Meta-analysis: glutathione S-transferase T1 null allele is associated with gastric cancer risk

Allelic variant within genes encoding glutathione S-transferase T1 (GSTT1) has been suggested to be a possible risk factor of gastric cancer, but previous studies provide controversial results. This study aimed to assess the effects of GSTT1 polymorphism on gastric cancer by means of meta-analysis. We included published studies on the relationship between GSTT1 null allele and gastric cancer risk after searching electronic databases. A meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95 % confidence intervals (95 % CI). Forty-two studies with a total of 8,203 gastric cancer cases and 13,866 controls were included into this meta-analysis. When all 42 studies were pooled into this meta-analysis, there was a significant association between the GSTT1 null allele and gastric cancer risk (OR?=?1.24, 95 % CI 1.14–1.36, P?<?0.00001). Sensitivity analysis by excluding individual studies showed that there was no effect on the pooled OR with 95 % CI. After excluding studies with low quality, there was still a significant association between the GSTT1 null allele and gastric cancer risk (OR?=?1.24, 95 % CI 1.13–1.36, P?<?0.00001). In the subgroup analysis, there was a significant association between the GSTT1 null allele and gastric cancer risk in both Europeans and Asians. There was no risk of publication bias in this meta-analysis. Our results suggest that GSTT1 null allele is associated with increased risk of gastric cancer.     

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.     

Quantitative assessment of the influence of glutathione S-transferase T1 null variant on gastric cancer risk

Glutathione S-transferase T1 (GSTT1) catalyzes reactions between glutathione and lipophilic compounds with electrophilic centers, leading to neutralization of toxic compounds, xenobiotics, and products of oxidative stress. In the past decade, a number of case–control studies have been carried out to investigate the relationship between the GSTT1 null polymorphism and gastric cancer (GC), but the results have been inconclusive. To investigate this inconsistency, we performed a meta-analysis of 46 studies involving a total of 9012 GC cases and 14,215 controls for null variant of the GSTT1 gene to evaluate the effect of GSTT1 on genetic susceptibility for GC. Potential sources of heterogeneity including ethnicity, source of control, and sample size were also assessed. Overall, significantly increased GC risk was associated with GSTT1 null polymorphism with OR of 1.20 (95 % CI, 1.10–1.32; P?<?0.05). In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians and Indians, while no significant associations were found among Caucasian, and Middle Eastern and African populations. By pooling data from 19 studies that considered combinations of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for GC (OR?=?2.04, 95 % CI, 1.49–2.64; P?<?0.05) was detected for individuals with dual deletion in both genes compared with positive genotypes. In addition, we found that cigarette smoking and alcohol drinking may modified the association of GSTT1 null genotypes with the risk of GC. In conclusion, this meta-analysis suggests that GSTT1 null polymorphism is associated with elevated GC risk, but these associations vary in different ethnic populations.     

Interaction of glutathione S-transferase M1 and T1 genotypes and malignant melanoma.

The mu and theta classes of glutathione S-transferases (GST) may affect the development of cutaneous malignant melanoma (CMM) by decreasing cellular oxidative stress in skin. These isozymes are absent in a large proportion of the population because of germ-line homozygous deletions in the genes encoding GSTM1 and GSTT1. To determine the association between GSTM1 and GSTT1 homozygous deletions (GSTM1 null and GSTT1 null, respectively) and CMM, we studied 212 patients with CMM, 150 patients with CMM and dysplastic nevi (DN), 147 patients with DN alone, and 124 healthy persons without CMM or DN. Comparing CMM cases (n = 362) to participants without CMM (n = 271), we found no association with GSTM1 null [odds ratio (OR), 1.2; 95% confidence interval (CI), 0.86-1.6] or GSTT1 null (OR, 0.82; 95% CI, 0.56-1.2), either independently or in combination (OR, 1.4; 95% CI, 0.81-2.2), after adjusting for age. However, among the subset of participants with red or blond hair, those with CMM were twice as likely to carry GSTM1 null (OR, 2.2; 95% CI, 1.2-4.2) and nearly 10-fold more likely to carry both GSTM1 null and GSTT1 null (OR, 9.5; 95% CI, 1.2-73) compared with those without CMM. These data suggest that among persons with hair colors traditionally associated with increased risk for melanoma, absence of both GSTM1 and GSTT1 may act to further elevate CMM risk.     

A population-based study of glutathione S-transferase M1, T1 and P1 genotypes and risk for lung cancer

A deletion polymorphism for glutathione S-transferase M1 (GSTM1) has been related to risk for lung cancer among smokers in some studies but not in others. We examined GSTM1, a GSTT1 deletion polymorphism and a common GSTP1 gene variant (iso→val), as risk factors for lung cancer in a population-based case-control study of men. Cases (N=274) were males identified from 1993 to 1996 through the Fred Hutchinson Cancer Research Center Cancer Surveillance System registry for western Washington State. Male age-matched controls (N=501) were selected by random-digit dialing. Subjects participated in a telephone interview and blood draw. GSTM1 and GSTT1 were genotyped with a multiplex PCR assay using beta-globin as a positive control, and GSTP1 single nucleotide variant determined with PCR-based oligonucleotide ligation assays. GSTM1 absence was associated with a modest elevation in risk among all cases (odds RATIO=1.27, 95% CI 0.91–1.77) and among non-small cell cancers (adenocarcinoma OR=1.58, 95% CI 0.99–2.52; squamous cell OR=1.40, 95% CI 0.83–2.34). Risk associated with GSTM1 null was increased two to sixfold among heavy smokers. GSTT1 was not associated with lung cancer risk and GSTP1 val was non-significantly associated with a modest reduction in risk, particularly among heavy smokers. No specific combination of GST genotypes was particularly associated with risk. These results support previous reports that the GSTM1 null genotype is associated with a modest increase in risk for lung cancer, particularly among heavy smokers, suggest no role for GSTT1 and the need for further study of GSTP1.     

Distribution of glutathione S-transferase M1, P1 and T1 genotypes in different age-groups of Finns without diagnosed cancer

BACKGROUND: Xenobiotic metabolizing enzymes (XMEs) are important detoxifiers of hazardous environmental agents, and their polymorphisms may therefore modify the risk of environmentally induced cancers. Consequently, the XME polymorphisms have been extensively studied in this context during recent years. Particular attention has been given to the polymorphisms of glutathione S-transferase (GST) M1, P1 and T1 genes. Previous studies have provided abundant data indicating these polymorphisms as important modifiers of individual susceptibility to cancers of environmental origin. It can be postulated that if the at-risk genotypes of these genes were real risk factors for the environmental cancers, their prevalence would presumably decrease with age in cancer-free part of the population. METHODS: We tested the hypothesis in a population based group of 2105 Finns (1,051 men, 1,054 women) in five age strata (27, 37, 47, 57 and 67 years of age), all without clinically diagnosed cancer. RESULTS: For GSTM1 genotype, a significant interaction was seen between gender and age among never smokers (p=0.003). Currently smoking men tended to be less likely (OR 0.57, 95% CI 0.31-1.03), and currently smoking women more likely (OR 1.70, 95% CI 0.97-2.97) homozygotes for the GSTP1*B allele compared with never smokers. Moreover, the likelihood of being a concurrent carrier of the putatively protective genotypes of all of the three studied GSTs was almost three-fold (OR 2.80, 95% CI 1.10-7.12) in heavy smokers in the two oldest age-groups compared with the other genotypes. CONCLUSIONS: Our findings based on a novel study design provide support to the previous case-control studies suggesting that GST genotypes modify individual risk of environmentally-induced cancers.     

Association between glutathione S-transferase M 1 null genotype and risk of ovarian cancer: a meta-analysis

Though previous studies investigated the association between glutathione S-transferase M 1 (GSTM1) null genotype and ovarian cancer risk, the effect of GSTM1 null genotype on ovarian cancer risk was still unclear. To comprehensively quantify the association between GSTM1 null genotype and ovarian cancer risk, we performed a meta-analysis. Eleven studies from ten publications were identified from PubMed database. The pooled odds ratio (OR) with its 95 % confidence interval (CI) was used to assess the association. Meta-analysis of the total 11 studies showed that GSTM1 null genotype was not associated with ovarian cancer risk (OR?=?1.03, 95 % CI 0.92–1.14, P?=?0.625). The cumulative meta-analyses showed a trend of no association between GSTM1 null genotype and ovarian cancer risk as information accumulated by year. There was no evidence of publication bias in the meta-analysis. Meta-analysis of the 11 available studies shows that GSTM1 null genotype is not associated with ovarian cancer risk.     

Association between glutathione S-transferase M1 null genotype and risk of gallbladder cancer: a meta-analysis

Glutathione S-transferases (GSTs) are a family of enzymes which are involved in the detoxification of potential carcinogens. Glutathione S-transferase M1 (GSTM1) null genotype can impair the enzyme activity of GSTs and is suspected to increase the susceptibility to gallbladder cancer. Previous studies investigating the association between GSTM1 null genotype and risk of gallbladder cancer reported inconsistent findings. To quantify the association between GSTM1 null genotype and risk of gallbladder cancer, we performed a meta-analysis of published studies. We searched PubMed, Embase, and Wanfang databases for all possible studies. We estimated the pooled odds ratio (OR) with its 95 % confidence interval (95 % CI) to assess the association. Meta-analysis of total included studies showed that GSTM1 null genotype was not associated with gallbladder cancer risk (OR?=?1.13, 95 % CI 0.88–1.46, P?=?0.332). Subgroup analysis by ethnicity showed that there was no association between GSTM1 null genotype and risk of gallbladder cancer in both Caucasians and Asians. However, meta-analysis of studies with adjusted estimations showed that GSTM1 null genotype was associated with increased risk of gallbladder cancer (OR?=?1.46, 95 % CI 1.02–2.09, P?=?0.038). Thus, this meta-analysis shows that GSTM1 null genotype is likely to be associated with risk of gallbladder cancer. More studies with well design and large sample size are needed to further validate the association between GSTM1 null genotype and gallbladder cancer.     

Cytochrome P4501A1 and glutathione S-transferase M1 genotypes as risk factors for prostate cancer in Japan

BACKGROUND: The p53 mutation spectrum of prostate cancers developing in Japan indicates a role for environmental factors. This suggests there might be differences in susceptibility due to genetic polymorphisms in metabolic activation enzyme genes. We analyzed genetic polymorphisms of the xenobiotic-metabolizing enzymes, CYP1A1 and GSTM1. METHOD: Genotyping of CYP1A1 and GSTM1 was investigated by using allele-specific PCR in 115 prostate cancer (PCa) patients and 204 control patients. RESULTS: The CYP1A1 Val/Val genotype significantly increased the risk for PCa (OR = 2.6; 95% CI = 1.11-6.25) and the Ile/Val genotype showed a similar tendency (OR = 1.4; CI = 0.86-2.29). Individuals with the GSTM1 (0/0) genotype demonstrated a slightly increased risk (OR = 1.3; CI = 0.82-2.04). The combination of the CYP1A1 Val allele and GSTM1 (0/0) genotype was associated with a higher risk (OR = 2.3; CI = 1.18-4.48) than the CYP1A1 Val allele alone. When cases were analyzed by age at initial diagnosis, the relative risks with both the CYP1A1 Val allele and the GSTM1 (0/0) genotype were higher in the young group than in the old group (CYP1A1; OR = 1.7, CI = 0.89-3.17: GSTM1; OR = 1.6, CI = 0.84-2.99). The frequency of the GSTM1 (0/0) genotype was also higher in patients with advanced stage disease. In stage D, the OR was 1.7 with a CI of 0.93-3.17 and in stages A and B, the OR was 0.8 with a CI of 0.40-1.62. CONCLUSIONS: These results suggest that CYP1A1 and GSTM1 polymorphisms are linked to a propensity for PCa development.      

Association between glutathione S-transferase M1 null variant and risk of bladder cancer in Chinese Han population

Glutathione S-transferase M1 (GSTM1) is one of the most important families of phase II isoenzymes known to detoxify a variety of electrophilic compounds and carcinogens. The GSTM1 null variant is associated with decreased enzyme activity, and it has been assumed to be associated with bladder cancer. The association between the GSTM1 null variant and bladder cancer in the Chinese Han population was unclear owing to the obvious inconsistency from published studies. To quantify the association between the GSTM1 null variant and bladder cancer in the Chinese Han population, we carried out the meta-analysis. We estimated the pooled odds ratio (OR) with its 95 % confidence interval (95 % CI) to assess the association. Eight studies with a total of 3,887 individuals were finally included into the meta-analysis. Overall, there was an obvious association between the GSTM1 null variant and risk of bladder cancer in the Chinese Han population (OR?=?1.61, 95 % CI 1.41–1.84, P?<?0.001). There was no heterogeneity across those eight studies (I ²?=?0 %). The cumulative meta-analyses showed a trend of more obvious association between the GSTM1 null variant and risk of bladder cancer in the Chinese Han population as data accumulated by year. There was no obvious evidence of publication bias in the meta-analysis. In conclusion, the GSTM1 null variant is significantly associated with risk of bladder cancer in the Chinese Han population.     

Lack of interaction between asbestos exposure and glutathione S-transferase M1 and T1 genotypes in lung carcinogenesis.

An interaction between occupational carcinogens and genetic susceptibility factors in determining individual lung cancer risk is biologically plausible, but the interpretation of available studies are limited by the small number of exposed subjects. We selected from the international database on Genetic Susceptibility and Environmental Carcinogens the studies of lung cancer that included information on metabolic polymorphisms and occupational exposures. Adequate data were available for asbestos exposure and GSTM1 (five studies) and GSTT1 (three studies) polymorphisms. For GSTM1, the pooled analysis included 651 cases and 983 controls. The odds ratio (OR) of lung cancer was 2.0 [95% confidence interval (CI) 1.4-2.7] for asbestos exposure and 1.1 (95% CI 0.9-1.4) for GSTM1-null genotype. The OR of interaction between asbestos and GSTM1 polymorphism was 1.1 (95% CI 0.6-2.1) based on 54 cases and 53 controls who were asbestos exposed and GSTM1 null. The case-only approach, which was based on 869 lung cancer cases and had an 80% power to detect an OR of interaction of 1.56, also provided lack of evidence of interaction. The analysis of possible interaction between GSTT1 polymorphism and asbestos exposure in relation to lung cancer was based on 619 cases. The prevalence OR of GSTT1-null genotype and asbestos exposure was 1.1 (95% CI 0.6-2.0). Our results do not support the hypothesis that the risk of lung cancer after asbestos exposure differs according to GSTM1 genotype. The low statistical power of the pooled analysis for GSTT1 genotypes hampered any firm conclusion. No adequate data were available to assess other interactions between occupational exposures and metabolic polymorphisms.     

Effects of glutathione S-transferase (GST) M1 and GSTT1 genotypes on urothelial cancer risk.

The M1 member of the mu class of the glutathione S-transferase (GSTM1) gene is present in about 50% of individuals. GSTT1, a member of the theta class, which has been recently shown to be polymorphic, is expressed in 35-90% of individuals. In this study, 145 Japanese patients with urothelial transitional cell carcinoma and 145 healthy controls, frequency-matched for age and gender, were compared for frequencies of GSTM1 and GSTT1 genotypes. The urothelial cancer risk increased due to the GSTM1 null genotype (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.05-2.79). On the other hand, the OR tended to decrease due to the GSTT1 null genotype, although not significantly. Among individuals of the GSTM1 null genotype, those of the GSTT1-positive genotype had a two-fold risk (OR 2.62, 95% CI 1.36-5.05) compared with the GSTT1 null genotype (OR 1.25, 95% CI 0.62-2.51). A significant interaction between the GSTM1 genotype and smoking status was found; the GSTM1 null genotype was associated with an increased risk of urothelial cancer among smokers (OR 1.98, 95% CI 1.10-3.57).     

Genotypes of glutathione S-transferase M1 and N-acetyltransferase 2 in Japanese patients with gastric cancer

Background. Genetic polymorphisms of some metabolizing enzymes, such as glutathione S-transferase M1 ( GSTM1 ) and N-acetyltransferase 2 ( NAT2 ), have recently been shown to affect individual susceptibility to various types of cancers. However, the link between the GSTM1 polymorphism and gastric cancer is controversial and there are few studies focusing on the relation between a combination of the two enzyme genotypes and gastric cancer risk. Methods. Genotypes of GSTM1 and NAT2 were determined by polymerase chain reaction (PCR) or restriction fragment length polymorphism (RFLP) following PCR in 147 Japanese patients with gastric cancer and 112 autopsied Japanese patients without stomach, lung, urinary bladder, or colon cancer. Results. The frequency of the GSTM1 null genotype was significantly increased in the cancer patients (91 individuals; 61.9%) compared with the controls (55 individuals; 49.1%) ( P < 0.05; odds ratio, 1.68). The incidence of patients with the homozygously wild genotype of NAT2 (rapid acetylator) was slightly lower in the cancer group (59 individuals; 40.1%) than in the control group (58 individuals; 51.8%). The proportion of patients with both the GSTM1 gene and homozygously wild genotype of NAT2 was significantly smaller in the cancer group (19 individuals; 12.9%) than in the control group (29 individuals; 25.9%) ( P < 0.05). In addition, in a comparison of four subgroups of gastric cancer which were classified by both the genotype of GSTM1 and the predicted phenotype of NAT2, the number of subjects in the subgroup " GSTM1 +/rapid" was significantly smaller than the expected numbers of the other three subgroups ( P < 0.05). Conclusion. It is suggested that a combination of GSTM1 and NAT2 decreases the risk of gastric cancer in Japanese patients. Received for publication on June 1, 1999; accepted on Aug. 6, 1999     

Reproductive factors,glutathione S-transferase M1 and T1 genetic polymorphism and breast cancer risk

We conducted a hospital-based case–control study to evaluate the interactive effect of reproductive factors and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in individual susceptibility to breast cancer. The study population consisted of 189 incident breast cancer cases and 189 age-matched controls with no known malignant diseases. GSTM1/T1 genotypes were determined by a multiplex polymerase chain reaction (PCR) method, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression model. The parity factors were grouped as (1) high-risk status defined as nullipara or para with experience of first full-term pregnancy (FFTP) at or over 30 years, and (2) low-risk status defined as para with experience of FFTP under 30 years. A significant multiplicative interaction was observed between GSTM1 and GSTT1 null genotypes and high-risk status of parity factor in all women and in premenopausal women (P 0.01), but not in postmenopausal women (P > 0.05). The interaction between the combined genotypes of GSTM1 and GSTT1 and status of parity factor was also significant in all women and in premenopausal women (P < 0.01). Our findings suggest that genetic polymorphisms GSTM1/T1 could modify estrogen-related breast cancer risk.     

Association between glutathione S-transferase T1 null genotype and glioma susceptibility: a meta-analysis

The relationship between genetic polymorphisms of glutathione S-transferase (GST) and the development of glioma has been investigated in several epidemiologic studies. However, these studies report inconsistent results. In order to get this precise result, a meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95 % confidence intervals (95 % CI). Eleven case–control research studies with a total of 2,416 glioma cases and 4,850 controls were included into this meta-analysis. The combined results based on all studies showed that there was no significant association between the GSTT1 null allele and glioma risk (OR?=?1.188, 95 % CI?=?0.929–1.520, P _{heterogeneity}?=?0.003, P?=?0.170). In the subgroup analysis, the same results were found in our work. There was no risk of publication bias in this meta-analysis. Our results suggest that GSTT1 null genotype was not associated with the increased risk of glioma.     

Association between glutathione S-transferase T1 null genotype and risk of lung cancer: a meta-analysis of 55 studies

The relationship between glutathione S-transferase T1 (GSTT1) gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between GSTT1 polymorphism and the risk of lung cancer. A comprehensive research was conducted through the databases, and 55 studies were recruited into this meta-analysis for the association of null genotype of GSTT1 with lung cancer susceptibility, consisting of 15,140 patients with lung cancer and 16,662 controls. There was a significant association between GSTT1 null genotype and lung cancer risk in the overall populations (OR?=?1.138, 95 % CI?=?1.032–1.255, P _{heterogeneity}?=?0.000, P?=?0.009). Furthermore, GSTT1 null genotype was associated with the lung cancer risk in Asians (OR?=?1.469, 95 % CI?=?1.228–1.757, P _{heterogeneity}?=?0.000, P?=?0.000). However, GSTT1 null genotype was not associated with the risk of lung cancer in Caucasians and Africans. In conclusion, GSTT1 null genotype is associated with the lung cancer in overall populations and in Asians.     

The glutathione S-transferase M1 genotype in ovarian cancer.

Glutathione S-transferase mu-1 (GSTM1) is a polymorphic member of the mu class gene family of the glutathione S-transferases. Individuals who are GSTM1 null have increased susceptibility to lung and colon cancer. We hypothesized that: (a) GSTM1 null individuals might also be at increased risk for development of ovarian cancer; and (b) the GSTM1 genotype would influence response to chemotherapy. One hundred and forty-six individuals with invasive epithelial ovarian cancer were genotyped using a three-primer PCR reaction specific for the GSTM1 gene and an internal control glutathione S-transferase mu-4 (GSTM4). The products were analyzed on agarose gels. Healthy individuals without a family history of ovarian, breast, or colon cancer served as unmatched controls (n = 80). The results show that age at diagnosis, histological type, and stage of ovarian cancer were all independent of GSTM1 genotype. The frequency of the GSTM1 null genotype in the ovarian cancer cohort was similar to that in the control population, 51% versus 58%, P > 0.05. Likewise, median survival for individuals with advanced stage ovarian cancer was independent of GSTM1 genotype. We concluded that the GSTM1 null genotype does not increase ovarian cancer risk. These findings suggest that GSTM1 does not play a significant role in detoxifying environmental factors that influence ovarian carcinogenesis and does not play an important role in the resistance of ovarian cancer to chemotherapy.     

Glutathione S-transferase M1 and T1 null genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/tobacco chewers.

Oral cancer is the most common cancer in males and third most common in females in India, the main causative agent being the use of chewing tobacco with or without betel quid (BQ). However, nothing is known about the role of the host metabolic genes in oral cancer in ethnic Indian population. In this study, the prevalence of GSTM1 and GSTT1 null genotypes (GSTM1*2 and GSTT1*2) in oral premalignant leukoplakia cases and controls was ascertained in genomic DNA by a multiplex PCR technique. Biopsies taken from 98 oral leukoplakia patients and exfoliated cells from 82 healthy controls both of Indian ethnicity were analysed. GSTM1*1 (active) was present in 83% and GSTT1*1 (active) was present in 78% of all control subjects, while prevalence of GSTM1*2 and GSTT1*2 null genotypes was significantly higher among oral leukoplakia cases. The prevalence of GSTM1*2 in leukoplakia cases was 81.6% compared with 17% in controls [odds ratio (OR), 22; 95% confidence interval (CI), 1047] and GSTT1*2 was 75.5% in the cases versus 22% in controls (OR, 11; 95% CI, 5-22). Combined null genotypes of GSTM1 and GSTT1 prevailed in 60.2% of the cases with none detected in controls. Glutathione S-transferase M1 and T1 enzymes are both known to catalyse detoxification of reactive oxygen species, lipid peroxidation products and tobacco-derived carcinogens that have been found in the saliva of BQ/tobacco chewers. Our results, still requiring confirmation by a larger study, demonstrate that the null genotypes of both GSTM1 and GSTT1 increase with high penetrance, separately or in combination, the risk for developing leukoplakia in an Indian ethnic population.     

Interactive effect of glutathione S-transferase M1 and T1 polymorphisms on hepatocellular carcinoma

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) have been involved in the risk of hepatocellular carcinoma (HCC). However, the interactive effect of GSTM1 and GSTT1 has not been reported previously. The aim of this work was to investigate the interaction and synergism of their variants. We identified nine publications including 1,085 cases and 2,396 controls containing both GSTM1 and GSTT1, and the bi-factor variance analysis of equal repeated test, binary class logistic regression analysis, meta-analysis and probability method were used in this analysis. Data showed there was no interaction between GSTM1 and GSTT1 null genotype variation in HCC development. In addition, individuals with at least one null genotype of GSTM1 and GSTT1 had higher susceptibility to HCC (OR?=?2.99, 95 % CI 2.21–4.02). In the control group, the probability of individuals with at least one null genotype of GSTM1 and GSTT1 was 0.6624, while in the case group, the probability to develop HCC with at least one null genotype of GSTM1 and GSTT1 increased to 0.1760, which was considered as the changing characteristics of HCC occurrence in Chinese population. Our result suggests that there would be no direct interaction of GSTM1 and GSTT1 genotype in HCC risk. We speculate that GSTM1 and GSTT1 genotype variations have their own independent function in HCC development and may mutate independently to cause HCC. The synergism variants of the two genes in HCC development have bigger risk in Chinese population.     

Glutathione S-transferase M1 and T1 null genotype frequency in chronic myeloid leukaemia.

Polymorphisms associated with genes coding for glutathione S-transferase enzymes are known to influence metabolism of different carcinogens and have been associated with incidence of various types of cancer. We have determined the GST M1 and GST T1 'null' genotype frequency in 81 patients with chronic myeloid leukaemia (CML) and 123 racially and geographically matched control individuals by multiplex polymerase chain reaction (PCR). GST M1 null genotype frequencies in CML and controls were 28.4% and 27.7%, respectively. GST T1 null genotype frequencies in CML and controls were 19.8% and 7.3%, respectively. The GST T1 null genotype frequency in CML patients is significantly different from that in controls (odds ratio (OR) 3.12, 95% confidence interval (CI) 1.3-7.45, P=0.008).