 was performed using a multiplex ‍polymerase chain reaction and the GSTP1 polymorphism was determined by the polymerase chain reaction/restriction ‍fragment length polymorphism (PCR-RFLP) method. The frequencies of GSTM1 and GSTT1 null alleles in normal ‍healthy individuals were observed to be 33.0% and 18.4% respectively. In 7.0% of individuals’ concomitant lack of ‍M1 and T1 genes were observed. For GSTP1, wild (Ile/Ile), heterozygous (Ile/Val) and mutant (Val/Val) genotypes ‍were observed for 44.3%, 50.3% and 5.4% of individuals respectively. The prevalence of the M1 null allele is ‍significantly lower than those documented for English, Turkish, Chinese, Caucasians, Japanese and white (Brazilian ‍and American) populations. However, a significantly higher frequency for T1 null was reported in Chinese and ‍Japanese population. Furthermore, Japanese and African American populations have exhibited significantly higher ‍frequencies of wild and mutant P1 genotypes, respectively, than the Indian population. Thus, our results signify an ‍impact of ethnicity and provide a basis for future epidemiological and clinical studies.     

Genetic Polymorphisms of GSTM1 and GSTT1 Genes in Delhi and Comparison with other Indian and Global Populations

The glutathione S-transferases (GSTs) are involved in the metabolism of many xenobiotics, including an arrayof environmental carcinogens, pollutants, and drugs. Genetic polymorphisms in these genes may lead to interindividualvariation in susceptibility to various diseases. In the present study, GSTM1 and GSTT1 polymorphismswere analysed using a multiplex polymerase chain reaction in 500 normal individuals from Delhi. The frequencyof individuals with GSTM1 and GSTT1 null genotypes were 168 (33.6%) and 62 (12.4%) respectively, and54(10.8%) were having homozygous null genotype for both the genes GSTM1 and GSTT1simultaneously. Thestudied population was compared with reported frequencies from other neighbouring state populations, aswell as with those from other ethnic groups; Europeans, Blacks, and Asians. The prevalence of homozygousnull GSTM1 genotype is significantly higher in Caucasians and Asians as compared to Indian population. Thefrequency of GSTT1 homozygous null genotypes is also significantly higher in blacks and Asians. We believethat due to large number of individuals in this study, our results are reliable estimates of the frequencies of theGSTM1, GSTT1 in Delhi. It would provide a basic database for future clinical and genetic studies pertaining tosusceptibility and inconsistency in the response and/or toxicity to drugs known to be the substrates for GSTs.     

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...