GSTT1 Research Articles

Is nullity for Glutathione S-transferase genes GSTT1 and GSTM1 protective against leprosy?

Introduction: Leprosy is a slow and progressive infectious disease caused by Mycobacterium leprae. The generation of free radicals called reactive oxygen species (ROS), which promote destruction of the bacillus within macrophages, is an effective defence mechanism developed by the host. In parallel, the glutathione S-transferase (GST) multifamily of enzymes constitutes an important antioxidant system for ROS detoxification and protection against toxicity. Therefore, GST null genotype individuals could reduce the detoxification of ROS, increasing host effectiveness for M. leprae destruction. Objectives: To evaluate polymorphisms in the GSTT1 and GSTM1 genes as human leprosy susceptibility modulators. Methods: GSTT1 and GSTM1 polymorphisms were genotyped by a multiplex polymerase chain reaction (PCR) in 218 leprosy patients and 244 non-leprosy subjects (control group). Results: The occurrence of the GSTT1/GSTM1 null genotype was significantly higher among control subjects than amongst leprosy patients (P = 0.01). The GSTT1 positive genotype frequency was significantly increased in leprosy patients when compared with control subjects (P = 0.01). Conclusions: The results suggest that GSTT1/M1 nullity may play an important role in leprosy pathogenesis. Significance: Despite these findings, further studies will be necessary to ascertain the exact role of these genes in leprosy and to design any future prevention measures or contributions to drug therapy.

Expression Levels of Some Detoxification Genes in Liver and Testis of Rats Exposed to a Single Dose of Methyl-Tertiary Butyl Ether.

AIM:Methyl-tertiary-butyl ether (MTBE), a well-known gasoline oxygenate compound, is still used in several countries. Several studies investigated the effects of MTBE on the activity of phase II metabolism enzymes. There is no published data on the effect(s) of short-term exposure to MTBE on mRNA levels of antioxidant genes. Therefore, the present study was carried out.METHODS:A total of 15 adults male Wistar rats were randomly divided into five equal experimental groups. They received a single dose of 0, 400, 800 and 1600 mg/Kg MTBE in peanut oil by gavages. The final group received no MTBE and peanut oil. After 24 hr animals were slaughtered then livers and testis were removed to extract the total RNA. Real-time PCR was done to detect the gene expressions of glutathione S-transferase family (Gstt1, Gstm1, and Gstp1).RESULTS:The mRNAs levels of the examined genes neither in liver nor in testis showed a significant difference between the exposed groups and control rats.CONCLUSIONS:The present data revealed that exposure to a single dose of MTBE has no significant effect on the mRNA levels of the Gstt1, Gstm1, and Gstp1 genes.

Association of GSTT1 and GSTM1 gene polymorphisms with coronary artery disease in North Indian Punjabi population: a case-control study

BackgroundGlutathione S-transferases are metabolic enzymes which are responsible for detoxification of endogenous (products of oxidative stress) as well as exogenous (drugs, pesticides, herbicides, environmental pollutants and carcinogens) products. Dysfunctional detoxification...

Environmental and personal determinants of the uptake of disinfection by-products during swimming

BackgroundTrihalomethanes (THMs) in exhaled breath and trichloroacetic acid (TCAA) in urine are internal dose biomarkers of exposure to disinfection by-products (DBPs) in swimming pools. ObjectiveWe assessed how these biomarkers reflect the levels of a battery of DBPs in pool water and trichloramine in air, and evaluated personal determinants. MethodsA total of 116 adults swam during 40min in a chlorinated indoor pool. We measured chloroform, bromodichloromethane, dibromochloromethane and bromoform in exhaled breath and TCAA in urine before and after swimming, trichloramine in air and several DBPs in water. Personal determinants included sex, age, body mass index (BMI), distance swum, energy expenditure, heart rate and 12 polymorphisms in GSTT1, GSTZ1 and CYP2E1 genes. ResultsMedian level of exhaled total THMs and creatinine adjusted urine TCAA increased from 0.5 to 14.4µg/m3 and from 2.5 to 5.8µmol/mol after swimming, respectively. The increase in exhaled brominated THMs was correlated with brominated THMs, haloacetic acids, haloacetonitriles, haloketones, chloramines, total organic carbon and total organic halogen in water and trichloramine in air. Such correlations were not detected for exhaled chloroform, total THMs or urine TCAA. Exhaled THM increased more in men, urine TCAA increased more in women, and both were affected by exercise intensity. Genetic variants were associated with differential increases in exposure biomarkers. ConclusionOur findings suggest that, although affected by sex, physical activity and polymorphisms in key metabolizing enzymes, brominated THMs in exhaled breath could be used as a non-invasive DBP exposure biomarker in swimming pools with bromide-containing source waters. This warrants confirmation with new studies.

GENE POLYMORPHISMS, MERCURY CONCENTRATION, AND CYTOGENETIC DAMAGE IN THE INHABITANTS OF THE MERCURY ORE MININING AND RECYCLING AREA

The aim of the study was to evaluate the association between the frequency of cytogenetically damaged lymphocytes, glutathione- S-transferase (GST) gene polymorphisms, and mercury concentrations in the peripheral blood of mercury industry workers as well as an non-exposed local population (control group) of Aktash village, the Republic of Altay. The venous blood samples were obtained from 184 workers and 156 controls for chromosome assay, mercury blood concentration analysis, and the GSTM1 and GSTT1 gene polymorphism assessment by a polymerase chain reaction approach. Statistical analyses were carried out using Student's t-test, one-way ANOVA, or linear multiple regression. We demonstrated a significant increase in the frequency of lymphocytes with aneuploidy and polyploidy in the workers as compared with the controls (p < 0.001). The highest levels of aneuploidal and polyploidal lymphocytes were determined in the subgroup of workers with double null GSTM1(0)/GSTT1(0) genotype (p

Genotypes of GSTM1 and GSTT1: Useful determinants for clinical outcome of bladder cancer in Pakistani population

BackgroundIncidence of bladder cancer has increased rapidly worldwide in the past few years. Environmental as well as genetic factors are involved in the etiology of bladder cancer. Glutathione S transferase mu 1 (GSTM1) and glutathione S transferase theta 1 (GSTT1) genes are two xenobiotic metabolizing genes in phase II of detoxification process. AimThe current study was aimed to find out the association of different environmental factors and GSTM1 and GSTT1 gene polymorphisms with susceptibility to bladder cancer in Pakistani population. MethodBladder cancer cases (236) and control blood samples (270) were screened using phenol chloroform method of DNA extraction followed by multiplex PCR. ResultsWith respect to age; bladder cancer was more prevalent in age >60years and low grade tumors were more frequent than high grade tumors. Smokers had a significantly higher incidence rate of cancer; also family history of cancer was found to be strongly associated (P<0.05) with bladder cancer. Commonly reported symptoms by the patients of bladder cancer were hematuria, lower urinary tract symptoms (LUTS) and flank pain. A larger number of patients had undergone surgery, chemotherapy and radiotherapy. Similarly GSTM1 (OR 2.24; CI 1.5–3.2; P=0.0001) and GSTT1 (OR 2.9; CI 1.4–6.1; P=0.002) gene deletion showed a highly significant association with bladder cancer. Simultaneous deletions of both GSTM1 and GSTT1 genes also showed highly significant association (OR 5.3; CI 2.1–13.1; P=0.0001) with cancer risk. No association was found when both of the two genes deletion was compared with bladder cancer among smokers. ConclusionThis study suggests that GSTM1 and GSTT1 gene polymorphisms may be associated with increased susceptibility toward bladder cancer in Pakistani population.

Disinfection by-products exposure and intra-uterine growth restriction: Do genetic polymorphisms of CYP2E1or deletion of GSTM1 or GSTT1 modify the association?

BackgroundExposure to disinfection by-products (DBPs) during pregnancy was associated with reduced foetal growth. Genetic susceptibility might play a role, especially for genes encoding for the Cytochrome P450 (CYP2E1) and Glutathione S-Transferase (GST) enzymes, involved in metabolism and activation of DBPs. Few epidemiological studies evaluated these gene-environment interactions and their results were never replicated. ObjectiveThis study aims to examine interactions between trihalomethanes (THM) or haloacetic acids (HAA) exposure and genetic polymorphisms on small for gestational age (SGA) neonates by investigating single nucleotide polymorphisms (SNPs) in CYP2E1 gene and GSTM1 and GSTT1 deletions in mothers-children pairs. MethodsA population-based case-control study of 1549 mothers and 1455 children was conducted on SGA and THM/HAA exposure. DNA was extracted from blood or saliva cells. Targeted SNPs and deletions were genotyped. Statistical interaction between SNPs/deletions and THMs or HAAs in utero exposure with regard to SGA occurrence was evaluated by unconditional logistic regression with control of potential confounders. ResultsPreviously reported positive modification of the effect of THM uterine exposure by mothers or newborns CYP2E1 rs3813867 C allele or GSTM1 deletion was not replicated. However interactions with CYP2E1 rs117618383 and rs2515641 were observed but were not statistically significant after correction for multiple testing. ConclusionsPrevious positive interactions between THMs exposure and CYP2E1 and GSTM1 were not replicated but interactions with other CYP2E1 polymorphisms are reported.

Do Variants in GSTs Modify the Association between Traffic Air Pollution and Asthma in Adolescence?

Polymorphisms in genes involved in the oxidative stress response may partially explain the documented heterogeneous associations between traffic-related air pollution (TRAP) exposure and asthma and allergies in children. We investigated whether the GSTT1, GSTM1 and GSTP1 gene polymorphisms modified the associations between TRAP exposure during the first year of life and asthma, wheeze and hay fever in adolescence. We used a birth cohort of 620 high risk infants from the Melbourne Atopy Cohort Study. TRAP exposure during the first year of life was defined as the cumulative length of major roads within 150 m of each participant’s residence during the first year of life. Wheeze, asthma and hay fever were measured at ages 12 (n = 370) and 18 (n = 434) years. The associations and interactions with glutathione S-transferases (GST s) were investigated using regression models. Overall, there was no relationship between TRAP exposure during the first year of life and current asthma, wheeze and hay fever at ages 12 or 18 years. However, in GSTT1 null carriers, every 100 m increase in cumulative lengths of major road exposure during the first year of life was associated with a 2.31-fold increased risk of wheeze and a 2.15-fold increased risk of asthma at 12 years. TRAP is associated with some respiratory outcomes in carriers of genetic polymorphisms in oxidative stress metabolism genes.

Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide.

ObjectiveTo investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST).MethodsWe carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline.ResultsMost patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02–24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064–10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed.ConclusionThis study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

ROLE OF POLYMORPHIC GENE VARIANTS SOD2, GSTT1, GSTM1 AND GSTP1 IN THE DEVELOPMENT OF BREAST CANCER OF WOMEN OF CHECHEN POPULATION

In the study, we investigated the role of polymorphic variants of genes of antioxidant protection SOD2 T / C (Ala16Val), GSTP1 A / G (Ile105Val), GSTM1 and GSTT1 Ins /Delin the development of malignancies (External testing) chest 564 women (208 women diagnosed with breast cancer (BC), 356 control group) of the Chechen population. For the studied populations have an increased frequency of polymorphisms Ala16Val, associated with the formation of malignant tumors, including breast External testing, but the differences are statistically insignificant character. The results showed no association between the presence of polymorphic variants SOD2 Ala16Val (T / C), GSTP1 (A / G), as well as deletions of genes GSTM1 and GSTT1 and the development of breast cancer in women of Chechen populations of cancer.

The state of bronchi remodeling in school-age children with bronchial asthma at the Glutathione-S-Transferase gene polymorphism

The aim of research was to establish connection between the bronchi remodeling processes and allelic polymorphism of GSTT1 and GSTM1 genes in school-age children with bronchial asthma (BA) for optimization of results of the basic treatment.Methods: 66 school children with bronchial asthma in the period without attacks underwent the complex examination. All patients underwent general clinic and spirographic examination, point assessment of the bronchial asthma controllability with the help of clinically-instrumental evaluation scale, the analysis of the sample of capillary blood by the method of multiplex polymerase chain reaction (PCR) for detecting the deletions in glutathione-s-transferase genes that is GSTT1 and GSTM1.Results: As the result of molecular and genetic analysis of studying of GSTT1 and GSTM1 genes polymorphism there were demonstrated that the (GSTT1+М1+) genotype homozygous on the normal copies was more often and took place in 40,9% of children, «null genotype» -in 9 patients (13,64 %), GSTT1-М1+ genotype was equally often, whereas the heterozygous GSTT1+М1- genotype was detected in every third patient (31,82 %).Conclusions: The deletion polymorphism of GSТT1 and GSТM1 in homozygous state (so called “null genotype” is three times less often in school children with bronchial asthma comparing with patients with GSTT1+М1+ genotype, it raises more than twice the risk of the heavy clinical course of disease, associates with the low indices of bronchi lability. In patients with bronchial asthma even at preserved structure of glutathione-s-transferase genes (GSTT1+М1+ genotype) the continuous contact with the tobacco smoke in family raises the content of endothelial factor of vessel growth (EFVG) in sputum in 1,25 times that underlines the more aggressive remodeling of respiratory tracts

Impact of null genotypes of GSTT1 and GSTM1 with uterine leiomyoma risk in Iranian population.

Few studies have investigated the role of the GSTM1 and GSTT1 genes in uterine leiomyoma. Therefore, in the current study the distribution of these genotypes in Iranian women and susceptibility to uterine leiomyoma was investigated. Blood samples of 50 patients with uterine leiomyoma and 50 healthy individual controls were collected in this cross-sectional study. Genomic DNA was extracted, and subsequently GSTM1 and GSTT1 null genotypes were detected by the Gap-polymerase chain reaction method. A total of 42% of patients appeared to lack GSTM1 enzyme activity due to the presence of an extended deletion (GSTM1 0/0 genotype), compared with 18% in a control group (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.35-9.37; P < 0.010). In addition, the prevalence of the GSTT1 null genotype in patients was higher than that in the control group (42% to 14%, P < 0.009). Also, it was shown that individuals with both null genotypes (-/-) had a 19.23-fold higher risk of developing the disease in comparison to people who showed both present genotypes (+/+). (P = 0.007; 95%CI, 2.20-167.41). Besides, it was observed that at least one null genotype increases the risk of myoma to 2.6 compared to the both present genotype (P-value < 0.03, 95%CI, 1.05-6.82). To our knowledge, this is first significant correlation between risk of uterine leiomyoma and null GSTM1 and GSTT1 genotypes among Iranian patients. Our data support the involvement of GSTM1 and GSTT1 in uterine leiomyoma liability, and especially its role as a genetic factor in the occurrence of this disease.

Genetic risk factors of cisplatin induced ototoxicity in adult patients.

Ototoxicity is an important adverse effect of using Cisplatin (cis-diamminedichloroplatinum) (CDDP) as aform of chemotherapy. The clinical picture of CDDP induced ototoxicity includes perceptive hearing impairment (reversible or permanent) and tinnitus. Ototoxicity manifests with considerable variability between patients. The objective of this prospective study was to investigate apossible genetic background to this variability. We assessed ototoxicity induced by therapeutic doses of CDDP in adult patients with germinative testicular tumors, or other tumors treated with an identical CDDP dosage scheme. Audiological examination before, during and after the treatment has shown deterioration in hearing; first in the high-frequencies and with increased CDDP cumulative doses, impairment in other frequencies as well. Occurrence of tinnitus was not dependent on the administered dose of CDDP, or the other risk factors examined in this study. The association of CDDP induced ototoxicity with genetic polymorphisms in candidate genes was examined. Our study has demonstrated an association of early onset of CDDP induced ototoxicity with the presence of two copies of GSTT1 gene (p=0,009) and withTallele of rs9332377 polymorphism in COMT gene (p=0,001).

Distribution of genetic variants of oxidative stress metabolism genes: Paraoxonase 1 (PON1) and Glutathione S-transferase (GSTM1/GSTT1) in a population from Southeastern Mexico

Background: Paraoxonase 1 (PON1) and glutathione S-transferases (GSTs) are involved in the biotransformation of xenobiotics. Variation in the enzyme concentration and activity suggests individual differences for the degree of protection against oxidative stress.Aim: This study analysed the distribution of SNPs Q192R, L55M (PON1) and variants in GSTM1 and GSTT1 genes in a population from Southeastern Mexico.Subjects and methods: One hundred and fifty-one Mexican Mestizo healthy volunteers were included. PON1 polymorphisms were determined by Taqman allele discrimination real time-PCR, whereas GSTM1 and GSTT1 genes were determined with a multiplex PCR-based method.Results: All genotypes were in Hardy-Weinberg equilibrium, except for GSTM1. The genotypic distributions of Q192R and L55M were 22% QQ, 48% QR, 30% RR, 62% LL, 34% LM and 4% MM, respectively, whereas the allele frequencies were 0.46 (Q), 0.54 (R), 0.79 (L) and 0.21 (M). The most frequent haplotype was R/L (46.7%). It was found that 31% and 9% of the individuals had the GSTM1 and GSTT1 null genotype, respectively. The frequency of the combined null genotype GSTM1*0/GSTT1*0 was 4.64%.Conclusion: The results showed that the frequencies of polymorphisms of PON1, GSTM1 and GSTT1 in the Yucatán population differ to those observed in other ethnic groups and provide useful data for epidemiological studies.

Analyses of Genetic Variations of Glutathione S-Transferase Mu1 and Theta1 Genes in Bangladeshi Tannery Workers and Healthy Controls.

Glutathione S-transferases (GSTs) belong to a group of multigene detoxification enzymes, which defend cells against oxidative stress. Tannery workers are at risk of oxidative damage that is usually detoxified by GSTs. This study investigated the genotypic frequencies of GST Mu1 (GSTM1) and GST Theta1 (GSTT1) in Bangladeshi tannery workers and healthy controls followed by their status of oxidative stress and total GST activity. Of the 188 individuals, 50.0% had both GSTM1 and GSTT1 (+/+), 12.2% had GSTM1 (+/−), 31.4% had GSTT1 (−/+) alleles, and 6.4% had null genotypes (−/−) with respect to both GSTM1 and GSTT1 alleles. Among 109 healthy controls, 54.1% were double positive, 9.2% had GSTM1 allele, 32.1% had GSTT1 allele, and 4.6% had null genotypes. Out of 79 tannery workers, 44.3% were +/+, 16.8% were +/−, 30.5% were −/+, and 8.4% were −/−. Though the polymorphic genotypes or allelic variants of GSTM1 and GSTT1 were distributed among the study subjects with different frequencies, the differences between the study groups were not statistically significant. GST activity did not vary significantly between the two groups and also among different genotypes while level of lipid peroxidation was significantly higher in tannery workers compared to controls irrespective of their GST genotypes.

Evaluation of deletion polymorphisms of glutathione S-transferase genes and colorectal cancer risk in ethnic Kashmiri population: A case-control study.

Glutathione S.transferases. (GSTs) are known to play a pivotal role in the detoxification of potential carcinogens, and their gene variation may alter susceptibility to colorectal cancer. (CRC). The aim of the study was to evaluate the genetic association of GSTM1 and GSTT1 gene deletion/null polymorphism with disease susceptibility and risk development in CRC patients of ethnic Kashmiri population. Genotype frequencies of GSTM1 and GSTT1 gene deletion/null polymorphism were compared between 160 CRC patients and 200 healthy controls using polymerase chain reaction multiplex. The frequency of GSTM1-null was found to be 76.2% in cases and 81.5% in controls and odds ratio. (OR) = 1.37 (95% confidence interval. [CI]: 0.82-2.28). Likewise, the GSTT1-null genotype was found in 75.5% of cases and 77.5% of controls and the OR = 1.14 (95% CI: 0.76-1.8). The overall association between the GSTM1-null and GSTT1-null polymorphism and the CRC cases was found to be insignificant (P < 0.05). However, individuals with double-null genotype (GSTM1-/GSTT1-) were found to have 3.5-fold increased risk for the development of CRC. Further, the risk genotype (null) of GSTT1 was found to be associated with tumor grade (P = 0.001) and GSTM1 (null) genotype was significantly associated with smoking status (P = 0.004), when compared to the (present) genotype in CRC cases. Our results suggest that GSTM1 and GSTT1 gene deletion/null gene polymorphisms are not a key modulators of the risk of developing CRC in Kashmiri population.

Contribution of the GSTP1 gene polymorphism to the development of osteosarcoma in a Chinese population

We conducted a case-control study to investigate the associations between GSTT1, GSTM1, and GSTP1 gene polymorphisms and development of osteosarcoma in a Chinese population. Between January 2013 and February 2015, 153 patients diagnosed with osteosarcoma and 252 control subjects were enrolled in the current study from the Orthopedic Hospital of the Second Hospital of Jilin University. The GSTM1, GSTT1, and GSTP1 gene polymorphisms were detected by polymerase chain reaction coupled with restriction fragment length polymorphism analysis. As determined by a multiple-logistic regression analysis, the Val/Val genotype of GSTP1 was associated with a significantly increased risk of osteosarcoma compared to that of the Ile/Ile genotype, with an odds ratio (OR) = 3.39, and a 95% confidence interval (CI) = 1.45-8.13. Moreover, the Ile/Val+Val/Val genotype of GSTP1 was correlated with a marginally significant increased risk of osteosarcoma compared to that of the Ile/Ile genotype (OR = 1.65, 95%CI = 1.08-2.53). However, we did not find any significant associations between the GSTM1 and GSTT1 gene polymorphisms and osteosarcoma risk. In conclusion, our results suggest that the GSTP1 gene polymorphism is associated with an increased risk of osteosarcoma, whereas the GSTM1 and GSTT1 gene polymorphisms may not influence the development of this cancer.

The synergy of tobacco and alcohol and glutathione S-transferase θ 1 gene deletion and oral squamous cell carcinoma.

Background:Oral squamous cell carcinoma (OSCC) is the leading cancer among males in India. It is related to tobacco habits and alcohol consumption as well as the individual susceptibility for xenobiotic metabolizing enzyme polymorphisms. Glutathione S-transferase θ 1 (GSTT1) is a Phase II metabolic enzyme which is directly involved in catalyzing chemicals to mutagenic intermediates. This gene is characterized by genetic polymorphism resulting in complete gene deletion and subsequent absence of the enzyme, which ultimately dictates the risk of cancer development. Scraping buccal mucosa to obtain DNA from the cells is a simple, readily acceptable and rapid method to detect and assess the gene.Aim:To assess GSTT1 gene deletion in individuals giving a history of tobacco smoking and/or chewing and alcohol consumption and absence of clinically detectable lesions; and in OSCC cases to gauge if GSTT1 gene deletion confers protection to an individual and whether it can be used as a “single” marker to arrive at this conclusion. To validate the use of buccal scrape for determining the genotype of an individual by assessing the polymorphism at GSTT1 gene locus (22q11.2).Materials and Methods:Fifty-two cases were evaluated using buccal mucosal scrapes of tobacco habituates for 8 or more years, without clinically evident lesion (Group I) and from mucosa of tobacco habituates with clinically evident and histopathologically confirmed OSCC (Group II). DNA extraction and genotype at GSTT1 gene locus was determined by polymerase chain reaction assay.Statistical Analysis:The results were statistically analyzed using Chi-square test.Results:90.66% of subjects had GSTT1 null genotype in Group I subjects. In Group II, subjects with both clinically and histopathologically diagnosed oral cancer, about 76.96% had GSTT1 null genotype.Conclusion:GSTT1 null genotype confers protection to individuals with tobacco habits and alcohol consumption, predominantly to those who used chewable form of tobacco and especially among female population. However, the influence of many other environmental, genetic and epigenetic factors should be considered for the genesis/occurrence of cancer.

Role of GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms in the response to chemotherapy and overall survival of advanced non-small cell lung cancer.

We evaluated the association between GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms and treatment outcomes of advanced non-small cell lung carcinoma. Between January 2010 and December 2012, a total of 244 patients with non-small cell lung carcinoma were recruited from Yiwu Central Hospital. The GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and the results were statistically analyzed. Conditional regression analysis, showed that individuals carrying the null GSTM1 were associated with an increased risk of response to chemotherapy when compared to the present GSTM1 (odds ratio = 1.88, 95% confidence interval (CI) = 1.01-3.47). Moreover, the GG genotype of GSTP1 IIe105Val was associated with a better response to chemotherapy compared to the AA genotype (odds ratio = 2.77, 95%CI = 1.14-6.64). The null GSTM1 genotype was associated with a lower risk of death from all causes when compared with the present GSTM1 genotype (hazard ratio = 2.16, 95%CI = 1.10-4.38). Moreover, the GG genotype of GSTP1 IIe105Val was correlated with a reduced risk of death from all causes compared with the AA genotype (hazard ratio = 2.94, 95%CI = 1.11-8.68). In conclusion, we found that the null GSTM1 and the GG genotype of GSTP1 IIe105Val were correlated with a good response to chemotherapy and improved overall survival of advanced non-small cell lung carcinoma patients.

Association of GSTM1 and GSTT1 deletion with lung cancer development in Pakistani population.

Lung cancer has increased rapidly in the past few decades. Environmental and genetic factors are contributing toward its incidence. Several studies have been reported with conflicting results regarding polymorphism of GSTM1 and GSTT1 genes and their contribution in development of lung cancer. It has been observed that these genetic polymorphisms show geographical variations. Therefore, we conducted a case control study to find the association of various environmental factors as well as GSTM1 and GSTT1 deletion with susceptibility of lung cancer. DNA of pathologically confirmed lung cancer patients and cancer-free controls were amplified using multiplex PCR to check the deletion of GSTM1 and GSTT1 genes. Demographic factors like age, gender, smoking, passive smoking, smoking duration, smoking dose and other addictions were found to be significantly related (P = 0.05) with incidence of lung cancer. Deletion of GSTM1 and GSTT1 showed non--significant results (P = 0.05) when comparing with development of lung cancer. Results revealed that certain environmental factors may be considered as a risk factor but deletion of GSTM1 and GSTT1 are not associated with the development of lung cancer; however, studies including >500 patient samples is suggested.