GSTT1 Gene Polymorphisms Research Articles

GSTM1 and GSTT1 gene polymorphisms as major risk factors for bronchopulmonary dysplasia in a Chinese Han population

Bronchopulmonary dysphasia (BPD) is a complex multifactorial disease with an obvious genetic predisposition. Oxidative stress plays an important role in its pathogenesis. Glutathione S-transferases (GSTs) detoxify metabolites produced by oxidative stress within the cell and protect the cells against injury. In the present study, the hypothesis that polymorphisms in the GSTM1 and GSTT1 genes are associated with BPD in Chinese Han infants was examined. Sixty infants with BPD and 100 gestational age and birth weight-matched preterm infants without BPD were recruited. Genotyping for GSTM1 and GSTT1 was performed by multiplex polymerase chain reaction (PCR). The GSTM1 null genotype was more prevalent in BPD infants (65.0%) than in the control subjects (48.0%), which yielded higher risk towards BPD (odds ratio (OR): 2.012, 95% confidence interval (CI)=1.040–3.892, p=0.037). There was no statistically significant association of GSTT1 genotype with BPD (OR: 1.691, 95% CI=0.884–3.236, p=0.111), although the frequency of GSTT1 null genotype was higher among the BPD subjects (60.0%) than in the control patients (47.0%). GSTM1 and GSTT1 double null genotype was also higher in BPD group (38.3%) than in controls (21.0%) with a higher risk towards BPD (OR: 2.338, 95%CI=1.151–4.751, p=0.017). The results suggest that null genotypes of GSTM1 and GSTT1 genes may contribute to the development of BPD in our Chinese Han population.

Cytogenetic Damage in Turkish Coke Oven Workers Exposed to Polycyclic Aromatic Hydrocarbons: Association with CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 Gene Polymorphisms

The aim of this study was to determine the frequencies of chromosomal aberrations (CA) and cytochalasin-blocked micronuclei (CBMN) in peripheral blood lymphocytes from Turkish coke oven workers and the influence of CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 gene polymorphisms on these biomarkers. Cytogenetic analysis showed that occupational exposure significantly increased the CA and CBMN frequencies. Gene polymorphisms, on the other hand, did not affect CA or CBMN in either exposed or control subjects. However, due to the limited sample size, our findings need to be verified in future studies with a larger sample.

The glutathione S-transferase T1 deletion is associated with susceptibility to multiple sclerosis

BackgroundMultiple sclerosis (MS) occurs as a result of interaction between genetic and environmental factors. Recent data support the view that oxidative damage is one of an early event in MS tissue injury. The safe elimination of reactive oxygen species and toxins via glutathione S-transferase (GST) pathways is required in order to protect cells against reactive oxygen-induced damage. The aim of our study was to analyze the possible association of GSTM1 and GSTT1 gene polymorphisms with the susceptibility and clinical parameters of MS, in 455 consecutive patients and 366 controls. MethodsA multiplex polymerase chain reaction (PCR) was used to detect the deletions in GSTM1 and GSTT1 genes. ResultsPatients with MS had significantly higher frequency of GSTT1 null genotype compared to controls (37.36% vs. 21.86%, respectively, p<0.0001, adjusted OR 2.13 (1.56–2.90)), as well as double deletions (15.38% vs. 10.38%, respectively, p<0.05). The carriers of GSTM1 deletion had significantly earlier onset of MS compared to the wild-type carriers (28.31±8.45 vs. 30.64±9.30years, respectively, p=0.03). ConclusionThis study suggests the potential pathogenic role of GSTT1 deletion on MS susceptibility. There are no similar data published so far, yet this study should be replicated in other populations.

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 involved in phase II of carcinogen detoxification have been frequently studied in the literature. Their null genotypes are thought to be associated with increased head and neck cancer risk. However, the published reviews are not up to date and many important papers have been skipped. The current literature review was restricted to the null genotypes of the GSTM1 and GSTT1 genes with special emphasis on the genotypic status. We found that the size of study sample varied greatly and the oral cavity cancer was more influenced by GSTM1 and GSTT1 gene deletions. With respect to ethnicity Asians are more prone to head and neck cancers with these null genotypes as compared 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. Review confirms the data of previous reviews that GSTM1 and GSTT1 gene polymorphisms may be risk factors for cancer initiation.

CYP1A1 (Ile462Val), CYP1B1 (Ala119Ser and Val432Leu), GSTM1 (null), and GSTT1 (null) Polymorphisms and Bladder Cancer Risk in a Turkish Population

We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

Association between the polymorphisms of glutathione S-transferase genes and rheumatoid arthritis: A meta-analysis

The glutathione S-transferases (GSTs) are a family of phase II xenobiotic metabolizing enzymes known to be involved in the detoxification and elimination of reactive oxygen species (ROS), thus defending tissues against oxidative stress. Recently, several studies have examined the potential contributions of GSTM1 and GSTT1 gene polymorphisms toward susceptibility to rheumatoid arthritis (RA), but these studies have produced diverse results. To verify the association between GSTM1 and GSTT1 gene polymorphisms and susceptibility to RA, we conducted a meta-analysis of all relevant reports cited in MEDLINE/PubMed before April 2012. A meta-analysis on the association between the GSTM1 polymorphism and RA was performed for 4636 patients with RA and 3916 controls from 8 published studies. In addition, a total of 5 studies involving 3174 RA patients and 2958 controls were considered in the meta-analysis of the association between the GSTT1 polymorphism and RA. No significant association was found between the GSTM1 null genotype and RA susceptibility in all subjects; however, a significant increased risk was found in East Asians. The GSTT1 null genotype was not associated with susceptibility to RA in any study subject. No apparent effect of smoking was found in stratified analysis. The results of our meta-analysis indicated that the GSTM1 null genotype is significantly associated with RA in East Asians alone, indicating that GSTM1 is another non-human leukocyte antigen (non-HLA) susceptibility gene for RA in East Asian populations.

Association of GSTT1 gene polymorphisms with the risk of prostate cancer: an updating meta-analysis

It has been demonstrated that the glutathione S-transferase (GST) superfamily helps remove carcinogens from the body and thus might be associated with prostate cancer risk. In recent years, GSTT1 polymorphism has been extensively studied as a potential prostate cancer risk factor; however, the results are inconsistent. To investigate the association between GSTT1 and prostate cancer, we conducted a meta-analysis of 33 studies with 6,697 prostate patients and 7,643 controls. For GSTM1 null versus present genotype, the random effects odds ratio was 0.98 (95 % confidence interval (CI) 0.83-1.16) based on a wide population. Subgroup analyses in the different ethnic groups and different controls were performed. The OR was 1.01 (95 % CI 0.86-1.19) in Caucasians, 1.01 (95 % CI 0.70-1.47) in Asians, and 0.77 (95 % CI 0.42-1.42) in Africans. The OR was 0.98 (95 % CI 0.82-1.16) in non-benign prostate hyperplasia (BPH) controls and 1.09 (95 % CI 0.66-1.79) in BPH controls. In conclusion, our present meta-analysis demonstrates that there is no association between GSTT1 polymorphism and prostate cancer, even in the sub-analysis concerning different races and control sources. The direction of further research should focus not only on the simple relationship of GSTT1 and prostate cancer but also on gene-environment interaction and distinctions of different GSTs.

No association between the GSTM1 and GSTT1 polymorphism and endometrial cancer risk: A meta-analysi

Purpose: A number of case-control studies have been conducted to investigate the association of glutathione S-transferase (GST) genetic polymorphisms and endometrial carcinoma risk. However, these studies have yielded contradictory results. We therefore performed a meta-analysis to derive a more precise estimation of the association between polymorphisms on GSTM1, GSTT1 and endometrial carcinoma. Methods: Identification of relevant studies was carried out through a search in the following databases Medline, EMbase andChinaNational Knowledge International (CNKI) up to March. 2013. All case-control studies that investigated the association between GS-TM1 and GSTT1 gene polymorphisms and risk of endometrial cancer were included in the study. The pooled odds ratio (OR) was used for analyses of results and the corresponding 95% confidence intervals (CI) were estimated. Result: Six published case-control studies of association between the GSTM1 and GSTT1 polymorphism and endometrial cancer risk covering 3558 subjects were included in the metaanalysis, but the results indicated that the null genotypes of GSTM1 and GSTT1 polymorphisms were not associated with a significantly increased risk of endometrial cancer (for GSTM1: OR = 0.99; 95% CI, 0.86 - 1.4; for GSTT1: OR = 0.96; 95% CI, 0.80 - 1.14, respectively). Conclusion: This meta-analysis suggests that GSTM1 and GSTT1 polymorphism may not be associated with increased risk of endometrial cancer. To validate the association between polymorphism and endometrial cancer, further studies with larger numbers of participants worldwide are needed.

Erratum to: Dependence of Blood Levels of HSP70 and HSP90 on Genotypes of HSP70, GSTT1, and GSTM1 Gene Polymorphism in Individuals Chronically Exposed to Mercury

Erratum to: Dependence of Blood Levels of HSP70 and HSP90 on Genotypes of HSP70, GSTT1, and GSTM1 Gene Polymorphism in Individuals Chronically Exposed to Mercury

Glutathione S-transferase M1 and T1 genotypes and myocardial infarction

Myocardial infarction (MI), which is the most important manifestation of coronary artery disease, is the leading cause of morbidity and mortality in the world. Glutathione S transferases (GSTs) are enzymes responsible for the metabolism of numerous xenobiotics and are known to be polymorphic in humans. We investigated the association between the GSTM1 and GSTT1 gene polymorphisms and MI. The study consists of 296 healthy controls and 324 consecutive patients who had undergone coronary angiography for suspicion of coronary artery disease and with a past history of myocardial infarction. DNA was extracted from whole blood of patient and control. GSTM1 and GSTT1 gene polymorphisms were examined using multiplex PCR. We found that the null GSTM1 was associated with protective effect on MI, although this increase was not significant for GSTM1 (p < 0.054). However, GSTT1 genotype was associated with an increase in the risk of developing MI. In addition to after adjusting other all coronary risk factors, the interactive effect of GSTT1 null genotype remained statistically significant (p < 0.001) for MI disease but GSTM1 null genotype was not statistically significant. Patients, who smoke having the null genotypes of GSTM1, were at a higher risk for developing MI (p < 0.001, OR = 0.41, 95 % CI = 0.240-0.207). There was an effect of interaction of GSTM1 null genotype and smoking on MI development between patient and control groups (p < 0.001). Our results showed that individuals with the null genotypes for GSTM1 had protective effect, while GSTT1 was at a higher risk for MI disease. In addition, there was additional effects of smoking when smoking and non-smoking groups were compared.

Association of mitochondrial D-loop mutations with GSTM1 and GSTT1 polymorphisms in oral carcinoma: A case control study from Northeast India

Mitochondrial dysfunction is a hallmark of cancer cells. Tobacco consumption in various forms is one of the major risk factors for the development of oral squamous cell carcinoma which makes the mitochondrial DNA susceptible to damage by reactive oxygen species. The GSTT1 and GSTM1 members of the glutathione S-transferase multigene family are candidate carcinogen metabolizing genes. Here we determined the hot spot mutations in the D-loop region and revealing correlation if any, with clinical parameters, along with analysing the genetic polymorphism of GSTT1 and GSTM1 and its susceptibility towards oral cancer. To determine the hot spot mutations 25 matched tissue samples of OSCC patients with 25 control subjects were used for PCR and direct sequencing. Analysis for GSTM1 and GSTT1 gene polymorphism was done by multiplex PCR. Several mutations were found within the D-loop region among which mutations at nt146, nt152 and nt196 are found to be hot spot (P<0.0001, P<0.0001 and P<0.001 respectively). A significant association was found between the numbers of D-loop mutation and GSTM1 (OR=2.03; 95% CI, 1.04-3.96, P=0.003), GSTT1 (OR=1.73; 95% CI, 1.10-2.71, P=0.0027) null genotypes respectively. We observed a significant correlation between the increased number of D-loop mutations with the advancement in tumour stage of the patients (P=0.009, r=0.48). The association of null genotypes and mutations can be used as a possible biomarker for early detection and preventive measure of oral cancer for those habituated to tobacco consumption.

Association of the Glutathione S-transferases M1 and T1 polymorphism with male infertility: a meta-analysis

Genes of different pathways regulate spermatogenesis, and the complexity of the spermatogenic process indicates that polymorphisms or mutations in these genes could cause male infertility. Published data on the association between the GSTM1 and GSTT1 polymorphism and male infertility risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 11 studies regarding GSTM1 and 9 studies regarding GSTT1 between 1999 and 2012 were identified through researching MEDLINE, EMBASE and the Chinese Biomedical Database. It was performed to obtain summary estimated odd ratios and 95 % confidence intervals of GSTM1 and GSTT1 for male infertility, with attention to study quality and publication bias. Overall, a significant association was seen between GSTM1 (OR=1.20, 95 % CI=1.02-1.40, P(heterogeneity) =0.000, P=0.027) genotypes and male infertility. Significant associations were also observed in subgroups of Caucasian populations (OR=1.65, 95 %CI=1.16-2.34, P(heterogeneity) =0.006, P=0.005), but were not observed in Asian populations (OR=1.09, 95 % CI=0.72-1.65, P(heterogeneity) =0.054, P=0.697) when stratified by ethnicity. While there was no significant association was seen between GSTT1 (OR=1.00, 95 % CI=0.74-1.35, P(heterogeneity) =0.000, P=0.980) null genotypes and male infertility. Simultaneously, significant associations were not observed in subgroups of Caucasian populations (OR=0.94, 95 %CI=0.44-2.00, P(heterogeneity) =0.000, P=0.867) and Asian populations (OR=0.93, 95 % CI=0.46-1.87, P(heterogeneity) =0.002, P=0.838) when stratified by ethnicity. Our results suggest the GSTM1 null genotype contributes to male infertility susceptibility, while GSTT1 gene polymorphisms are not associated with male infertility in our study.

Low level maternal smoking and infant birthweight reduction: genetic contributions of GSTT1 and GSTM1polymorphisms

BackgroundGenetic susceptibility to tobacco smoke might modify the effect of smoking on pregnancy outcomes.MethodsWe conducted a case–control study of 543 women who delivered singleton live births in Kaunas (Lithuania), examining the association between low-level tobacco smoke exposure (mean: 4.8 cigarettes/day) during pregnancy, GSTT1 and GSTM1 polymorphisms and birthweight of the infant. Multiple linear-regression analysis was performed adjusting for gestational age, maternal education, family status, body mass index, blood pressure, and parity. Subsequently, we tested for the interaction effect of maternal smoking, GSTT1 and GSTM1 genes polymorphisms with birthweight by adding all the product terms in the regression models.ResultsThe findings suggested a birthweight reduction among light-smoking with the GSTT1–null genotype (−162.9 g, P = 0.041) and those with the GSTM1–null genotype (−118.7 g, P = 0.069). When a combination of these genotypes was considered, birthweight was significantly lower for infants of smoking women the carriers of the double-null genotypes (−311.2 g, P = 0.008). The interaction effect of maternal smoking, GSTM1 and GSTT1 genotypes was marginally significant on birthweight (−234.5 g, P = 0.078). Among non-smokers, genotype did not independently confer an adverse effect on infant birthweight.ConclusionsThe study shows the GSTT1–null genotype, either presents only one or both with GSTM1–null genotype in a single subject, have a modifying effect on birthweight among smoking women even though their smoking is low level. Our data also indicate that identification of the group of susceptible subjects should be based on both environmental exposure and gene polymorphism. Findings of this study add additional evidence on the interplay among two key GST genes and maternal smoking on birth weight of newborns.

Dependence of Blood Levels of HSP70 and HSP90 on Genotypes of HSP70, GSTT1, and GSTM1 Gene Polymorphism in Individuals Chronically Exposed to Mercury

The relationship between blood levels of HSP72, HSP72+HSP73, and HSP90 and genotypes of three polymorphisms of the HSP70 family, HSPA1L (2437T/C) and HSPA1B (2074G/C and 1267A/G) as well as GSTT1 and GSTM1 polymorphisms was studied in 82 men chronically exposed to mercury. Of these, 40 men were exposed to mercury for more than 10 years (group 1) and 42 developed chronic mercuric intoxication (group 2). The groups differed significantly by TT (p=0.004) and TC (p=0.007) genotypes of HSPA1L gene locus 2437T/C. Differences in the heat shock protein content associated with HSP70 gene polymorphism were detected only for HSPA1B gene locus 2074G/C and consisted in reduction of HSP90 (p=0.020) and HSP72 (p=0.056) for GG genotype in group 2 in comparison with group 1. Combination of GSTT1(+)/GSTM1(0/0) genotypes was associated with reduction of the protein levels, while variants including GSTT1(0/0) were associated with a significant elevation thereof.

Reporting Genetic Association Studies: The Roadblocks and Guiding Rules for Robust Results

Congratulations to Dr. Birbian and colleagues for their article ‘‘GSTT1 and GSTM1 Gene Polymorphisms as Major Risk Factors for Asthma in a North Indian Population’’ [1]. Theirs was the first published study on GSTT1 and GSTM1 genetic polymorphisms in a north Indian population using a case–control design. The study was carried out on a good sample size and a number of conclusions were drawn. However, we felt that the authors should have followed the international guidelines for reporting genetic association studies (STREGA) [2] to add lasting value to their findings. Case–control association studies are valiant way to detect associations in a resource-limited setting, but in reporting the results of such studies there are several roadblocks that must be cleared and addressed before arriving at robust and useful conclusions. The ultimate goal of all such studies is to arrive at very futuristic individualized medicine and an immunotherapeutic approach to disease. Transparency and accuracy of the reported results of medical research must be ensured to enhance the value of such studies. The formation of the STrengthening the REporting of Genetic Association (STREGA) studies guidelines was a significant step in that direction; they were published in many journals simultaneously [2]. There are a number of considerations but three of the most important that have been shown time and again to be of great value are as follows:

Relevance of GSTM1, GSTT1, and GSTP1 gene polymorphisms to gastric cancer susceptibility and phenotype

Human glutathione S-transferases (GSTs) are phase II metabolizing enzymes that play a key role in protecting against cancer by detoxifying numerous potentially cytotoxic/genotoxic compounds. The genes encoding the human GST isoenzymes GSTM(mu)1, GSTT(theta)1 and GSTP(pi)1 harbour polymorphisms, which have been considered important modifiers of the individual risk for environmentally induced cancers such as gastric cancer (GC). However, results are inconsistent among studies from different geographic areas and ethnic groups. Our goal was to perform a nationwide, case-control study in Spain to evaluate the relevance of several functional GST gene polymorphisms and environmental factors to GC risk and phenotype. DNA from 557 GC patients and 557 sex- and age-matched healthy controls (HC) was typed for two deletions in the GSTM1 and GSTT1 genes and two SNPs in the GSTP1 gene (rs1695 and rs1138272) using polymerase chain reaction-restriction fragment length polymorphism methods. Logistic regression analysis identified Helicobacter pylori infection with CagA strains [odds ratio (OR): 2.36; 95% confidence interval (CI): 1.78-3.15], smoking habit (OR: 2.10; 95% CI: 1.48-2.97) and family history of GC (OR: 3.2; 95% CI: 2.02-5.16) as independent risk factors for GC. No differences in the frequencies of GSTM1 or GSTT1 null genotypes were observed between cases and controls (GSTM1: 50.8% vs. 48%; GSTT1: 21.5% vs. 21%). Moreover, simultaneous carriage of both, the GSTM1 and the GSTT1 null genotypes, was almost identical in both groups (10.7% in GC vs. 10.6% in HC). In addition, no significant differences in GSTP1 Ile105Val (rs1695) and GSTP1 Val114Ala (rs1138272) genotype distribution were observed between GC patients and controls. Subgroup analysis for age, gender, Helicobacter pylori status, smoking habits, family history of GC, anatomic location and histological subtype revealed no significant association between GST variants and GC risk. Our results show that the GST polymorphisms evaluated in this study are not relevant when determining the individual susceptibility to GC or phenotype in a South-European population.

Allelic variation of GSTM1 and GSTT1 genes in Haryana population

The glutathione S-transferase mu (GSTM1) and theta (GSTT1) members of the GST multigene family are polymorphic in human populations, and homozygous deletions or null genotypes of GSTT1 and GSTM1 genes have been reported in different populations. Epidemiological studies suggest that individuals who are homozygous null at the GSTM1 or GSTT1 loci may have an increased risk of cancer; therefore, the distribution of these genotypes in the human population is of great interest. The aim of our study was to investigate the allelic variations of GSTM1 and GSTT1 genotypes in 308 healthy, unrelated individuals from the state of Haryana in India. The participants were genotyped for the presence of GSTM1 and GSTT1 genes using the multiplex polymerase chain reaction (PCR) technique. On the basis of the results from our findings, we found that, in the geographic region of our study (India), 40.58% of individuals are carriers of the GSTM1 0/0 (null) genotype, whereas 32.79% of individuals have the GSTT1 0/0 (null) genotype. This study contributes significant information on the variability of GSTT1 and GSTM1 gene polymorphisms in the worldwide population and could increase knowledge about the relationship between ethnicity and the prevalence of certain diseases.

Assessment of Individual Susceptibility to Baseline DNA and Cytogenetic Damage in a Healthy Turkish Population: Evaluation with Lifestyle Factors

Cytogenetic biomarkers are most frequently used well-established endpoints in human population studies with their sensitivity for measuring exposure to genotoxic agents. They have an important role as early predictors of cancer risk. Identification of individual genotypes of metabolic gene polymorphisms helps to understand the modulation of cancer susceptibility by environmental exposures, such as cigarette smoking and other lifestyle factors. To evaluate individual susceptibility to chemicals, we determined individual DNA damage related to glutathione S-transferase (GST) genotypes (GSTM1, GSTT1, and GSTP1) in a Turkish population. Peripheral blood lymphocytes (PBL) and DNA samples of 127 subjects were analyzed for the presence of DNA damage, using single-cell gel electrophoresis (the Comet assay), and for cytogenetic parameters (chromosomal aberrations [CAs], bleomycin-induced CA, and a cytokinesis-blocked micronucleus assay), and the polymerase chain reaction/restriction fragment length polymorphism method, respectively. Individuals carrying a GSTT1-null allele showed higher frequencies of CA and micronucleus (MN) (p=0.026, p=0.003, respectively), whereas the GSTM1-null and GSTP1 mutant genotypes did not show any differences in cytogenetic parameters. Our findings demonstrated that none of the lifestyle factors (smoking, alcohol drinking, dietary habits, vitamin intake, and physical activity), except for vitamin intake (p=0.002), were significantly associated with the studied cytogenetic parameters. Our results suggest that the GSTT1 gene polymorphism may influence the baseline cytogenetic frequency in a healthy population.

Polymorphisme génétique des glutathion-s-transférases GSTM1 et GSTT1 et survenue d’un cancer colorectal dans un échantillon de la population tunisienne

Individual susceptibility to colorectal cancer (CRC) may be partly due to genetic differences in detoxification and/or activation of xenobiotics. This study was carried out pointing GSTT1 and GSTM1 polymorphisms on the risk of CRC development. Taking into account the important impact of diet in CRC development and prevention, this study explored the correlation of certain foods (fast food, fish, salami, red meat and poultry) with CRC occurrence. Ninety-one patients and 127 controls from the Tunisian population, all from the Sahel region, were enrolled in this study. No association between the GSTM1 gene polymorphism and the CRC was found. However, an association between the GSTT1 gene polymorphism and the risk of CRC was encountered (P = 0.039, OR = 0.53, CI: 0.29–0.97). Our results revealed a significant correlation between fast food consumption and CRC occurrence (P = 0.00015; correlation coefficient = 0.258), whereas fish consumption was inversely correlated to CRC incidence (P = 0.049; correlation coefficient = −0.136). In conclusion, the homozygous null GSTT1 gene may be considered as a protective factor CRC onset. Unlike fast food consumption, fish consumption appeared to be a protector factor. La susceptibilité individuelle au cancer colorectal (CCR) pourrait être en partie expliquée par des différences génétiques dans la détoxification et/ou l’activation des xénobiotiques. Tout en tenant compte du rôle particulier de l’alimentation dans le développement et la prévention du cancer, s’est réalisé ce travail qui s’est intéressé à l’étude de l’incidence des polymorphismes GSTT1 et GSTM1 sur le risque de développement du CCR et a exploré la corrélation de certains aliments avec la survenue de cette pathologie. Ce travail a été porté sur l’étude d’une population tunisienne constituée de 94 patients et 127 témoins, tous originaires du Sahel. Aucune relation d’association entre le polymorphisme du gène GSTM1 et la survenue du CCR n’a été retrouvée. En revanche, une association entre le polymorphisme du gène GSTT1 et la survenue du CCR a été rencontrée (p = 0,039 ; OR = 0,53 ; IC : 0,29–0,97). Nous avons également étudié l’impact des habitudes alimentaires sur le risque du CCR. Nos résultats révèlent une corrélation significative entre la consommation des aliments de la restauration rapide et la survenue du CCR (p = 0,00015 ; coefficient de corrélation = 0,258) et entre la consommation des poissons et la survenue du CCR (p = 0,049 ; coefficient de corrélation = −0,136). Nous n’avons pas noté de corrélation entre la consommation des salamis, des viandes rouge et des volailles et la survenue du CCR. En conclusion, le gène homozygote nul de GSTT1 semble constituer un facteur protecteur pour le développement du CCR. Les poissons apparaîtraient comme un facteur protecteur pour la maladie tandis que la nourriture de la restauration rapide serait un facteur de risque.

Association of CYP1A1, GSTM1, and GSTT1 gene polymorphism with risk of oral submucous fibrosis in a section of North Indian population

Genetic alterations in the genes expressing drug metabolizing enzymes can make an individual susceptible to various cancers. This study detects the polymorphisms at CYP1A1, GSTM1, and GSTT1 genes in a section of North Indian population and determines the susceptibility to oral submucous fibrosis (OSF). In this case-control study one hundred and two OSF patients were genotyped to detect the GSTM1, GSTT1, CYP1A1 polymorphism. Two hundred healthy controls were also included. Genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The frequency of GSTM1 and GSTT1 genotype was higher in OSF patients, as compared to controls. A trend risk analysis showed 7.6 fold increase in risk, when both the genes were absent. The frequency of CYP1A1 (m1) and CYP1A1 (m2) genotypes was higher in controls. No polymorphic alleles were detected in the m4 site. CYP1A1 (m1) wild genotype in the absence of GSTM1 null genotype, falls under the highest risk group (OR 3.74). Our findings suggest that CYP1A1 (m1) genotype and (m2) genotype singly acts as a protective factor but in the absence of GSTM1 and/or GSTT1 gene significantly alters risk towards OSF.