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.     

Glutathione S-transferase T1 null-genotype is associated with an increased risk of lung cancer

Glutathione S-transferases (GSTs) are involved in detoxification of carcinogens, e.g., from tobacco smoke. Therefore, polymorphisms in the GST genes have been considered as potential modifiers of individual cancer risk. In a population-based case-cohort study where cases and the subcohort sample were matched on duration of smoking, we investigated the occurrence of lung cancer and histological subtypes of lung cancer in relation to deletion polymorphism in both GSTM1 and GSTT1, single nucleotide polymorphisms (SNPs) in GSTP1 (Ile105Val and Ala114Val) and a 3 base pair deletion polymorphism in GSTM3. We further investigated the effects of the GST polymorphisms on lung cancer risk within subgroups of subjects defined by gender and age. The results showed a 2.4-fold (CI = 1.31-4.41) increased risk of lung cancer in GSTT1 null-genotype carriers but no significant effects of the polymorphisms in GSTM1, GSTM3, GSTP1-105 or GSTP1-114. The association was strongest in lower age groups, with a 9.6-fold increase in risk for subjects with the GSTT1 null-genotype in the 50-55 years age interval (CI = 3.03-30.59). Positive associations were found for GSTT1 within all major histological subtypes. Squamous cell carcinoma was the histological type most strongly associated with the GSTT1 genotype, with a 5.0-fold (CI = 2.26-11.18) increase in risk for subjects carrying the GSTT1 null-genotype. The effects of the GSTT1 null-genotype seemed stronger in the presence of the GSTM1 null-genotype or the GSTP1-105 variant allele. These results suggest that the GSTT1 null-genotype is associated with an increased risk of lung cancer, especially in younger individuals.     

Genetic polymorphism of glutathione S-transferase P1 gene and lung cancer risk

Objectives: The human GSTTP1 gene is polymorphic with an A G transition in exon 5 causing a replacement 105 IleVal in the GSTP1 protein. The two isoforms, encoded by the alleles GSTP1*A and GSTP1*B, respectively, show different catalytic efficiencies towards some carcinogenic epoxides. In this study we have addressed the possible role of the Ile105Val GSTP1 polymorphism in lung cancer susceptibility.Methods: The polymorphic site was genotyped by RFLP in a group of lung cancer patients (n=164) and in two control groups (healthy smokers, n=132; general population, n=200). All patients and controls were Northwestern Mediterranean Caucasians of the same ethnic origin.Results and Conclusions: The cancer patients showed frequencies of GSTP1*A/A; GSTP1*A/B and GSTP1*B/B (50%, 38%, 11%, respectively) very similar to those of both control groups (healthy smokers: 48%, 41%, 11%). After adjusting for age, sex and smoking status, no association was found between the GSTP1*B allele and lung cancer risk (OR: 1.18; 95% CI: 0.67–2.07). The Ile105val GSTP1 polymorphism was also analysed in combination with the GSTM1 and GSTT1 genes. The results showed that allelism at GSTP1 did not increase the risk associated with the GSTM1 or GSTT1 deletions.     

Association between a glutathione S-transferase A1 promoter polymorphism and survival after breast cancer treatment

Glutathione S-transferase (GST) enzymes detoxify chemotherapeutic drugs, and several studies have reported differences in survival for cancer patients who have variant genotypes for GSTP1, GSTM1 or GSTT1 enzymes. A recently described polymorphism alters hepatic expression of GSTA1, a GST with high activity in glutathione conjugation of metabolites of cyclophosphamide (CP). To consider the possible influence of the reduced-expression GSTA1*B allele on cancer patient survival, we have conducted a pilot study of breast cancer patients treated with CP-containing combination chemotherapy. GSTA1 genotype was determined by polymerase chain reaction and restriction fragment length polymorphism. Kaplan-Meier methods and Cox proportional hazards models were used to evaluate survival in relation to genotype. Among 245 subjects, 35% were GSTA1*A/*A, 49% GSTA1*A/*B and 16% GSTA1*B/*B; the genotype distribution did not differ by ethnic group, age or stage at diagnosis. Among patients who had 0 or 1 GSTA1*B allele, the proportion surviving at 5 years was 0.66 (95% CI = 0.59-0.72), whereas for GSTA1*B/*B subjects the proportion was higher, 0.86 (95% CI = 0.67-0.95). Significantly reduced hazard of death was observed for GSTA1*B/*B subjects during the first 5 years after diagnosis, hazard ratio (HR) = 0.3, 95% CI = 0.1-0.8. The association varied with time, with no survival difference observed for subjects who survived beyond 5 years. These results, although based on a small study population, describe an apparent difference in survival after treatment for breast cancer according to GSTA1 genotype. Further studies should consider the possible association between the novel GSTA1*B variant and outcomes of cancer therapy.     

Association between somatostatin receptor 5 gene polymorphisms and pancreatic cancer risk and survival

BACKGROUND:

Somatostatin (SST) inhibited cell proliferation and negatively regulated the release of growth hormones by means of specific receptors (SSTR). Genetic variation in SSTR had been associated with risk of human cancers but had never been investigated in pancreatic cancer.

METHODS:

In this retrospective study the SSTR5 gene in paired tumor and blood samples from 33 pancreatic adenocarcinoma patients using the Sanger method were sequenced. Three single nucleotide polymorphisms (SNPs) in samples from 863 patients with pancreatic ductal adenocarcinoma and 876 healthy controls using the TaqMan method were analyzed. The associations between gene polymorphisms and pancreatic cancer risk and survival were analyzed by multivariate logistic regression and Cox proportional hazard models, respectively.

RESULTS:

No somatic mutations were identified, but 3 nonsynonymous SSTR5 SNPs (P109S, L48M, and P335L) in pancreatic tumors were identified. The SSTR5 P109S variant allele was associated with a 1.62‐fold increased risk of pancreatic cancer (95% confidence interval [CI]: 1.08‐2.43, P = 0.019). Furthermore, the SSTR5 L48M AC variant and smoking had a joint effect on pancreatic cancer risk (p_interaction = 0.035). The odds ratios (95% confidence intervals) were 0.58 (0.34‐0.97), 1.49 (1.18‐1.89), and 2.27 (1.35‐3.83) for the variant genotype alone, smoking alone, and both factors, respectively, compared with no factors. Finally, SSTR5 P335L CC and P109S CC combined were associated with lower overall survival durations in patients with resectable disease.

CONCLUSIONS:

These data suggest that SSTR5 genetic variants play a role in pancreatic cancer development and progression. Cancer 2011. © 2011 American Cancer Society.     

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.     

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.     

Effects of base excision repair gene polymorphisms on pancreatic cancer survival

To explore the association between single nucleotide polymorphisms of DNA repair genes and overall survival of patients with pancreatic cancer, we conducted a study in 378 cases of pancreatic adenocarcinoma who were treated at The University of Texas M. D. Anderson Cancer Center between February 1999 and October 2004 and were followed up to April 2006. Genotypes were determined using genomic DNA and the MassCode method. Overall survival was analyzed using the Kaplan-Meier plot, log-rank test and Cox regression. We observed a strong effect of the POLB A165G and T2133C genotypes on overall survival. The median survival time (MST) was 35.7 months for patients carrying at least 1 of the 2 homozygous variant POLB GG or CC genotypes, compared with 14.8 months for those carrying the AA/AG or TT/TC genotypes (p = 0.02, log rank test). The homozygous variants of hOGG1 G2657A, APEX1 D148E and XRCC1 R194W polymorphisms all showed a weak but significant effect on overall survival as demonstrated by either log rank test or multivariate COX regression after adjusting for other potential confounders. In combined genotype analysis, a predominant effect of the POLB homozygous variants on survival was observed. When POLB was not included in the model, a slightly better survival was observed among those carrying none of the adverse genotypes than those carrying at least one of the adverse genotypes. These observations suggest that polymorphisms of base excision repair genes significantly affect the clinical outcome of patients with pancreatic cancer. These observations need to be confirmed in a larger study of homogenous patient population.     

谷胱甘肽硫转移酶M1基因多态性与食管癌Meta分析

[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。     

Glutathione S‐transferase polymorphisms are associated with survival in anaplastic glioma patients

BACKGROUND:

Glutathione S‐transferases (GSTs) are polymorphic enzymes that are responsible for glutathione conjugation of alkylators and scavenging of free radicals created by radiation. GST polymorphisms may result in altered or absent enzyme activity and have been associated with survival in patients with cancer. The authors of this report hypothesized that patients with anaplastic glioma (AG) who have GST genotypes that encode for lower activity enzymes will have longer survival than similar patients who have higher activity genotypes. The current study was performed to investigate the role of GST enzyme polymorphisms in predicting the survival of patients with AG.

METHODS:

The medical records of 207 patients with AG from a single cancer center were reviewed retrospectively. Polymorphisms for the GST μ1 (GSTM1), GST θ1 (GSTT1), and GST π1 (GSTP1) enzymes were identified. Overall survival was compared using the Kaplan‐Meier method and Cox proportional hazards analyses adjusting for age, sex, histology, and therapy.

RESULTS:

Among the patients with oligodendroglial tumors (n = 94), patients who had the GSTT1 null genotype had a 2.9 times increased risk of death (95% confidence interval [CI], 1.3‐6.3) compared with patients who had the GSTT1 non‐null genotype. Adjustment for 1p/19q status did not change the finding. In the patients who had anaplastic astrocytoma (n = 113), the patients with all GSTP1 genotypes except GSTP1 *B/*B had a 3.8 times increased risk of death (95% CI, 0.5‐29.6) compared with patients who had the GSTP1 *B/*B genotype.

CONCLUSIONS:

In patients with anaplastic oligodendroglial tumors, the GSTT1 null genotype may be associated with poor survival, possibly because of modifications in therapy secondary to increased toxicity. This hypothesis is under investigation. In patients with anaplastic astrocytoma, the GSTP1 *B/*B genotype may confer a survival advantage. Cancer 2010. © 2010 American Cancer Society.     

Glucose metabolism gene polymorphisms and clinical outcome in pancreatic cancer

BACKGROUND:

Altered glucose metabolism is the most common metabolic hallmark of malignancies. The authors tested the hypothesis that glucose metabolism gene variations affect clinical outcome in pancreatic cancer.

METHODS:

The authors retrospectively genotyped 26 single nucleotide polymorphisms from 5 glucose metabolism genes in 154 patients with localized disease and validated the findings in 552 patients with different stages of pancreatic adenocarcinoma. Association between genotypes and overall survival (OS) was evaluated using multivariate Cox proportional hazard regression models with adjustment for clinical predictors.

RESULTS:

Glucokinase (GCK) IVS1 + 9652C > T and hexokinase 2 (HK2) N692N homozygous variants were significantly associated with reduced OS in the training set of 154 patients (P < .001). These associations were confirmed in the validation set of 552 patients and in the combined dataset of all 706 patients (P ≤ .001). In addition, HK2 R844K variant K allele was associated with a better survival in the validation set and the combined dataset (P ≤ .001). When data were further analyzed by disease stage, glutamine‐fructose‐6‐phosphate transaminase (GFPT1) IVS14‐3094T>C, HK2 N692N and R844K in patients with localized disease and GCK IVS1 + 9652C>T in patients with advanced disease were significant independent predictors for OS (P ≤ .001). Haplotype CGG of GPI and GCTATGG of HK2 were associated with better OS, respectively, with P values of .004 and .007.

CONCLUSIONS:

The authors demonstrated that glucose metabolism gene polymorphisms affect clinical outcome in pancreatic cancer. These observations support a role of abnormal glucose metabolism in pancreatic carcinogenesis. Cancer 2011. © 2010 American Cancer Society.     

GSTT1 and GSTM1 polymorphisms and myelodysplastic syndrome risk: a systematic review and meta‐analysis

Glutathione‐S‐transferace polymorphisms may make hematopoietic lineage cells susceptible to genotoxicity following exposure to heavy metals or benzene. We conducted a systematic review and meta‐analysis to define the effect of GSTM1 and GSTT1 null polymorphisms on MDS risk. We searched the PubMed and SCOPUS databases to identify peer‐reviewed published case‐control studies investigating the association between GSTT1 and/or GSTM1 null genotypes and development of MDS. Between‐study heterogeneity was assessed using Cochran's Q statistic and the I² statistic. Odds ratios from individual studies were pooled using fixed and random effects models. Thirteen studies were considered eligible for the GSTT1 meta‐analysis (1471 cases, 1907 controls) and 10 were considered eligible for the GSTM1 meta‐analysis (1161 cases, 1668 controls). For the GSTT1 polymorphism, there was moderate between study heterogeneity (p_Q = 0.01; I² = 52.3%) and the null genotype was significantly associated with increased risk of MDS development, random effects OR = 1.43 (95% CI, 1.09–1.89); p = 0.01. For the GSTM1 polymorphisms there was moderate between‐study heterogeneity (p = 0.07; I² = 43.1%) and the random effects OR = 1.02 (95% CI, 0.82–1.28) was non‐significant (p = 0.85). The GSTT1 null genotype is a significant risk factor for MDS development. Gene‐environment interactions need to be further explored.     

Dietary intake of Cruciferous vegetables, <Emphasis Type="Italic">Glutathione S-transferase (GST)</Emphasis> polymorphisms and lung cancer risk in a Caucasian population

Objective: To evaluate possible interactions between dietary intake of cruciferous vegetables and the glutathione s-transferase mu and theta (GSTM1 and GSTT1) genotypes in lung cancer risk. Methods: Hospital-based case–control study of 716 Caucasian lung cancer cases and 939 spouse and friend controls conducted in Boston, Massachussetts between 1992 and 2000. Dietary intake was collected through a food frequency questionnaire and blood was obtained for genotyping. Logistic regression models were adjusted for age, gender, total calories and smoking variables. Results: Higher intakes of cruciferous vegetables reduced lung cancer risk among GSTM1 present individuals (odds ratio (OR) _{highest versus lowest tertile} = 0.61, 95% confidence interval (CI) = 0.39–0.95) but not among GSTM1 null individuals (OR _{highest versus lowest tertile} = 1.15, 95% CI = 0.78–1.68). We observed statistically significant interactions between GSTM1 and cruciferous vegetable intake overall (likelihood ratio test (LRT): p = 0.05) and among current smokers (LRT: p = 0.01). No significant interactions were observed for GSTT1 or the combined GSTM1/T1 genotype. Conclusions: In our study, higher cruciferous vegetable intake reduced lung cancer risk only among individuals with the GSTM1 present genotype. Our findings differed from prior studies that specifically assessed isothiocyanates found in cruciferous vegetables or evaluated Asian study populations with higher levels of cruciferous vegetable consumption.     

Association between polymorphisms in the GSTA4 gene and risk of lung cancer: a case-control study in a Southeastern Chinese population

GST Alpha 4 (GSTA4) has an important role in the protection against oxidative stress induced by carcinogens such as tobacco smoke. However, few studies investigated the association between GSTA4 polymorphisms and lung cancer risk. We genotyped three selected GSTA4 SNPs (rs182623 - 1718:T > A, rs3798804 + 5034:G > A and rs316141 + 13984:C > T) in a case-control study of 500 lung cancer patients and 517 cancer-free controls and evaluated the association between these SNPs and risk of lung cancer in this Han Chinese population. We found that there was a significant difference in genotype and allele frequency distributions of GSTA4 -1718 between the cases and the controls (P = 0.006 and P = 0.003, respectively). Compared with the GSTA4 -1718TT genotype, individuals with the TA + AA genotypes had a significantly decreased risk of lung cancer (adjusted OR, 0.63; 95% CI, 0.47-0.84; P = 0.006). Although there were no such statistical differences between the cases and controls at the loci +5034 and +13984, nor for histological types, individuals carrying the genotypes of -1718TA, +5034GG and +13984CT had a significantly decreased lung cancer risk (OR, 0.37; 95% CI, 0.23-0.61; P < 0.0001), especially for those smokers who smoked 相似文献   

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) Polymorphisms and Lung Cancer Risk among a Select Group of Iranian People

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.     

Lack of influence of glutathione S-transferase gene deletions in sporadic breast cancer in Pakistan

Glutathione S-transferases constitute the phase II detoxification enzymes involved in the metabolism and detoxification of a wide range of potential environmental carcinogens. GSTM1 and GSTT1 are polymorphic and their deletions have been found to be associated with breast cancer risk in some of the world populations. The current study was aimed at evaluation of GSTM1 and GSTT1 gene deletions in 150 unrelated breast cancer patients and 150 healthy controls from Pakistani population. Multiplex PCR assay along with CYP1A1 exon 7 as an internal control was used. Our sampled patients and controls had a mean age of 48 (+11.8) and 45 (+7.9) years respectively. The analysis suggested that only 2% breast cancer patient and 8% controls had homozygous GSTM1 gene deletions (OR 0.23, 95% CI 0.06-0.85). A total of 8.7% patients and 18.6% controls had homozygous GSTT1 deletion (OR 0.41, 95% CI 0.25-0.83). The statistical analysis suggest that a non significant number (P>0.05) of individuals compared to controls have GSTM1 and GSTT1 gene deletions. Deletion in both genes was not observed in any of the patients or controls. The present case control study suggests no association of GSTM1 and GSTT1 gene deletions with sporadic form of breast cancer in Pakistani population.     

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.     

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.     

中国南方粤语方言地区汉族人群GSTM1、GSTT1基因多态性

背景与目的:了解谷胱甘肽-S-转移酶M1、T1(GSTM1、GSTT1)基因多态性在中国南方粤语方言地区健康人群中的分布规律,初步探讨其与人群某些疾病家族史之间的关系。材料与方法:根据研究目的在广东省新兴县和广东省广州市两个地区选择符合条件的健康人群606人作为研究对象。应用聚合酶链式反应-2%琼脂糖凝胶电泳的方法检测调查对象GSTM1、GSTT1基因型。结果:在调查人群中,GSTM1基因纯合缺失基因型GSTM1(-/-)的出现频率为56.8%(n=597);GSTT1基因纯合缺失基因型GSTT1(-/-)的出现频率为42.1%(n=579);两基因联合缺失的频率为22.8%(n=570)。结论:GSTM1与GSTT1基因之间在人群中分布相互独立,无连锁现象,GSTM1基因在两个不同地区来源人群中的分布有显著差异。GSTT1在人群中不同基因型的分布与研究人群中冠心病疾病家族史的发生之间显著关联,有冠心病家族史人群GSTT1缺失基因型的表达显著增加。     

Lack of Associations between Genetic Polymorphisms in GSTM1, GSTT1 and GSTP1 and Pancreatic Cancer Risk: A Multi-Institutional Case-Control Study in Japan

Background: We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizinggenes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. Materialsand Methods: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1,GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilicmolecules. The study population consisted of 360 patients and 400 control subjects, who were recruited fromseveral medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios(ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk.Results: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotypewas approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 andGSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated withthe risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-nullgenotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) forindividuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1-present genotypes. No synergistic effects of smoking or GST genotypes were observed. Conclusions: Our resultsindicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancerrisk in the Japanese subjects in our study.