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.     

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.     

Associations of CYP1A1, GSTM1 and GSTT1 Polymorphisms with Lung Cancer Susceptibility in a Northern Indian Population

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.     

Systematic Analysis on the GSTM1 Null Phenotype and Prostate Cancer Risk in Chinese People

Objective: Glutathione S-transferase M 1 (GSTM1) is implicated as a risk factor for prostate cancer.However, this issue is not clear in Chinese population. This systemic analysis was conducted to evaluate theeffect of GSTM1 null genotypes on prostate cancer risk in Chinese. Methods: Published studies investigating theassociations between GSTM1 null genotypes and the risk of prostate cancer in China were identified by using apredefined search strategy. Main statisticals were pooled and estimated according to the primarily reported data.Results: The prevalence of the GSTM1 null genotype was higher in prostate cancer patients than in controls,with significance. Conclusion: The GSTM1 null genotypes is associated with increased risk of prostate cancerin Chinese.     

Polymorphisms at GSTM1 and GSTP1 Gene Loci and Risk of Prostate Cancer in a South Indian Population

Inter-individual differences in cancer susceptibility may be mediated in part through polymorphic variability in ‍the bioactivation and detoxification of carcinogens. The glutathione S-transferases (GSTs), which are active in ‍detoxification of wide variety of carcinogens, have been consistently implicated as cancer susceptibility genes in this ‍context. We here assessed the association of GSTM1 and GSTP1 polymorphisms with susceptibility to prostate ‍cancer in a case-control study of 75 patients and 100 age-matched controls in a South Indian population. The ‍GSTM1 null polymorphism was detected by PCR and the GSTP1 Ile105Val polymorphism by PCR-RFLP using ‍peripheral blood DNA.There was no significant link between the null genotype of GSTM1 and risk of prostate ‍cancer (OR-1.79; 95% CI-0.78-4.11; P-0.18). However, the GSTP1 Ile/Val genotype was significantly associated with ‍a decreased risk for prostate cancer (OR-0.36; 95% CI-0.18-0.73; P<0.001). Analysis of the variant GSTM1 and ‍GSTP1 genotypes in combination did not reveal any significant difference between cases and controls, even with a ‍stratified analysis tumor grades. Thus our study indicates that the GSTP1 Ile/Val genotype may decrease risk of ‍prostate cancer in the South Indian population.     

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.     

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.     

CYP1A1, GSTM1, GSTT1 and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians

The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.     

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.     

IGlutathione S-transferase (GSTM1 and GSTT1) Polymorphisms in Cervical Cancer in Northeastern Thailand

To evaluate the relationships between genetic polymorphisms of the GSTs (GSTM1 and GSTT1) and cervicalcancer, the null genotype of each gene was studied in squamous cell cervical cancer (SCCA) patients (n=90) andcontrols (n=94) in Northeast Thailand. The prevalence of the GSTM1-null genotype in the controls and SCCApatients was 59.6% and 60.0%, respectively, whereas those of the GSTT1-null genotype in the control andSCCA patients was 40.4% and 46.7%, respectively. Neither of the GST-null genotypes increased the risk forSCCA (p>0.05); however, the combination of the GSTM-1 and GSTT1-null genotypes showed a non-significanttrend to an increased risk for developing cervical cancer with an adjusted OR of 2.7 (95%CI=0.8-9.0, p=0.10).Genetic polymorphisms of GSTM1 and GSTT1 were not significant risk factors for cervical cancer in eithertobacco-smokers or non-smokers. A different contribution of the GST genotype to cancer risk may be attributedto a different, as yet undefined, property of the enzymes.     

Genetic Polymorphism of GSTP1, GSTM1 and GSTT1 Genes and Susceptibility to Chronic Myeloid Leukaemia

Background: The development of cancer results from an imbalance between exposure to carcinogens and the capacity of various enzyme systems engaged in activation or in the detoxification of xenobiotics. The aim of the present study is to investigate the association of GSTP1, GSTM1 and GSTT1 gene polymorphisms in susceptibility to Chronic Myeloid Leukaemia (CML). Methods: A total of 200 CML patients and 100 controls were enrolled in a case-control study with GSTM1 and GSTT1 analysis with PCR and GSTP1 analysis with PCR-RFLP. Results: The GSTT1 null genotype was significantly higher among CML patients suggesting that this genotype is associated with an increased risk of CML. It was found in 42% of cases as compared with 21% of the controls, (OR =2.78, 95% CI: 1.59 - 4.85; p-value =0.000). The presence of the GSTT1 genotype may thus be considered a protective factor for CML. The frequency of individuals carrying GSTM1 null genotype was slightly higher in the control group but this difference was not statistically significant. The GSTM1 null genotype was present in 35% of control cases and 34% of the CML patients, (OR=0.975, 95%CI: 0.58-1.58;p-value=0.863). Individuals with a combined GSTM1 null/GSTT1null genotype had an estimated 2.85-fold increased risk of CML, but no associated risk between GSTP1 Ile 105 Val polymorphism and CML was found (OR=1.99, 95% CI: 0.40 - 9.32; p-value = 0.417). Conclusions: No association between GSTP1 and GSTM1 with susceptibility to CML was found. GSTT1 genotype may be a protective factor for CML, while the null genotype shows association with developing CML.     

Genetic Variation of GSTM1, GSTT1 and GSTP1 Genes in a South Indian Population

The glutathione S transferase (GST) family of enzymes play a vital role in the phase II biotransformation ofenvironmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic and the polymorphismsin GST genes have been associated with cancer susceptibility and prognosis. Moreover, distinct ethnic differenceshave been observed in the type and frequency of GST gene polymorphisms. Hence, the present study was aimed todetermine the frequencies of GSTM1, GSTT1 and GSTP1 polymorphisms in 255 healthy random volunteers fromSouth India. The GSTM1 and GSTT1 genotypes were determined by PCR and GSTP1 by PCR-RFLP using peripheralblood DNA.The GSTM1 and GSTT1 null genotype frequencies were found to be 22.4% and 17.6% respectively. TheGSTP1 allelic frequency was 0.78 for the Ile allele and 0.22 for the Val allele and the genotype frequency was 58.4%for Ile/Ile, 38.4% for Ile/Val, and 3.1% for Val/Val. Comparison of the frequencies of GST polymorphisms observedin the present study with other Indian and world populations revealed a distinctive nature of the South Indianpopulation with respect to polymorphims at the GST gene loci. A better understanding of carcinogen metabolizinggene distribution should contribute to risk assessment of humans exposed to environmental carcinogens.     

Methionine Synthase Reductase-A66G and -C524T Single Nucleotide Polymorphisms and Prostate Cancer: A Case-Control Trial

Purpose: Some variations in the sequence of methionine synthase reductase (MTRR) gene can increase the risk ofvarious cancers such as prostate cancer. The aim of this study was to investigate the association between prostate cancerand the MTRR A66G and C524T gene single nucleotide polymorphisms (SNPs) using an in silico analysis. Methods:In this case-control study, 218 Iranian men, including 108 men with prostate cancer and 110 prostate cancer-free men,were enrolled. The MTRR A66G and C524T genotyping was performed by PCR-RFLP. Some of the bioinformaticstools were employed for the evaluation of polymorphism on the molecular aspects of the MTRR. Results: With regardto the MTRR A66G polymorphism, the genotype AG (OR: 0.85, 95% CI: 0.47-1.54, p= 0.6014), genotype GG (OR:0.89, 95% CI: 0.42-1.87, p= 0.7512), and allele G (OR: 0.92, 95% CI: 0.63-1.35, p= 0.6686) were not associated withprostate cancer risk. However, the data for C524T SNP showed that the genotype CT was associated with prostatecancer risk (OR: 1.92, 95% CI: 1.06-3.47, p= 0.0308). Further, carriers of the allele T (OR: 1.80, 95% CI: 1.04-3.13,p= 0.0358) were associated with high risk of prostate cancer. In addition, bioinformatics analysis revealed that C524TSNP could affect some molecular aspects of the protein structure, while having no effect on the mRNA structure.Conclusion: The MTRR C524T is a genetic risk factor for prostate cancer; however, the MTRR A66G is not suggestedas a suitable biomarker for prostate cancer. To obtain more reliable results, further studies are recommended to uselarger sample sizes and investigate the effects of environmental factors.     

Genetic Deletions of GSTM1 and GSTT1 in Head and Neck Cancer: Review of the Literature from 2000 to 2012

Head and neck cancer is one of the leading causes of deaths worldwide. Two genes GSTM1 and GSTT1 involvedin phase II of carcinogen detoxification have been frequently studied in the literature. Their null genotypes arethought to be associated with increased head and neck cancer risk. However, the published reviews are not upto date and many important papers have been skipped. The current literature review was restricted to the nullgenotypes of the GSTM1 and GSTT1 genes with special emphasis on the genotypic status. We found that thesize of study sample varied greatly and the oral cavity cancer was more influenced by GSTM1 and GSTT1 genedeletions. With respect to ethnicity Asians are more prone to head and neck cancers with these null genotypes ascompared to Europeans and Americans. The current review showed significant associations (OR=9.0, 95%CI;1.4-9.5; OR=3.7, 95%CI; 1.4-9.5) of GSTM1 and GSTT1 null genotypes with head and neck cancers. Reviewconfirms the data of previous reviews that GSTM1 and GSTT1 gene polymorphisms may be risk factors forcancer initiation.     

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.     

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.     

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.     

Glutathione S-transferases (GSTT1 and GSTM1) gene deletions in Tunisians: susceptibility and prognostic implications in breast carcinoma

Glutathione S-transferase Theta1 and Mu1 (GSTT1 and GSTM1) are involved in the metabolism and detoxification of a wide range of potential environmental carcinogens. Conversely, they contribute to tumour cell survival by detoxification of numerous products induced by cancer therapy. The authors designed a large study to investigate the susceptibility and prognostic implications of the GSTT1 and GSTM1 gene deletions in breast carcinoma. The authors used the polymerase chain reaction to characterise the variation of the GSTT1 and GSTM1 genes in 309 unrelated Tunisian patients with breast carcinoma and 242 healthy control subjects. Associations of the clinic-pathologic parameters and the genetic markers with the rates of the breast carcinoma specific overall survival (OVS) and the disease-free survival (DFS) were assessed using univariate and multivariate analyses. A significant association was found between gene deletion of GSTT1 and the risk of early onset of breast carcinoma (OR=1.60, P=0.02). The lack of GSTT1 gene deletion was significantly associated with poor clinical response to chemotherapy (OR=2.29, P=0.03). This association was significantly higher in patients with axillary's lymph node-negative breast carcinoma (OR=12.60, P=0.005). The null-GSTT1 genotype showed a significant association with increased DFS in this selected population of patients. This association was even higher in patients carrying both null-GSTT1 and -GSTM1 genotypes. The gene deletion of GSTs may predict not only the early onset of breast carcinoma but also the clinical response to chemotherapy and the recurrence-free survival for patients with lymph node-negative breast carcinoma.     

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。