Lack of association between GSTM1 and GSTT1 polymorphisms and brain tumour risk

Objective: Glutathione S-transferases (GSTs) are important enzymes that are involved in detoxification ofenvironmental carcinogens. Molecular epidemiological studies have been conducted to investigate the associationbetween GSTM1 and GSTT1 homozygous deletion polymorphisms and brain tumours but results have beenconflicting. The aim of this study was to clarify this problem using a meta-analysis. Methods: A total of 9 recordswere identified by searching the PubMed and Embase databases. Fixed- and random-effects models wereperformed to estimate the pooled odds ratios. Results: No significant association was found between the GSTM1and GSTT1 homozygous deletion polymorphisms and risk of brain tumours, including glioma and meningioma.Similar negative results were also observed in both population-based and hospital-based studies. Conclusion:These findings indicate that the GSTM1 and GSTT1 polymorphisms may not be related to the development ofbrain tumours.     

Meta-analysis of GSTM1 and GSTT1 Polymorphisms and Riskof Nasopharyngeal Cancer

Background: Studies of associations between genetic polymorphism of glutathione S-transferase M1 (GSTM1)and glutathione S-transferase T1 (GSTT1) with risk of nasopharyngeal cancer (NPC) have generated conflictingresults. Thus, a meta-analysis was performed to clarify the effects of GSTM1 and GSTT1 polymorphisms on therisk of developing NPC. Materials and Methods: A literature search in two electronic databases namely PubMedand EMBASE up to December 2012 was conducted and eligible papers were finally selected based on the inclusionand exclusion criteria. The pooled odds ratio (OR) and presence of heterogeneity and publication bias in thosestudies were evaluated. Results: A total of 9 studies concerning nasopharyngeal cancer were evaluated. Analysesof all relevant studies showed increased NPC risk to be significantly associated with the null genotypes of GSTMI(OR=1.43, 95%CI 1.24-1.66) and GSTT1 (OR=1.28, 95%CI=1.09-1.51). In addition, evidence of publication biaswas detected among the studies on GSTM1 polymorphism. Conclusions: This meta-analysis demonstrated theGSTM1 and GSTT1 null genotypes are associated with an increased risk of NPC.     

Polymorphisms of CYP1A1, GSTM1, GSTT1, and prostate cancer risk in Turkish population

Prostate cancer is the most common cancer among men in many countries. Although the etiology of prostate cancer largely is unknown, both genetic and environmental factors may be involved. Advanced age, androgen metabolism, and heredity-race have been reported to be possible risk factors. On the other hand, several studies indicate that genetic polymorphisms in biotransformation enzymes play a role in prostate cancer development. In this study, association of the prostate cancer risk with genotype frequencies of the Phase I (CYP1A1) and Phase II (GSTM1 and GSTT1) biotransformation enzymes was investigated in 321 Turkish individuals (152 prostate cancer patients and 169 age-matched male controls). The presence or absences of the GSTM1 and GSTT1 genes were determined by a PCR-based method. Genotypes of CYP1A1 were determined by MspI-RFLP. The prevalence of GSTM1 null genotype in the cases was 64 percent, compared to 31 percent in the control group, indicating a strong association (OR = 4.08, 95%CI = 2.50-6.69). No association was observed between either GSTT1 null genotype or CYP1A1 polymorphism and prostate cancer incidence. No statistically significant association was observed between smoking status of the patients and any of the polymorphisms studied. In conclusion, results of this study indicate that only the GSTM1 null genotype may play an important role as a risk factor for prostate cancer development in Turkish population.     

GSTM1, GSTT1 and GSTP1 polymorphisms and lung cancer risk

Previous studies have suggested that GST genotypes may play a role in determining susceptibility to lung cancer, though the data are often conflicting. In this study we investigated GSTM1, GSTT1 and GSTP1 status in relation to lung cancer risk in patients attending a Manchester bronchoscopy clinic. Cases were all patients (n=94) currently with, or with a history of, tumours of the lung, trachea or bronchus. The control group were all other patients (n=165) who were free of benign and malignant tumours both at the time of, or prior to, diagnosis. All patients were interviewed for information on lifestyle risk factors, and DNA extracted from bronchial lavage and blood samples was used for genotyping. GSTM1 null genotype was associated with decreased lung cancer risk (odds ratio (OR) 0.50, 95% confidence interval (CI) 0.29–0.87), particularly among men (OR 0.43, 95% CI 0.21–0.87) and those above the median age (OR 0.33, 95% CI 0.15–0.70). No difference in GSTT1 and GSTP1 genotype distribution was seen between cases and controls. The GSTM1 null genotype was associated with a decreased risk of squamous cell carcinoma: the OR, adjusted for age, sex and pack years was 0.32 (95% CI 0.12–0.82). As previous studies have reported that the GSTM1 null genotype is associated with an increased lung cancer risk, further work is required to determine whether the observed association is true, or whether it arises from bias or confounding factors.     

Distributions of the GSTM1 and GSTT1 Null Genotypes Worldwide are Characterized by Latitudinal Clines

Background: Deletion types of genetic variants of glutathione S-transferase (GST) M1 and T1, the GSTM1 nulland GSTT1 null which are risk factors for certain cancers, have been ubiquitously found in human populationsbut their worldwide distribution pattern is unclear. Materials and Methods: To perform a meta-analysis, asystematic search for the literature on GSTM1 and GSTT1 null genotypes was done to identify 63 reports for 81human populations. Relationships between the GSTM1 and GSTT1 null genotype frequencies and the absolutelatitude of 81 populations were tested by Spearman’s rank correlation coefficient. Results: A significant positivecorrelation was detected between the GSTM1 null genotype frequency and the absolute latitude (r=0.28, p-value<0.05), whereas the GSTT1 null genotype frequency and absolute latitude showed a significant negative correlation(r= -0.41 p-value <0.01). There was no correlation between the frequencies of GSTM1 and GSTT1 null genotypein each population (r= -0.029, p-value=0.80). Conclusions: Latitudinal clines of the distribution of the GSTM1and GSTT1 null genotypes may be attributed to the result of gene-environmental adaptation. No functionalcompensation between GSTM1 and GSTT1 was suggested by the lack of correlation between the null frequenciesfor GSTM1 and GSTT1.     

Allelic Variation of GSTT1, GSTM1 and GSTP1 Genes in a North Indian Population

Glutathione S-transferase (GST) enzymes are involved in detoxification of many potentially carcinogenic ‍compounds. Homozygous deletions or null genotypes of GSTT1 and GSTM1 genes and an A to G substitution at ‍nucleotide 313 in GSTP1 have been reported in different populations. Intra-ethnic as well as interethnic differences ‍are known to exist in the frequencies of the above GST genes. The present study was therefore undertaken to ‍determine the prevalence of GSTM1 and GSTT1null alleles, as well as the GSTP1 gene polymorphism, in 370 ‍healthy individuals in a North Indian population. Genotyping of M1 and T1 was performed using a multiplex ‍polymerase chain reaction and the GSTP1 polymorphism was determined by the polymerase chain reaction/restriction ‍fragment length polymorphism (PCR-RFLP) method. The frequencies of GSTM1 and GSTT1 null alleles in normal ‍healthy individuals were observed to be 33.0% and 18.4% respectively. In 7.0% of individuals’ concomitant lack of ‍M1 and T1 genes were observed. For GSTP1, wild (Ile/Ile), heterozygous (Ile/Val) and mutant (Val/Val) genotypes ‍were observed for 44.3%, 50.3% and 5.4% of individuals respectively. The prevalence of the M1 null allele is ‍significantly lower than those documented for English, Turkish, Chinese, Caucasians, Japanese and white (Brazilian ‍and American) populations. However, a significantly higher frequency for T1 null was reported in Chinese and ‍Japanese population. Furthermore, Japanese and African American populations have exhibited significantly higher ‍frequencies of wild and mutant P1 genotypes, respectively, than the Indian population. Thus, our results signify an ‍impact of ethnicity and provide a basis for future epidemiological and clinical studies.     

Genetic Polymorphisms of GSTM1 and GSTT1 Genes in Delhi and Comparison with other Indian and Global Populations

The glutathione S-transferases (GSTs) are involved in the metabolism of many xenobiotics, including an arrayof environmental carcinogens, pollutants, and drugs. Genetic polymorphisms in these genes may lead to interindividualvariation in susceptibility to various diseases. In the present study, GSTM1 and GSTT1 polymorphismswere analysed using a multiplex polymerase chain reaction in 500 normal individuals from Delhi. The frequencyof individuals with GSTM1 and GSTT1 null genotypes were 168 (33.6%) and 62 (12.4%) respectively, and54(10.8%) were having homozygous null genotype for both the genes GSTM1 and GSTT1simultaneously. Thestudied population was compared with reported frequencies from other neighbouring state populations, aswell as with those from other ethnic groups; Europeans, Blacks, and Asians. The prevalence of homozygousnull GSTM1 genotype is significantly higher in Caucasians and Asians as compared to Indian population. Thefrequency of GSTT1 homozygous null genotypes is also significantly higher in blacks and Asians. We believethat due to large number of individuals in this study, our results are reliable estimates of the frequencies of theGSTM1, GSTT1 in Delhi. It would provide a basic database for future clinical and genetic studies pertaining tosusceptibility and inconsistency in the response and/or toxicity to drugs known to be the substrates for GSTs.     

GSTM1 and GSTT1 Genetic Polymorphisms and Breast Cancer Risk in Selected Filipino Cases

Background: The association of genetic polymorphisms with cancer development has been shown to be race- andtumor site-specific. Thus, this study aimed to determine whether polymorphisms in the GSTM1 and GSTT1 genesare associated with breast cancer among selected Filipinos. Methods: A total of 136 histologically confirmed breastcancer cases were age- and sex-matched with 136 clinically healthy controls. Genomic DNA extracted from bloodsamples of participants were screened for GSTM1 and GSTT1 genetic polymorphisms by multiplex PCR. Results:The frequency of null genotypes among the cases (GSTM1: n=78; 57.4%; GSTT1: n=61; 44.9%) was not significantlydifferent (p>0.05) from the controls (GSTM1: n=93; 68.4%; GSTT1: n=59; 43.4%). It was also demonstrated that riskfor breast cancer was increased in passive smokers carrying the GSTM1 null (OR=2.56; 95% CI=1.38-4.75) or GSTT1positive (OR=2.00; 95% CI=1.05-3.83) genotypes. Moreover, risk was decreased in alcohol users carrying the GSTT1null (OR=0.39; 95% CI=0.16-0.97) genotype. Conclusion: This study suggests that variants of GSTM1 and GSTT1may not be risk factors for breast cancer development among Filipinos. However, the risk may be increased when thesegenotypes were combined with lifestyle or environmental factors.     

Modification effects of GSTM1, GSTT1 and CYP2E1 polymorphisms on associations between raw salted food and incomplete intestinal metaplasia in a high-risk area of stomach cancer

Incomplete intestinal metaplasia (IM) is a precursor of stomach cancer. To identify risk factors of incomplete IM, a 2-stage survey was carried out in 1995 among 1,485 residents in Matzu, an area with highest mortality from stomach cancer in Taiwan. There were 312 study subjects including 174 men and 138 women sampled for the gastroendoscopic examination of IM. Information on personal and familial history of stomach cancer, cigarette smoking, alcohol consumption and intake frequency of various salted food items were obtained by personal interview based on a structured questionnaire. Blood samples were collected from each participant. Four biopsies per subject were taken from all subjects at gastroendoscopic examination to diagnose the status of IM pathologically. The Helicobacter pylori in biopsies was detected by the histomorphological or immunochemistry method, and antibodies against H. pylori in serum by the enzyme-linked immunosorbent assay. Plasma level of selenium was determined by atomic absorption spectrometry, plasma level of retinol, alpha-tocopherol, alpha-carotene, and beta-carotene by high performance liquid chromatography, genotypes of glutathione S-transferase (GST) M1 and T1 and cytochrome P450 (CYP) 2E1 by polymerase chain reaction. The significant association between history of stomach cancer among first-degree relatives and incomplete IM was found (odds ratio [OR] = 2.50; 95% confidence interval [CI] = 1.15-5.43). There was no association between H. pylori infection and incomplete IM. Alcohol drinkers for >20 years had an elevated risk compared to non-drinkers (OR = 3.34; 95% CI = 1.19-9.39). No associations between incomplete IM and plasma levels of selenium, retinol, alpha-tocopherol, alpha-carotene and beta-carotene were found. Salted food including salted meat, dehydrated salted vegetables and raw salted seafood consumed at ages of 相似文献   

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

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

Genetic Polymorphisms of Xenobiotic Metabolizing Genes (GSTM1, GSTT1, GSTP1), Gene-Gene Interaction with Association to Lung Cancer Risk in North India; A Case Control Study

Aim: In this case control study involving, 220 human subjects; polymorphisms in xenobiotic metabolizing genes (GST-M1, -T1 and -P1) and their association to lung cancer risk is being analysed among smokers and non-smokers. GSTM1 or GSTT1 gene polymorphism and amino acid changes in GSTP1 have been correlated and may be associated to lung cancer risk. Other factor includes exposure to environmental pollutants and life style choices. We have explored gene-gene and gene-environment interaction in the aetiology of lung cancer risk among north Indian population. Patients and Methods: For the study we have collected 120 lung cancer patient blood samples from Kamala Nehru Memorial Cancer Hospital, Allahabad, Uttar Pradesh and 100 matched controls. DNA was isolated and GST-M1 and - T1 genotyping were assessed by multiplex PCR whereas the GSTP1 polymorphism was analysed using restriction fragment length polymorphism. The risk of lung carcinogenesis was assessed using logistic regression analysis calculating the odd ratio (OR) with 95% confidence interval (CI). Results: The risk of lung carcinogenesis was three fold higher for null GSTT1 (OR=3.045, 95%CI=1.750-5.301, p-value <0.001) genotype; whereas other two types; GSTM1 (OR= 1.342, 95% CI=0.788-2.284, p-value=0.270) and GSTP1 (OR=0.806, 95% CI=0.526-1.236, p-value=0.323) showed no association to lung cancer susceptibility respectively. Smokers diagnosed with lung cancer had more null genotypes for GSTT1 (OR=4.773, 95%CI=1.939-11.751, p<0.001). The ‘at risk’ genotype combination GSTM1 (null) /GSTT1 (null) (OR=1.76, 95%CI; 0.920-3.370, p-value=0.03) showed increased susceptibility to lung cancer risk. The genotype combination of GSTT1 (null)/GSTP1 (Ile/Ile) (p=0.009) was associated with increased lung cancer risk. Conclusion: The results of this study suggest that; GSTT1 null genotype were more susceptible for lung cancer risk and smoking increases the susceptibility for lung cancer several folds among the North Indian population. Gene-gene interaction for null genotypes of GSTM1 and GSTT1 were correlated with higher risk of having lung cancer.     

Glutathione S-transferase M1 and T1 status and the risk of laryngeal cancer: a meta-analysis

Background: Polymorphic variations in GSTM1 and GSTT1 have been implicated as risk factors for various cancers. A number of studies conducted to assess their association with susceptibility to laryngeal carcinomas have yielded inconsistent and inconclusive results. In the present study, the possible association of laryngeal cancer risk with GSTM1 and GSTT1 null genotypes was explored by a meta analysis. Method: A meta-analysis was carried out on case-control studies collected from the literature. The pooled odds ratio (OR) and presence of publication bias in those studies were evaluated. Results: A total of 20 studies concerning laryngeal cancer were identified. The results showed that the pooled OR was 1.22 (95% CI 1.03-1.43) for the GSTM1 polymorphism while for GSTT1 polymorphism, the pooled OR was 1.23 (95% CI 0.96-1.58). No evidence of publication bias was detected among the included studies. Conclusion: The results suggest that the GSTM1 deficiency significantly increases susceptibility to laryngeal cancer whereas GSTT1 null genotype might not be a risk factor.     

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

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

Lack of Associations between Genetic Polymorphisms in GSTM1, GSTT1 and GSTP1 and Pancreatic Cancer Risk: A Multi-Institutional Case-Control Study in Japan

Background: We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizinggenes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. Materialsand Methods: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1,GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilicmolecules. The study population consisted of 360 patients and 400 control subjects, who were recruited fromseveral medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios(ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk.Results: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotypewas approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 andGSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated withthe risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-nullgenotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) forindividuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1-present genotypes. No synergistic effects of smoking or GST genotypes were observed. Conclusions: Our resultsindicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancerrisk in the Japanese subjects in our study.     

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

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

Clinical and pathological implications of GSTM1 and GSTT1 gene deletions in sporadic breast cancer

There is a lack of consensus about the influence of GST M1/T1 gene deletions (DEL) on sporadic breast cancer (SBC). To evaluate the occurrence of DEL in 177 SBC cases and in 169 controls, and compare clinical and biological characteristics. A lower frequency of GSTM1 DEL was observed in mulatto women, OR=0.48 (0.24–0.98). The risk of nuclear grade 3 tumors (GN3) was lower in patients with GSTT1 DEL, OR=0.37 (0.15–0.90). DEL of at least one gene (ALOG) was associated with women who had not breastfed, OR=0.41 (0.19–0.88), and with negative hormone receptor, HR−, ORadj=2.25 (1.03–4.90). Both genes deleted (BGD) was associated with non-classic invasive ductal carcinoma (NCDC), ORadj=12.09 (1.03–142.03). Mulatto women with SBC had a lower frequency of GSTM1 DEL, while tumors differentiated were related to GSTT1 DEL. HR-tumors were related with DEL ALOG, and the BGD was associated with a greater risk of NCDC.     

No Association Between the GSTM1 Null Genotype and Risk of Renal Cell Carcinoma: A Meta-analysis

Background: Many studies have focused on possible associations between the glutathione S-transferase M1 (GSTM1) null genotype and risk of renal cell carcinoma (RCC), but the impact remains unclear owing toobvious inconsistencies among the findings. The present study aimed to quantify the strength of any associationin a meta-analysis. Methods: We searched the PubMed, Embase and CBM databases for studies concerning theassociation between the GSTM1 null genotype and risk of RCC. We estimated the summary odds ratio (OR)with its 95% confidence intervals (95% CI) to assess the association. Results: The meta-analysis showed theGSTM1 null genotype was not associated with risk of RCC overall (OR = 1.04, 95% CI 0.92-1.18, P = 0.501).For Caucasians, the GSTM1 null genotype was also not associated with risk of RCC (OR=1.02, 95% CI 0.90-1.16, P = 0.761). The cumulative meta-analyses showed a trend of no obvious association between GSTM1 nullgenotype and risk of RCC as information accumulated. Sensitivity analyses by omitting those studies also didnot materially alter the overall combined ORs. No evidence of publication bias was observed. Conclusion: Metaanalysesof available data show that the GSTM1 null genotype is not significantly associated with risk of renalcell carcinoma.     

Polymorphism in GSTM1, GSTT1, and GSTP1 and Susceptibility to Lung Cancer in a Japanese Population

Polymorphisms in glutathione S-transferases (GSTs) may predispose to lung cancer through deficient detoxification ‍of carcinogenic or toxic constituents in cigarette smoke, although previous results have been conflicting. Three GST ‍polymorphisms (GSTM1, GSTT1 and GSTP1) were determined among 86 male patients with lung carcinomas and ‍88 healthy male subjects. We found no significant increase in the risk of lung cancer for any genotypes for the nulled ‍GSTM1 [odds ratio (OR)=2.0; 95% confidence interval (95% CI)= 0.8-5.3], the nulled GSTT1 (OR=2.0; 95% CI=0.8- ‍5.1) or the mutated (the presence of a Val-105 allele) GSTP1 (OR=0.96; 95% CI=0.4-5.5). The GST polymorphisms ‍alone may thus not be associated with susceptibility to lung carcinogenesis in male Japanese. However, individuals ‍with a concurrent lack of GSTM1 and GSTT1 had a significantly increased risk (OR=2.7; 95% CI=1.0-7.4) when ‍compared with those having at least one of these genes. No other combinations were associated with lung cancer ‍risk. These results suggest that there may be carcinogenic intermediates in cigarette smoke that are substrates for ‍both GSTM1 and GSTT1 enzymes and that lung cancer risk is increased for individuals who are doubly deleted at ‍GSTM1 and GSTT1 gene loci. Additional large studies are needed to confirm this observation.     

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

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

GSTM1 and GSTT1 Polymorphisms and Susceptibility to Prostate Cancer: A Case-Control Study of the Algerian Population

Objective: Prostate cancer (PCa) is a major public health problem worldwide, with high morbidity and mortality levels. Advanced age, androgen stimulation, and ethnicity have been reported to be possible risk factors. It has been suggested that particular genetic polymorphisms in glutathione S-transferases (GST), xenobiotic-metabolising enzymes, could predispose to prostate cancer through heritable deficiency in detoxification of environmental carcinogens. Conflicts in the published results and the absence of similar in depth studies in Algeria prompted us to perform the present case-control study of GSTM1 and GSTT1 polymorphisms and their possible association with PCa in an Algerian population. Methods: We determined GSTM1 and GSTT1 genotypes for 49 histologically verified prostate cancer patients and in 41 age-matched healthy controls by multiplex polymerase chain reaction (PCR) using peripheral blood DNA samples. Result: While an association between the GSTM1 null genotype and PCa risk (OR= 3.69, 95% CI= 1.30-10.44; P = 0.01) was evident, the GSTT1 null genotype (OR= 0.92, 95% IC= 0.32-2.62; P = 0.49) appeared without influence. Furthermore, no statistically significant differences between the double null genotype and PCa is detected, also no statistically significant differences between smoking status and PCa is detected. Conclusion: The GSTM1 null genotype may increase individual susceptibility to prostate cancer. On the other hand, the null-activity genotype of GSTT1 did not appear to contribute to the risk of prostate cancer in our population.