Frequency Of GSTM1 Research Articles

Investigation of glutathione S-transferase M1 and T1 deletions in lung cancer

Glutathione S-transferases (GSTs) M1 and T1 are known to be polymorphic in humans. Both polymorphisms are due to gene deletions which are responsible for the existence of null genotypes. Previous studies have suggested that GST genotypes may play a role in determining susceptibility to a number of unrelated cancers, including lung cancer. The GSTM1 and GSTT1 polymorphisms were determined by PCR-based analysis in 75 lung cancer patients and 55 controls. The unconditional logistic regression analysis was used to calculate ORs and 95% CI. The frequencies of GSTM1 and GSTT1 null genotypes were 37.3 and 22.7% in lung cancer patients and 27.3 and 16.4% in controls, respectively. When analyzed by histology the GSTM1 null genotype was more prevalent in squamous-cell carcinoma and adenocarcinoma patients. Whereas, GSTT1 null genotype frequency was lower in small-cell lung cancer patients than controls. But these differences were not statistically significant. According to smoking status, null genotype for both gene are associated with an increase in risk for lung cancer. Our results suggest that GSTM1 and GSTT1 polymorphisms may play a role in the development of lung cancer for some histological subtypes and modifies the risk of smoking-related lung cancer.

Studying the Association of Polymorphic Variants of GSTM1 and GSTT1 Genes with Breast Cancer in Female Residents of Altai Krai

The incidence of homozygote deletion of glutathione S-transferase genes M1 and T1 (null genotypes; or GSTM1"-" and GSTT1"-") was studied in breast cancer patients living in Altai Krai. DNA was isolated from blood samples of 695 breast cancer patients (291 patients with familial cancer and 404 patients with sporadic cancer) and 263 women without history of tumor diseases. The frequency of GSTM1"-" and GSTT1"-" genotypes was estimated in breast cancer patients (47.2 and 19.1%, respectively) and non-cancer participants (46.8 and 19.0%, respectively). No differences were found in the frequency of genotypes. The frequency of genotype combination GSTM1"-"+GSTT1"-" in patients with sporadic breast cancer (11.6%, 47 of 404 patients) was higher than in the control (6.1%, 16 of 263 patients; OR=2.03; 95% CI=2.09-3.83; p=0.02). The genotype frequency of genes in the control group did not differ from that in European residents of the Caucasian race.

Cytochrome P450 1A1, glutathione S-transferases M1 and T1 polymorphisms in Ovambos and Mongolians

Cytochrome P450 (CYP) 1A1, glutathione S-transferase (GST) M1, and GSTT1 gene polymorphisms have been shown to be associated with several diseases. In this study, CYP1A1 MspI, GSTM1 and GSTT1 gene polymorphisms were investigated in 134 Ovambo and 207 Mongolians, and the results were compared with those from previous studies. Using polymerase chain reaction/restriction fragment length polymorphism (PCR–RFLP) the frequency of CYP1A1 MspI mutation was determined. The multiplex PCR was used to determine the GSTM1 and GSTT1 polymorphism. The frequencies of wild-type, heterozygous variant and homozygous variant of the CYP1A1 MspI genotypes were 72.4%, 25.4% and 2.2%, and 22.7%, 55.6% and 21.7% in the Ovambos and Mongolians, respectively. The frequencies of GSTM1 (null) and GSTT1 (null) genotypes were 11.2% and 35.8%, and 46.4% and 25.6% in the Ovambos and Mongolians, respectively. The CYP1A1 MspI and GSTT1 (null) genotype distribution of the Ovambos was similar to that of African-Americans and some Caucasians. In contrast, the GSTM1 (null) genotype distribution was different from that of all other populations. Among Mongolians, the CYP1A1 MspI polymorphism showed the highest mutation frequencies, GSTM1 (null) was similar to that of East Asians, and GSTT1 (null) was different from that of almost all the Asians examined.

GSTM1, GSTT1, and GSTP1 Polymorphism in North Indian Population and its Influence on the Hydroquinone-Induced In Vitro Genotoxicity

Glutathione S transferase (GST) gene polymorphism examined among north Indians and correlated with hydroquinone (HQ) genotoxicity to help in clinical prediction of susceptibility of HQ toxicity. Lymphocytes of individuals with/without GSTM1, GSTT1, and GSTP1 (ile/ile or val/val) were exposed to HQ (20, 40, or 80 μM) and examined chromosomal aberrations (CA) or cytokinesis-block micronucleus assays. Among north Indians the frequencies of GSTM1 (null), GSTT1 (null), and both null were found to be 41.1, 21.9, and 12.7%, whereas frequencies of GSTP1 with (ile/ile) or (ile/val), or (val/val) were 52, 42.1, or 5.9%, respectively. Individuals with null GSTM1, GSTT1, and GSTP1 (val/val) showed inhibition of mitotic index (MI) and significant (p < 0.01) induction of CA as compared to individuals with GSTM1, GSTT1, and GSTP1 (ile/ile). Micronucleus formation was found to be significant (p < 0.05 or 0.01) in both the genotypes. Results indicate that GSTM1, GSTT1 (null), and GSTP1 (val/val) are sensitive to HQ genotoxicity.

Polymorphism of CYP1A1*2C, GSTM1*0, and GSTT1*0 in a Mexican Mestizo Population: A Similitude Analysis

Cytochrome 1A1 (CYP1A1), glutathione transferase M1 (GSTM1), and glutathione transferase T1 (GSTT1) catalyze the bioactivation and detoxification of a wide variety of xenobiotic compounds that are mutagenic and/or carcinogenic (e.g., polycyclic aromatic hydrocarbons). Genetic polymorphisms of these metabolizing enzymes have been shown to affect individual susceptibility to environmental carcinogenic compounds. Although several studies have been published on the relationship between CYP1A1*2C, GSTM1*0, or GSTT1*0 polymorphism and cancer, not all findings can be extrapolated to other populations because of interethnic variability. Here, we investigate the frequency of CYP1A1*2C, GSTM1*0, or GSTT1*0 in a sample of Mexican Mestizos. We find that the frequency of GSTM1*0 is 0.335, that of GSTT1*0 is 0.121, and that of GSTM1*0 + GSTT1*0 is 0.023. The frequency of CYP1A1*2C is 0.54. Similitude analysis sets the Latin American populations in a common cluster near the Asian population, suggesting that the CYP1A1*2C polymorphism may have originated from this population and suffered a founder effect in the American population. Analysis of CYP1A1*2C, GSTM1*0, and GSTT1*0 haplotypes reveals that 35% of the population has some combination of risk genotypes. Taken together, these results point to a high susceptibility of the Mexican Mestizo population to the effects of environmental carcinogens.

Polymorphism of CYP1A1*2C , GSTM1*0 , and GSTT1*0 in a Mexican Mestizo Population: A Similitude Analysis

Cytochrome 1A1 (CYP1A1), glutathione transferase M1 (GSTM1), and glutathione transferase T1 (GSTT1) catalyze the bioactivation and detoxification of a wide variety of xenobiotic compounds that are mutagenic and/or carcinogenic (e.g., polycyclic aromatic hydrocarbons). Genetic polymorphisms of these metabolizing enzymes have been shown to affect individual susceptibility to environmental carcinogenic compounds. Although several studies have been published on the relationship between CYP1A1*2C, GSTM1*0, or GSTT1*0 polymorphism and cancer, not all findings can be extrapolated to other populations because of interethnic variability. Here, we investigate the frequency of CYP1A1*2C, GSTM1*0, or GSTT1*0 in a sample of Mexican Mestizos. We find that the frequency of GSTM1*0 is 0.335, that of GSTT1*0 is 0.121, and that of GSTM1*0 + GSTT1*0 is 0.023. The frequency of CYP1A1*2C is 0.54. Similitude analysis sets the Latin American populations in a common cluster near the Asian population, suggesting that the CYP1A1*2C polymorphism may have originated from this population and suffered a founder effect in the American population. Analysis of CYP1A1*2C, GSTM1*0, and GSTT1*0 haplotypes reveals that 35% of the population has some combination of risk genotypes. Taken together, these results point to a high susceptibility of the Mexican Mestizo population to the effects of environmental carcinogens.

Null allele polymorphisms in the GSTT1 and GSTM1 genes in 705 women from a mammographic breast cancer screening program (NMPOA) in southern Brazil

21091 Background: Several genetic polymorphisms in genes related with metabolism have been associated with breast cancer (BC) risk. Among these, the gluthatione-S-transferase M1 and T1 null genotypes have been associated with slightly increased BC risk in some populations. In Brazil, BC is a significant public health problem, due to its high incidence and mortality rates. In Porto Alegre, Brazil`s southernmost capital, a multidisciplinary BC Prevention Project - the Nucleo Mama Porto Alegre Cohort (NMPOA)- was started in 2004 and includes a mammographic screening program for women ages 40–69 years. Goal:Determine the allelic and genotypic frequencies of GSTM1 and GSTT1 null alleles in women undergoing annual mammographic screening and correlate its presence with mammography results and presence of additional BC risk factors at baseline and after 10 years. Methods: A sample of 705 women from the NMPOA BC screening program was consecutively enrolled from November/2005 until March/2006. Mammography results (BIRADS categories) and BC risk information (5-yr and vital estimates using the Gail model, family history of BC, body mass index) were obtained by chart review. Genotyping was performed by multiplex polymerase chain reaction (PCR). Results: Of the 705 patients studied, 145 (20.6%) and 314 (44.5%) had the GSTT1 and GSTM1 null alleles, respectively. Genotypically, 67 (9,5%) were null homozygous for both genes (GSTM1- and GSTT1- ); 78 (11,1%) were GSTT1- and non-null for GSTM1 (GSTT1- and GSTM1+); 247 (35%) were GSTT1+ and GSTM1- and 313(44,4%) were GSTM+ and GSTT+. There was a statistically significant association of the GSTT1+ allele with low-risk mammographic findings (category BIRADS 1; p&lt;0,05). Conclusions: The genotypic and allelic frequencies of the GSTT1 and GSTM1 null alleles were not significantly different from those reported previously for other populations. The non-null GSTT1 allele was associated with lower category mammographic findings. Prospective clinical evaluation of the women followed in this program and correlation of genotype with clinical findings may elucidate additional risks associated with the presence of these polymorphisms. No significant financial relationships to disclose.

Are glutathione S-transferase gene polymorphisms linked to neonatal jaundice?

Glutathione S-transferases (GSTs) are a major group of phase II detoxification enzymes involved in the metabolism of both endogenous and xenobiotic compounds. In addition to their catalytic function in detoxification, GSTs participate in binding to nonsubstrate ligands such as bilirubin. Ligandin, which is one of the principal hepatic-binding proteins, is also a member of the GST family. The aim of the present study was to investigate the possible relationship between neonatal jaundice and the GST gene polymorphisms. The study cohort consisted of a patient group of 116 newborns (plasma bilirubin levels > or = 15 mg/dl) and a control group of 54 newborns (plasma bilirubin levels <13 mg/dl). In the patient group, the null genotype frequencies in GSTM1 and GSTT1 were 52.6 and 19%, respectively; in the control group, these were 63 and 27.8%, respectively. The frequencies of GSTM1 and GSTT1 were similar in the patient and control groups (p > 0.05). Total bilirubin levels were found to be significantly higher in patients with the GSTM1 null genotype than in patients with the GSTM1 wild genotype (p = 0.042). There was no statistically significant difference in total bilirubin levels between patients with the null GSTT1 genotype and those with the wild GSTT1 genotype. It is conceivable that there is a relation between GSTM1 gene polymorphism and total bilirubin levels in neonatal jaundice. We suggest that GSTM1 gene polymorphisms may affect ligandin functions in hepatocytes, which are important in bilirubin transportation. Consequently, patients with the GSTM1 null genotype may have higher total levels of bilirubin.

The role of GSTM1 gene polymorphisms in lung cancer development in Turkish population

BackgroundGlutathione S-transferase (GSTs) plays an important role in the detoxification of many xenobiotics involved in the etiology of cancer. In different ethnic groups, variations in null allele frequency have been observed. We have investigated GSTM1 gene polymorphisms in healthy subjects and lung cancer patients in the Turkish population and reviewed the control subjects of the studies performed in the Turkish population.MethodsFollowing blood sampling from patients and controls, DNA samples were extracted from the whole blood and were amplified by using polymerase chain reaction (PCR) method in all of the 256 cases, consisting of 102 previously diagnosed with lung cancer and 154 healthy controls.ResultsThe prevalence of GSTM1-null genotype in the lung cancer patients was 49%, compared to 52.6% in the control group (OR = 1.39, 95% CI = 0.70–1.90, p = 0.57). There were also no significant relationships in GSTM1 genotypes among histopathologic types of lung cancers (p > 0.05). The frequency of GSTM1 was found to be 41.2% (n = 1809) when the control subjects of the studies performed in Turkish population were reviewed.ConclusionWe have observed that GSTM1 genotype is not an independent risk factor for lung cancer.

Allele and genotype frequencies of metabolic genes in Native Americans from Argentina and Paraguay

Interethnic differences in the allele frequencies of CYP2D6, NAT2, GSTM1 and GSTT1 deletions have been documented for Caucasians, Asians, and Africans population. On the other hand, data on Amerindians are scanty and limited to a few populations from southern areas of South America. In this report we analyze the frequencies of 11 allele variants of CYP2D6 and 4 allele variants of NAT2 genes, and the frequency of GSTM1 and GSTT1 homozygous deleted genotypes in a sample of 90 donors representing 8 Native American populations from Argentina and Paraguay, identified as Amerindians on the basis of their geographic location, genealogical data, mitochondrial- and Y-chromosome DNA markers. For CYP2D6, 88.6% of the total allele frequency corresponded to *1, *2, *4 and *10 variants. Average frequencies for NAT2 *4, *5, *6 and *7 alleles were 51.2%, 25%, 6.1%, and 20.1%, respectively. GSTM1 deletion ranged from 20% to 66%, while GSTT1 deletion was present in four populations in less than 50%. We assume that CYP2D6 *2, *4, *10, *14; NAT2 *5, *7 alleles and GSTM1 and GSTT1 *0/*0 genotypes are founder variants brought to America by the first Asian settlers.

Glutathione S-Transferase Gene Polymorphisms in Italian Patients With Sudden Sensorineural Hearing Loss

To investigate the association between glutathione S-transferase (GST) gene polymorphisms and sudden sensorineural hearing loss (SSNHL) in a population of consecutive Italian patients. Assuming that reactive oxygen species formation may play a role in inner ear damage, we investigated whether profiles of GSTs antioxidant enzymes M1 and T1 genotypes may be associated with the risk of SSNHL. A prospective study in patients with SSNHL. We investigated 80 Italian patients with SSNHL for the frequency of GSTT1 and GSTM1 polymorphisms. Genotype distribution of all factors found in patients were compared with those of 80 healthy control subjects of the same ethnic background using chi and odds-ratio analysis. Statistical significance was accepted at a level of p < 0.05. In our series, the frequencies of GSTM1 and GSTT1 null genotypes did not differ from those of the control subjects. The few studies regarding genetic polymorphisms of GSTs in SSNHL are not conclusive. Further studies are needed to investigate the role of antioxidants including GSTs in SSNHL and to provide the lacking information to improve our knowledge in the field before implementing the use of genetic polymorphism in the SSNHL medicine daily practice.

Avaliação da influência da nulidade dos genótipos GSTT1 e GSTM1 na carcinogênese em cabeça e pescoço

To evaluate the influence of GSTM1 and GSTT1 null genotypes in head and neck carcinogenesis. The frequencies of GSTM1 and GSTT1 null genotypes were evaluated by multiplex polymerase chain reaction (PCR) in 45 patients with head and neck squamous cell carcinoma and in 45 control group individuals. Both groups were composed of smokers paired by gender, age and race. The GSTT1 null genotype was found in 24.4% of the patients and 17.7% of the control group (P= 0.606), while 44.4% of the patients and 48.8% of the control group were bearers of the GSTM1 null genotype (P=0.832). No associations between GSTT1 and GSTMI null genotypes and primary tumor sites were found. In our study, it was impossible to establish the influence of the GSTT1 and GSTM1 null genotypes in head and neck carcinogenesis.

The role of glutathione transferases M1 and T1 in individual susceptibility to bladder cancer in a Tunisian population

Background: Susceptibility to bladder cancer is thought to depend on interplay between genetic factors and environmental chemical carcinogens.Aim: This study seeks to determine the role of the glutathione transferases M1 and T1 null genotypes (GSTM1*0 and GSTT1*0) in individual susceptibility to bladder cancer in a Tunisian population.Method: Sixty-two patients with transitional cell carcinoma of the bladder cancer and 79 controls were examined with respect to the frequency of GSTM1 and GSTT1 null genotypes.Results: The frequencies of the GSTT1 null in the total group of bladder cancer cases vs. controls did not differ statistically. The proportion of GSTM1 null genotype in patients was 63% compared to 45% in controls group (OR = 2.03; 95% CI 0.97–4.24; p = 0.04). A significantly higher incidence of GSTM1 deletion genotype was found in smokers with bladder cancer compared to the controls (65.38% vs. 45.5%). Smokers lacking the GSTM1 gene are at an approximately 2.2-fold higher risk of bladder cancer (OR = 2.23, 95% CI 1–5.15; p = 0.03).Conclusion: This study suggests that in Tunisian subjects the GSTM1 null genotype may be associated with an increased risk of bladder cancer. This association appears to depend upon smoking status.

Glutathione S-transferase M1 and T1 genetic polymorphisms are not related to the risk of hepatocellular carcinoma: A study in the Spanish population

Glutathione S-transferases constitute a superfamily of enzymes that catalyse the inactivating conjugation of endogenous and environmental substrates involved in the pathogenesis of hepatocellular carcinoma (HCC) and glutathione. Genes encoding either glutathione S-transferase Mu-1 or Theta-1 ( GSTM1 and GSTT1, respectively) isoforms are polymorphic. Homozygotes for the mutated inactive alleles of each gene are devoid of any specific enzymatic activity (null genotypes). Our aim was to investigate whether individuals with null GST genotypes have a higher risk of developing HCC. A total of 184 Caucasian Spanish patients with a diagnosis of HCC and 329 healthy controls of the same ethnic origin were included. Polymorphisms in GSTM1 and GSTT1 genes were identified through multiplex polymerase chain reactions, and the dihydrofolate reductase ( DHFR) gene was used as internal control. No differences were found between the frequencies of GSTM1 (47.8% versus 45.3%) and GSTT1 (28.8% versus 23.1%) null genotypes in cases and controls, respectively, nor in the proportion of carriers of two, one or no active genotypes. Gender, age at diagnosis, tobacco use, chronic infection with hepatitis B or C virus and alcohol abuse did not influence these results. In conclusion, polymorphisms in GSTM1 and GSTT1 genes are not related to the incidence of HCC in a high-risk Spanish population.

Evaluation of the association between null genotypes of glutathione-S-transferases and Behcet’s disease

Glutathione S-transferases (GST) play an important role in oxidative stress related syndromes. An imbalance of the oxidant and antioxidant systems is important in the pathogenesis of Behcet's disease (BD). The objective of this study was to evaluate the association of null genotypes of GST-M1 and GST-T1 with BD since some preliminary molecular genetic data were recently published. Ninety-four Turkish BD patients (42 male, 52 female, 37.1+/-10.4 years) and 140 healthy volunteers (70 male, 70 female, 36.8+/-11.7 years) matched for age and gender with the patients as the control group were included in the study. Distributions of GST-M1 and GST-T1 genotypes were determined by multiplexed PCR using three sets of primers for GST-M1, GST-T1, and beta-globulin genes. There was no association between BD and the frequencies of GST-M1 and GST-T1 null genotypes when compared to controls by separate analysis. However, by cross and pooled combination analysis there was a significant association between the frequencies of pooled GSTs with one or both null genotypes in BD and controls. This is the first evidence that the association between the frequencies of GST-M1 and GST-T1 null genotypes and BD might be dependent on the interaction of multiple null allele polymorphisms rather than a single null allele of GST-M1 and GST-T1.

GSTM1, GSTT1 and GSTP1 polymorphisms in the Korean population.

The isoenzymes of the glutathione s transferase (GST) family play a vital role in phase II of biotransformation of many substances. Using a multiplex polymerase chain reaction and a direct sequencing analysis, the frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms were evaluated in 1,051 Korean male subjects. We found that 53.8% of the individuals had the GSTM1 null genotype and 54.3% had the GSTT 1 null genotype. The genotypic distribution of GSTP1 was Ile105/Ile105 in 68.4%, Ile105/Val105 in 29.1% and Val105/Val105 in 2.5%. The most frequently observed combination of GSTM1, GSTP1 and GSTT1 genotypes was Null type/Ile105/Ile105/Null type, while the combination of Non-null type/Val105/Val105/Non-Null type was not observed. We found that the genotype distributions of three GST isoenzymes in the Koreans are similar to those reported in Asians and previously reported Koreans. We believe our results, which are represented by a large population, are reliable estimates of the frequencies of the polymorphic GST alleles in the Koreans and will help future researches on GST polymorphisms.

Glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) polymorphisms and urothelial cancer risk with tobacco smoking

The objective of this study was to examine the association between the genetic polymorphism of glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) genes and urothelial cancer risk in relation to smoking status. In this study, 325 Japanese patients with urothelial transitional cell carcinoma and 325 healthy controls were compared for frequencies of GSTM1, T1 and NAT2 genotypes. The frequencies of GSTM1 null genotype and NAT2 slow genotype were significantly higher in the cases than in the controls (adjusted odds ratio (OR) 1.37, 95% confidence interval (CI) 1.01-1.87, adjusted OR 3.09, 95% CI 1.69-5.63, individually). Furthermore, the risk of GSTM1 null genotype and NAT2 slow genotype was higher among smokers (adjusted OR 1.48, 95% CI 1.01-2.15, adjusted OR 4.28, 95% CI 1.96-9.36, individually). The regression analysis of cancer risk as a function of the amount of smoking showed that the susceptibility of people who had GSTM1 null genotype increased from 45 pack-years, while the susceptibility of people with NAT2 intermediate or slow genotype increased rapidly from 25 pack-years, compared with non-smokers. A multiplicative interaction between NAT2 intermediate or slow genotype and pack-years of smoking was found (P<0.001), but GSTM1 null genotype was not (P=0.06). Our results indicate that the GSTM1 null genotype and NAT2 intermediate or slow genotype are associated with an increased risk of urothelial cancer in relation to smoking amounts. Furthermore, the interaction between NAT2 intermediate or slow genotype and pack-years of smoking has a strong impact on urothelial cancer.

Genetic polymorphisms analysis of glutathione S-transferase M1 and T1 in children with acute lymphoblastic leukemia.

The relationship between glutathione S-transferases (GSTs) M1, T1 genotype and childhood acute lymphoblastic leukemia (ALL) was investigated. GSTM1 and GSTT1 genotypes in genomic DNA from 67 children with ALL and 146 healthy controls were analyzed by using the multiplex polymerase chain reaction (PCR). The frequencies of GSTM1, M1-T1 null genotypes in ALL children were significantly higher than in the healthy controls (76.12% versus 52.74%, OR=2.856, P<0.001; 50.74% versus 24.66%, OR=3.148, P<0.001, respectively). However, there was no significant relationship between GSTT1 null genotype and ALL of children (61.19% versus 49.32%, OR=1.621, P>0.05). It was suggested that GSTM1 null genotype might be a risk genotype of childhood ALL, while there as no correlation between GSTT1 null genotype and childhood ALL.

CYP1A1, GSTM1 and GSTT1 genetic polymorphism is associated with susceptibility to polycystic ovaries in South Indian women

Polymorphic variants in the phase I enzyme, cytochrome P450 gene, may lead to increased toxification, whereas polymorphisms in the phase II enzyme, glutathione S-transferase genes, may result in impaired detoxification. Alterations in the activities of phase I drug metabolizing enzymes and phase II detoxification enzymes may cause abnormal functioning and formation of follicular cysts in the ovaries and thus causing an imbalance in the hormone profiles. This study aimed to investigate the relationship between genetic polymorphisms of CYP1A1 (T6235C), GSTM1 and GSTT1 in South Indian women with polycystic ovaries (PCO) using polymerase chain reaction–restriction fragment length polymorphism. The frequencies of variants of these genes were studied in 180 women with confirmed PCO and in 72 healthy fertile women with successful pregnancy record. No significant difference was found between the frequencies of GSTM1 and GSTT1 null genotypes in PCO cases and healthy controls. However, CYP1A1 Msp I homozygous mutants were strongly associated ( P = 0.0139) with increased susceptibility to PCO. Three genotype combinations, CYP1A1(mt/mt) with GSTM1[–] and GSTT1[–], CYP1A1(wt/mt) with GSTM1[–] and GSTT1[–] and CYP1A1(mt/mt) with GSTM1[–], GSTT1[+], were also observed in women with PCO. In conclusion, the presence of hyperinducible CYP1A1 (T6235C) mutant genotype and its mutants in combination with GSTM1 and GSTT1 null genotypes might cause an imbalance between phase I and phase II enzymes, and therefore may represent a risk factor for PCO.

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