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.     

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.     

Prognostic potential of glutathione S-transferase M1 and T1 null genotypes for gastric cancer progression

To improve understanding of glutathione S-transferase (GST) behavior in terms of a development and prognostic factor for gastric adenocarcinoma, we investigated the association between the GSTM1 and GSTT1 null genotypes and gastric cancer risk or the prognostic value of the GSTM1 and GSTT1 null genotypes was evaluated. Using a polymerase chain reaction-based method, the frequencies of GSTM1 and GSTT1 genotypes and prognostic factors, such as staging, differentiation, and histologic type (intestinal vs. diffuse), were evaluated in 80 patients with curatively resected primary gastric adenocarcinoma. The frequencies of GSTM1 and GSTT1 null individuals were higher in the gastric cancer group, but the differences were not statistically significant (for GSTM1 null odds ratio (OR)=0.86; 95% confidence interval (CI)=0.49-1.51 and for GSTT1, OR=0.97; 95% CI=0.55-1.71). Since the GSTM1 and GSTT1 null genotypes are potential indicators of gastric adenocarcinoma, we examined the relationship between the GSTM1 and GSTT1 genotypes and prognostic factors. In terms of the histologically diffuse type of cancer, GSTM1 indicated an approximately 3.24-fold increase (OR=3.24; 95% CI=1.05-10.17). With respect to gastric cancer differentiation, the frequency of the GSTM1 null genotype was linked with a statistically significant increase in risk (3.42-fold) for the high-grade type (OR=3.42; CI=1.02-13.24). Our results indicate that there is no obvious relationship between GSTM1 and GSTT1 polymorphisms and the development of gastric cancer. However, in Korean gastric adenocarcinoma patients the GSTM1 null genotype appears to be associated with a poorer prognosis.     

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.     

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.     

Glutathione S-transferase M1 and T1 Polymorphisms,Cigarette Smoking and HPV Infection in Precancerous and Cancerous Lesions of the Uterine Cervix

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles.The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned toevaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. Thestudy was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minorgynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attendingthe cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) usingL1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures.Differences in proportions were tested using Pearson’s Chi-square test with Odds ratio (OR) and 95% confidenceinterval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype(OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes wasobserved in women with normal, precancerous and cervical cancerous lesions among ≤35 or >35 years of agegroups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers(OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervicalcancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) andGSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive nonsmokers. The results demonstrate that the GST null genotypes were alone not associated with the developmentof cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.     

GSTM1 and GSTT1 Genetic Polymorphisms and Breast Cancer Risk in Selected Filipino Cases

Background: The association of genetic polymorphisms with cancer development has been shown to be race- andtumor site-specific. Thus, this study aimed to determine whether polymorphisms in the GSTM1 and GSTT1 genesare associated with breast cancer among selected Filipinos. Methods: A total of 136 histologically confirmed breastcancer cases were age- and sex-matched with 136 clinically healthy controls. Genomic DNA extracted from bloodsamples of participants were screened for GSTM1 and GSTT1 genetic polymorphisms by multiplex PCR. Results:The frequency of null genotypes among the cases (GSTM1: n=78; 57.4%; GSTT1: n=61; 44.9%) was not significantlydifferent (p>0.05) from the controls (GSTM1: n=93; 68.4%; GSTT1: n=59; 43.4%). It was also demonstrated that riskfor breast cancer was increased in passive smokers carrying the GSTM1 null (OR=2.56; 95% CI=1.38-4.75) or GSTT1positive (OR=2.00; 95% CI=1.05-3.83) genotypes. Moreover, risk was decreased in alcohol users carrying the GSTT1null (OR=0.39; 95% CI=0.16-0.97) genotype. Conclusion: This study suggests that variants of GSTM1 and GSTT1may not be risk factors for breast cancer development among Filipinos. However, the risk may be increased when thesegenotypes were combined with lifestyle or environmental factors.     

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

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

Glutathione S-transferase M3 (A/A) genotype as a risk factor for oral cancer and leukoplakia among Indian tobacco smokers

Polymorphism in glutathione S-transferase (GST) genes, causing variations in enzyme activities, may influence susceptibility to oral cancer and leukoplakia in smokers and/or smokeless tobacco users. In this case-control study consisting of 109 leukoplakia and 256 oral cancer patients and 259 controls, genotype frequencies at GSTM1, GSTT1, GSTM3 and GSTP1 loci were determined by polymerase chain reaction-restriction fragment length polymorphism methods and analyzed by multiple logistic regression to determine the risks of the diseases. There were no significant differences in the distributions of GSTM1, GSTM3 and GSTT1 genotypes in patients and controls when all individuals were compared. In contrast, frequencies of ile/ile genotype at codon 105 and variant val-ala haplotype of GSTP1 was significantly higher (OR = 1.5; 95% CI = 1.0-2.0) and lower (OR = 1.4; 95% CI = 1.0-1.9) in oral cancer patients compare to controls, respectively. The impacts of all genotypes on risks of oral cancer and leukoplakia were also analyzed in patients with different tobacco habits and doses. Increased risks of cancer and leukoplakia were observed in tobacco smokers with GSTM3 (A/A) genotype (OR = 2.0, 95% CI = 1.0-4.0; OR = 2.0, 95% CI = 1.0-4.4, respectively). So, GSTM3 (A/A) genotype could become one of the markers to know which of the leukoplakia would be transformed into cancer. Heavy tobacco chewing (> 124 chewing-year) increased the risk of cancer in individuals with GSTT1 homozygous null genotype (OR = 3.0; 95% CI = 1.0-9.8). Furthermore, increased lifetime exposure to tobacco smoking (> 11.5 pack-year) increased the risk of leukoplakia in individuals with GSTM1 homozygous null genotype (OR = 2.4; 95% CI = 1.0-5.7). It may be suggested that polymorphisms in GSTP1, GSTM1, GSTM3 and GSTT1 genes regulate risk of cancer and leukoplakia differentially among different tobacco habituals.     

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

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

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

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

Glutathione S-transferase mu and theta polymorphisms and breast cancer susceptibility

BACKGROUND: The enzymes encoded by the glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism (mainly inactivation, but activation is possible) of a wide range of carcinogens that are ubiquitous in the environment; the enzyme encoded by the GSTT1 gene may also be active in endogenous mutagenic processes. Homozygous deletions of the GSTM1 and GSTT1 genes are commonly found in the population and result in a lack of enzyme activity. This study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and breast cancer risk. METHODS: Our study included 466 women with incident cases of breast cancer occurring from May 1989 through May 1994 and 466 matched control subjects. These individuals were part of a prospective cohort of U.S. women (i.e., the Nurses' Health Study). Odds ratios (ORs) and 95% confidence intervals (CIs) from conditional logistic regression models were used to estimate the association between genetic polymorphisms and breast cancer risk. RESULTS: The GSTM1 and GSTT1 null genotypes were not associated with an increased risk of breast cancer (OR = 1.05 [95% CI = 0.80-1.37] for GSTM1 null; OR = 0. 86 [95% CI = 0.61-1.21] for GSTT1 null). On the contrary, a suggestion of a decreased risk of breast cancer associated with the GSTT1 null genotype was observed among premenopausal women. When considered together, no combination of the GSTM1 and GSTT1 genotypes was associated with an increased risk of breast cancer. The relationship between GSTM1 and GSTT1 gene deletions and breast cancer risk was not substantially modified by cigarette smoking. CONCLUSIONS: Our data provide evidence against a substantially increased risk of breast cancer associated with GSTM1 and/or GSTT1 homozygous gene deletions.     

GSTM1、GSTT1基因多态性和吸烟与膀胱癌关系的病例对照研究

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

GSTT1 and GSTM1 null genotypes and the risk of gastric cancer: a case-control study in a Chinese population.

Glutathione S-transferase (GST) enzymes are involved in detoxification of many potentially carcinogenic compounds. The homozygous deletions or null genotypes of GSTT1 (theta class) and GSTM1 (mu class) genes may be associated with an increased risk of cancer. Few studies have evaluated the relationship between GSTT1, GSTM1 and the risk of gastric cancer, as well as the potential interactions between these genetic markers and other risk factors of gastric cancer in the Chinese population. We conducted a case-control study with 143 cases with gastric cancer, 166 chronic gastritis (CG) cases and 433 cancer-free population controls from Yangzhong County, China. The epidemiological data were collected by a standard questionnaire for all of the subjects, and blood samples were obtained from 91 gastric cancer cases, 146 CG cases, and 429 controls. GSTT1 and GSTM1 genotypes were assayed by the PCR method, and Helicobacter pylori infection was measured by the ELISA method. Using logistic regression model in SAS, we assessed the independent effects of GSTT1 and GSTM1 null genotypes on the risk of gastric cancer and their potential interactions with other factors. The prevalence of GSTM1 null genotype was 48% in gastric cancer cases, 60% in CG patients, and 51% in controls. The prevalence of GSTT1 null genotype was 54% in gastric cancer cases, 48% in CG patients, and 46% in controls. After controlling for age, gender, education, pack-years of smoking, alcohol drinking, body mass index, H. pylori infection, and fruit and salt intake, the adjusted odds ratio (OR) for GSTT1 and gastric cancer was 2.50 (95% confidence interval (CI), 1.01-6.22). When gastric cancer cases were compared with CG patients, the adjusted OR for GSTT1 was 2.33 (95% CI, 0.75-7.25). However, GSTT1 null genotype was not associated with the risk of CG when using population controls. No obvious association was found between GSTM1 and the risk of both gastric cancer and CG. Our results suggest that GSTT1 null genotype may be associated with an increased risk of gastric cancer in a Chinese population.     

Gluthatione-S-transferase T1-null Genotype Predisposes Adults to Acute Promyelocytic Leukemia; a Case-Control Study

Polymorphisms of glutathione S-transferase (GST) proteins are correlated with elevated risk of many cancersincluding hematologic malignancies. Particularly concerning acute promyelocytic leukemia (APL), the studies onassociation between GSTM1, GSTT1 and GSTP1 and the disease predisposition are scarce and contradictory. Theaim of this study was to examine whether polymorphic variations in GST confer susceptibility to APL. GSTM1and GSTT1 null and GSTP1 Ile105Val alleles were determined using polymerase chain reaction (PCR) andPCR-RFLP, respectively, in 114 APL patients and 99 healthy controls. Frequency of GSTT1 null and GSTM1null genotypes were higher in APL group which it was statistically significant for GSTT1 null (p< 0.01). TheGSTM1 null and GSTT1 null conferred a 1.36-fold (OR= 1.36, 95% CI = 0.79-2.33, p= 0.18) and 2.14-fold (OR=2.14; 95% CI: 1.18-3.92, p= 0.013) increase in risk of APL, respectively, relative to the presence of the GSTM1 orGSTT1 genes. GSTP1 Ile105/Val105 and Val105/Val105 genotypes showed no increase in the risk of APL (OR=0.94; 95% CI: 0.52-1.67 and OR= 1.12; 95% CI: 0.48-2.60, respectively). Our results suggest that GSTT1 nullgenotype may be associated with increased risk of APL.     

GSTM1 and GSTT1 Polymorphisms and Susceptibility to Prostate Cancer: A Case-Control Study of the Algerian Population

Objective: Prostate cancer (PCa) is a major public health problem worldwide, with high morbidity and mortality levels. Advanced age, androgen stimulation, and ethnicity have been reported to be possible risk factors. It has been suggested that particular genetic polymorphisms in glutathione S-transferases (GST), xenobiotic-metabolising enzymes, could predispose to prostate cancer through heritable deficiency in detoxification of environmental carcinogens. Conflicts in the published results and the absence of similar in depth studies in Algeria prompted us to perform the present case-control study of GSTM1 and GSTT1 polymorphisms and their possible association with PCa in an Algerian population. Methods: We determined GSTM1 and GSTT1 genotypes for 49 histologically verified prostate cancer patients and in 41 age-matched healthy controls by multiplex polymerase chain reaction (PCR) using peripheral blood DNA samples. Result: While an association between the GSTM1 null genotype and PCa risk (OR= 3.69, 95% CI= 1.30-10.44; P = 0.01) was evident, the GSTT1 null genotype (OR= 0.92, 95% IC= 0.32-2.62; P = 0.49) appeared without influence. Furthermore, no statistically significant differences between the double null genotype and PCa is detected, also no statistically significant differences between smoking status and PCa is detected. Conclusion: The GSTM1 null genotype may increase individual susceptibility to prostate cancer. On the other hand, the null-activity genotype of GSTT1 did not appear to contribute to the risk of prostate cancer in our population.     

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 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.     

Cigarette smoking,glutathione-s-transferase M1 and t1 genetic polymorphisms,and breast cancer risk (United States)

Objective: It has been suggested that functional polymorphisms in genes encoding tobacco carcinogen-metabolizing enzymes may modify the relationship between tobacco smoking and breast cancer risk. We sought to determine if there is a gene–environment interaction between GSTM1 (GSTM1A and GSTM1B), and GSTT1 genotypes and cigarette smoking in the risk of breast cancer. Methods: Cases and controls were recruited in a case–control study conducted in Connecticut from 1994 to 1998. Cases were histologically confirmed, incident breast cancer patients, and controls were randomly selected from women histologically confirmed to be without breast cancer. A total of 338 cases and 345 controls were genotyped for GSTM1 and GSTT1. Results: None of the GSTM1 genotypes, either alone or in combination with cigarette smoking, was associated with breast cancer risk. There was, however, a significantly increased risk of breast cancer among postmenopausal women with a GSTT1 null genotype (OR = 1.9, 95% CI 1.2–2.9). There were also indications of increased risk of breast cancer associated with cigarette smoking for postmenopausal women with GSTT1-null genotype, especially for those who commenced smoking before age 18 (OR = 2.9, 95% CI 1.0–8.8). Conclusion: Women with a GSTT1-null genotype may have an increased breast cancer risk, especially postmenopausal women who started smoking at younger ages.     

Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and susceptibility to gastric cancer: a meta-analysis

The association between glutathione S-transferase T1 (GSTT1) polymorphism and gastric cancer risk has been both confirmed and refuted in a number of published studies. Most of these studies were based on small sample sizes. We carried out a meta-analysis of the research published up to August 2005 to obtain more precise estimates of gastric cancer risk associated with GSTT1 polymorphism. In the present study, 16 case-control studies (with a total of 6717 subjects) were eligible for meta-analysis. There was no evidence of heterogeneity between the studies. The GSTT1 null genotype conferred a 1.06-fold increased risk of gastric cancer, which was not significant (95% confidence interval [CI]: 0.94-1.19). However, in the analysis of ethnic groups, we observed distinct differences associated with GSTT1 status. Restricting analyses to ethnic groups, the pooled odd ratios for the GSTT1 genotype were 1.27 in Caucasians (95% CI: 1.03-1.57) and 0.98 in Asians (95% CI: 0.86-1.13). Glutathione S-transferase M1 (GSTM1) and GSTT1 are involved in detoxification of a variety of compounds, some that overlap between enzymes and some that are highly specific. To investigate whether the profile of glutathione S-transferase genotypes was associated with risk of gastric cancer, further analyses combining the GSTT1 and GSTM1 genotypes were also carried out. There was a significant trend in risk associated with zero, one and two putative high-risk genotypes (chi2 = 9.326, d.f. = 1, P = 0.0023). Those who had null genotypes of GSTM1 and GSTT1 had an increased gastric cancer risk compared with those who had both active genes (odds ratio = 2.08, 95% CI: 1.42-3.10).