Frequency Of GSTM1 Null Genotype Research Articles

Glutathione S-transferase polymorphisms and oral cancer: A case-control study in Rio de Janeiro, Brazil

This study evaluates the influence of genetic polymorphisms at GSTM1, GSTT1 and GSTP1 gene loci on oral cancer susceptibility among Brazilians from Rio de Janeiro. DNA extracted from white blood cells of 231 oral cancer patients and 212 hospital controls was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. GSTM1 polymorphism distribution was different between cases and controls (P=0.006), with an overrepresentation of GSTM1 A/B genotype in controls. GSTM1 A/B individuals were at decreased oral cancer risk (OR=0.08; 95% CI=0.05-0.62). No statistically significant association was observed for GSTT1 and GSTP1 polymorphisms. Differences in the GSTM1 and GSTT1 null genotype frequencies were observed between individuals of European origin and African origin, but these genotypes do not seem to influence the risk of oral cancer. Therefore, these results do not support the hypothesis of increased risk of GSTP1 G/G, GSTM1 or GSTT1 null genotypes for developing cancer in oral cavity, but the GSTM1 A/B genotype emerged as a protective factor.

Significance of glutathione S-transferases M1, T1 and P1 polymorphisms in Swedish melanoma patients

Polymorphisms of GSTM1, GSTT1 and GSTP1 were examined in melanoma patients and tumor-free individuals. Relationships between the polymorphisms and tumor characteristics and pigment phenotypes of the patients were analyzed. There was no significant difference in GSTM1 null and GSTT1 null genotypes nor GSTP1 GG genotype between melanoma patients and controls. In melanoma patients, these polymorphisms were not correlated with early or later onset of melanomas or gender of the patients. Frequency of GSTM1 null genotype was higher in patients with melanoma >2.5 mm than in those with tumors <1.0 mm, and higher frequency was found in nodular melanoma than in the other tumor types. GSTP1 GG genotype was more often found in the patients with brown and mixed eye color or brown and black hair than those with blue and green eyes or blond hair. It is unlikely that polymorphisms of GSTM1, GSTT1 and GSTP1 are general risk factors for melanoma in the Swedish population. GSTM1 null genotype was correlated with Breslow thickness and tumor type, which might serve as an additional biomarker for a rapid tumor progression. GSTP1 GG increases risk for melanoma in the subgroup of individuals with dark eyes or hair.

Glutathione S-Transferase M1 and T1 Polymorphisms in Brazilian African Descendants

The glutathione S-transferase gene family has an important role in the biotransformation and detoxification of different xenobiotics and endogenous compounds. Two polymorphic genes of this family, GSTM1 and GSTT1, present null alleles that consequently do not produce the respective enzyme when the genotype is homozygous. These polymorphisms are also interesting for population dynamics studies because they have great frequency variations among different ethnic groups and have been reported worldwide. The distribution of these alleles in urban and Amerindian populations in Brazil has been described, but none of those studies reported on African-descended rural populations. The aim of this study was to analyze the genotype frequency distribution of the GSTM1 and GSTT1 null alleles in an urban sample from the Federal District (n = 91) and in four semi-isolated African-descended populations: Mocambo (n = 55), Rio das Rãs (n = 117), Riacho de Sacutiaba (n = 34), and Kalunga (n = 68). The GSTM1 and GSTT1 null genotype frequencies in these populations range from 17% to 35% for GSTM1 and from 22% to 44% for GSTT1. These values are similar to those described in other African and African-descended populations. Despite this range, there is no distribution difference among the analyzed populations. Combined GSTM1 and GSTT1 null genotype frequencies range from 6% to 13% and are similar to European-derived populations, suggesting admixture with this ethnic group. This can be interpreted as a European contribution to these African-descended populations. Regarding the urban population in the Federal District, our results suggest an important African and European contribution.

GSTT1 and GSTM1 polymorphism in cigarette smokers with head and neck squamous cell carcinoma

SummaryGene variability related to carcinogen activation and detoxification may interfere with susceptibility to head and neck cancer.AimTo investigate the relation between GSTT1 and GSTM1 null polymorphisms and the risk of head and neck squamous cell carcinoma in cigarette smokers.Material and MethodA case-control study conducted at the Sao Jose do Rio Preto Medical School, Brazil. GSTM1 and GSTT1 null genotype frequencies were evaluated by multiplex PCR in 45 cigarette smokers with head and neck squamous cell carcinomas and 45 cigarette smokers without this disease.ResultsThe oral cavity was the most prevalent tumor site for squamous cell carcinoma. The GSTT1 null genotype was found in 33.3% of the Experimental Group and 23.3% of the Control Group (p= 0.311). Experimental and Control Groups had GSTM1 null genotype frequencies of 35% and 48.3% (p=0.582). No association between alcohol consumption and GSTT1 and GSTMI null genotypes was found in these groups (p-values>0.05). There were more men, and alcohol consumption was prevalent in both groups.ConclusionIn this study we were unable to show a correlation between GSTM1 and GSTT1 genotypes and the development of head and neck squamous cell carcinomas in cigarette smokers.

Deletion polymorphism of the GSTM1 gene in lung cancer patients from the Lake District in Turkey

20089 Background: Association of glutathione-S-transferase M1 (GSTM1) polymorphisms and cancer has been demonstrated. Especially the deletion polymorphism of GSTM1 has been related to risk for lung cancer in some studies. We thus investigated the frequency of GSTM1-null genotype in lung cancer patients and healthy individuals from the Lake District in Turkey. Methods: Cases were recruited among patients with clinically and histologically confirmed diagnosis of lung cancer patients from the Lake District. Controls were selected among the nonsmoking healthy blood donors applied to hospital in same region. DNA samples were extracted from whole blood using proteinaz K (20 mg/mL) digestion in lysis buffer (10 mM Tris-HCl, 400 mM NaCl, 2 mM EDTA, % 10 SDS). Homozygous deletion of the GSTM1 gene was determined by PCR using the primers E4F: 5′-CTGCCCTACTTGATTGATGGG-3′, E5R: 5′-CTGGATTGTAGCAGATCATGC-3′, corresponding to exons 4 and 5 of the GSTM1 gene. PCR products were analyzed by 1% agarose gel electrophoresis and UV transilluminator was then used to evaluate the product content. Individuals carrying the GSTM1 gene were identified by the presence of a 273 bp DNA fragment. Results: The study comprised 30 patients and 30 controls. The frequency of GSTM1-null genotype was found to be (n = 14) 46.7% in lung cancer patients and (n = 5) 16.6% in controls. The difference was statistically significant (Fisher’s chi square test: 4.80, P: 0.0251). Conclusion: We found an increased incidence of GSTM1-null genotype among lung cancer patients, indicating that the GSTM1 absence is associated with a slightly increased lung cancer risk in people from the Lake District in Turkey. No significant financial relationships to disclose.

Relationship between genotype and enzyme activity of glutathione S-transferases M1 and P1 in Chinese

Glutathione S-transferases (GSTs) are the major detoxifying Phase II enzyme for eliminating electrophilic compounds. Mutations in GSTM1, GSTP1 and GSTT1 in Caucasian and GSTA1 in Chinese have been found to reduce enzyme activity. However, data on the impact of common genetic polymorphisms of GSTM1 and GSTP1 on enzyme activity in Chinese is lacking. This study aimed to investigate the effect of common GSTP1 and GSTM1 polymorphisms on erythrocyte GST activity in healthy Chinese ( n = 196). GSTM1 null mutation ( GSTM1* 0) was analyzed by a PCR-Multiplex procedure, whereas GSTP1 313A → G polymorphism (resulting in Ile105Val at codon 105) was analyzed by PCR-restriction fragment length polymorphism (RFLP) analysis. Erythrocyte GST activity was measured using 1-chloro-2,4-dinitro-bezene (CDNB) as the model substrate. The frequency of GSTM1 null genotype was 54.3% and the frequency of GSTP1-Ile/Ile, -Ile/Val, and -Val/Val genotype was 60.7%, 35.2% and 4.1%, respectively, with a frequency of 21.7% for the 105 valine allele. Age, gender and smoking did not significantly affect the erythrocyte GST activities. The mean erythrocyte GST enzyme activity for GSTP1*- Ile/ Val genotype group (3.53 ± 0.63 U/g Hb) was significantly lower than that for subjects with GSTP1-Ile/Ile genotype (4.25 ± 1.07 U/g Hb, P = 0.004), while subjects with the GSTP1-Val/Val genotype had the lowest enzyme activity (2.44 ± 0.67 U/g Hb). In addition, the GST activity in carriers of GSTM1* 0/ GSTP1- Ile/ Ile was significantly higher than that of subjects inherited GSTM1* 0/ GSTP1- Ile/ Val or GSTM1* 0/ GSTP1- Val/ Val. However, there is no association between GSTM1 null mutation and reduced enzyme activity. GSTP1 codon 105 mutation led to reduced erythrocyte GST activity in Chinese. A combined GSTP1 and GSTM1 null mutations also resulted in significantly reduced GST activity. Further studies are needed to explore the clinical implications of GSTM1 and GSTP1 polymorphisms.

GSTT1 and M1 polymorphisms in Hürthle thyroid cancer patients

Glutathione S-transferases (GST) are an important part of cell defense against numerous genotoxic compounds and ROS. In order to test the possibility of association between the GSTT1 and M1 null allele variant, and the risk of TCO (thyroid carcinoma with cell oxyphilia), a case-control study was carried out. The rationale for our study was that according to the important roles of GST enzymes in cells and association of GST null genotypes with many types of tumors, inactivating polymorphisms may be genetic susceptibility factors in the etiology of oxyphilic thyroid tumors characterized by mitochondrial dysfunction, increased ROS production and resistance to chemio- and radio-therapy. We found the frequency of GSTT1 null genotype of 19.2% in cases and 15.7% in controls, with an adjusted odds ratio (OR) of 1.4 (95% confidence interval (CI), 0.70–2.81), and a frequency of GSTM1 null genotype of 59% in cases with oxyphilic tumors and of 55.6% in controls (OR 1.24; 95% CI, 0.62–2.48), indicating that the GSTT1 and M1 null genotypes do not increase the risk of development of oxyphilic tumors.

Glutathione S-transferase M1 and T1 Gene Deletion Associated with Increased Susceptibility to Nasopharyngeal Carcinoma

Objective: To evaluate the association of Glutathione S-transferase (GST) M1 and T1 genetic polymorphisms and susceptibility to nasopharyngeal carcinoma (NPC) in a high risk area of Guangxi Zhuang Autonomous Region (province), Southwest of China. Methods: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (GSTM1 and GSTT1 null genotypes). A total of 127 NPC cases and 207 controls were recruited. Results: GSTM1 and GSTT1 null genotype frequencies were higher among NPC patients at a level of statistical significance (P<0.005; P<0.001 respectively), and both GSTM1 and GSTT1 null genotype were even more significant (P<0.001). Conclusion: NPC is the most common cancer in Guangxi. GST enzymes are involved in the detoxification of many environmental carcinogens. Homozygous deletions of GSTM1 and GSTT1 have been associated with several types of cancer. The risk to develop NPC has been associated with environmental factors such as cigarette smoking and EB virus infection. The present results indicate that the GSTM1 and GSTT1 deletion polymorphisms are associated with an increase risk of susceptibility to NPC, and both detoxific enzyme genes deletion is more important than a single gene deletion for the susceptibility to NPC.

A comparison of glutathione S-transferase mutant frequencies in healthy Han and Uygur Chinese

This study was to compare the frequencies of genetic polymorphisms of GSTM1, GSTT1, and GSTP1 in Uygur Chinese with those in Han Chinese. GSTM1 and GSTT1 polymorphisms were analyzed by a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. The frequency of GSTM1 null genotype in Han Chinese (56.1%) was similar to that in Uygur Chinese (53.2%) (P = 0.592), whilst the frequency of GSTT1 null genotype in Han Chinese (50.0%) was significantly (P < 0.05) higher than that of Uygur Chinese (26.6%). GSTP1 had a genotype distribution of 60.7% I/I, 35.2% I/V and 4.1% V/V in Han Chinese, and 51.3% I/I, 40.2% I/V and 8.4% V/V in Uygur Chinese. There is marked ethnic difference in the mutant frequencies of GSTT1 and GSTP1, but not GSTM1, between Uygur and Han Chinese.

Relationship between GSTT1, GSTM1 and NQO1 gene polymorphism and acute myeloid leukemia and recurrent chromosome translocations

To investigate the impact of GSTM1, GSTT1 and NQO1 genotypes on susceptibility to acute myeloid leukemia (AML) and recurrent chromosome translocations of AML. GSTT1, GSTM1 and NQO1 genotypes were detected in 228 adult patients with de novo AML and 241 controls by PCR or PCR-RFLP. The frequency of GSTM1 null genotype in the AML patients was 62.3%, significantly higher than that in the normal controls (52.7%, P = 0.036), however, no significant difference was found in the incidence of GSTT1 null genotype. The frequencies of NQO1(C609T) C/T and T/T genotypes were 53.1% and 25.0% respectively among the total AML patients (53.1% and 25.0% respectively), 64.3% and 25.0% respectively among the AML patients with t (8; 21) (q22; q22)/AML-ETO fusion gene, and 57.1% and 26.0% respectively among the AML patient with t (15; 17) (q22; q11)/PML-RARalpha fusion gene, all significantly higher than those in the controls (49.4% and 13.7% respectively). The relative risk of t (8; 21) (q22; q22)/AML-ETO (+) AML was 4.487 (95% CI: 1.282-15.705) for the subjects with NQO1(C609T) C/T genotype, and was 6.293 (95% CI: 1.536-25.782) for the subjects with NQO1(C609T) T/T genotype. The relative risk of t (15; 17) (q22; q11)/PML-RARalpha (+) AML was 2.531 (95% CI: 1.286-4.981) for the subjects with NQO1(C609T) C/T genotype, and was 4.149 (95% CI: 1.856-9.275) for the subjects with NQO1(C609T) T/T genotype. Determination of the NQO1(C609T) genotypes may be used as a stratification marker to predict high-risk individuals for AML, especially for AML with t (8; 21) (q22; q22)/AML-ETO fusion gene and t (15; 17) (q22; q11)/PML-RARalpha fusion gene.

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).

Association of genetic polymorphisms in glutathione S-transferases M1 with hepatitis beta-related hepatocellular carcinoma

To investigate the association of genetic polymorphisms in glutathione S-transferases(GST) M1 with hepatitis beta-related hepatocellular carcinoma (HCC). Genomic DNA was isolated from peripheral blood of HBsAg carriers, including 91 cases of HCC, 58 liver cirrhosis(LC), 63 chronic hepatitis B(CHB), and 134 normal controls. GSTM1 genotypes were detected by multiplex PCR. The null genotype of GSTM1 was significantly frequent in patients with HCC compared with controls (P<0.05), but there were no significant differences in frequency of GSTM1 null genotype among patients with liver cirrhosis, chronic hepatitis B and normal controls. Subjects carrying null genotypes of GSTM1 had higher risk of developing HCC compared with those carrying positive genotype (OR=1.81.95% CI=1.05 approximately equals 3.12). The GSTM1-null genotype may be associated with an increased risk of HCC, but not of CHB and LC.

Study on the association between genetic polymorphism of CYP2E1, GSTM1 and susceptibility of lung cancer

Lung cancer is the leading cause of malignant tumor death among Chinese population. It has been known that the development of lung cancer may be associated with genetic po-lymorphism of some lung cancer related genes. The aim of this study is to evaluate the relationship between genetic polymorphism of metabolizing enzymes and susceptibility of lung cancer in Chinese population. Polymorphism of CYP2E1 RsaI/PstI and GSTM1 was detected in 99 patients with lung cancer and 66 patients with benign pulmonary disease by PCR-RFLP and PCR. The association between genetic polymorphism and susceptibility of lung cancer was analyzed. No significant difference in three RsaI/PstI genotype distribution of CYP2E1 was found between lung cancer group and control group (Chi-Square=1.374, P=0.241). (2) The frequency of GSTM1-null genotype in lung cancer group was significantly higher than that in control group (57.6% vs 40.9%, Chi-Square=4.401, P=0.036). (3) The individuals who carried with GSTM1-null genotype had a 1.96 fold increased risk of lung cancer (OR=1.96, 95%CI=1.042-3.689, P=0.037) than those who carried with GSTM1-present genotype. (4) When data were stratified by smoking status, the smokers who carried with c1/c1 genotype had a significantly higher risk of lung cancer (OR=3.525, 95%CI=1.168- 10.638, P=0.025) than those never-smokers who carried with at least one c2 allel. (5) When combination of polymorphism of CYP2E1 RsaI/PstI genotype and GSTM1 genotype was analyzed, compared with individuals who had concurrent present of GSTM1 and at least one c2 allel genotype, the risk of lung cancer for combination of GSTM1 null and c1/c1 genotype was increased significantly (OR=3.449, 95%CI=1.001- 11.886, P=0.050). Considering smoking status, compared with never-smokers who had concurrent present of GSTM1 and at least one c2 allel genotype, the risk of lung cancer for combination of GSTM1 null and c1/c1 genotype was remarkably increased (OR=11.553, 95%CI=1.068-124.944, P=0.044), as well as that for combination of GSTM1 null and at least one c2 allel genotype (OR=13.374, 95%CI=1.258-142.166, P= 0.032). (1)GSTM1 null genotype is an important factor associated with increased risk of lung cancer. (2) The combination of c1/c1 and GSTM1-null genotype can remarkably increase risk of lung cancer both in smokers and non-smokers.

GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high‐risk italian population

Glutathione S-Transferases (GSTs) are a family of phase II enzymes involved in the detoxification of potential carcinogens and provided of a strong antioxidant function by neutralizing electrophiles and free radicals. The GSTM1 and GSTT1 isoenzymes exhibit deletion polymorphisms, resulting in a lack of activity, and the null genotypes have been associated with increased cancer risk at several sites, including the stomach, although with contrasting results. We carried out a case-control study to evaluate whether these polymorphisms modulate the risk of developing gastric cancer (GC). Genotypes for GSTM1 and GSTT1 were obtained from a series of 175 histologically confirmed GC patients and a large series of 546 healthy controls randomly sampled from the general population of Tuscany, an area at high GC risk. No difference in the frequency of GSTM1 null genotype was observed between cases and controls, whereas the GSTT1 null genotype was more frequent among cases (p = 0.04). Multivariate single-gene analyses adjusted for possible confounders showed that the GSTT1 null genotype, but not the GSTM1 null genotype, was associated with an increased GC risk. Combined-genotype analyses showed a significantly increased GC risk only for the double null (GSTM1-GSTT1) genotype (OR = 2.27; 95% CI: 1.14-4.53). A statistically significant positive interaction between the 2 null genotypes was observed (p = 0.02). Our findings suggest that only subjects lacking both GSTM1 and GSTT1 activity are at increased GC risk. This study provides further support to the hypothesis that the risk of developing GC is influenced by inter-individual variation in both carcinogen detoxification and antioxidant capacity. (c) 2005 Wiley-Liss, Inc.

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

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

Biomarcadores de suscetibilidade à endometriose

OBJECTIVE: to determine GSTT1 and GSTM1 null genotype frequencies as well as CYP1A1 polymorphic allele frequencies in a group of women with endometriosis, and to compare these frequencies with those observed in a group without endometriosis (control), aiming at a possible identification of biomarkers of susceptibility to endometriosis. METHODS: a total of 50 women with suggestive clinical signs of endometriosis underwent videolaparoscopy and biopsies were evaluated histologically. Endometriosis was present in 25 women (case group). Negative results were found in 25 women (control group). GSTT1 and GSTM1 null genotypes were assessed by multiplex polymerase chain reaction (PCR). The investigation of the polymorphic allele of the gene CYP1A1 was performed by PCR-RFLP (restriction fragment length polymorphism). For statistical analysis, the Fisher exact test was used. RESULTS: in both groups, the deletion polymorphism frequencies presented values of 16% for the gene GSTT1 and of 44% for the gene GSTM1; therefore, the results did not show differences in the distribution of the GSTT1 and GSTM1 null genotypes among the studied groups. The allelic frequency for the m1 allele of the gene CYP1A1 was higher in the women with endometriosis (0.22), although not statistically significant, when compared to the control group (0.14). CONCLUSION: the results did not show an association between the evaluated polymorphisms and the endometriosis diagnosis.

Glutathione S-transferase T1 and M1 polymorphisms and risk of thyroid neoplasms

Background: In order to test the possibility of association between GSTT1 and M1 (glutathione S-transferase) null allele variant, in which the entire gene is absent, and the risk of TCO (thyroid carcinoma with cell oxyphilia), the case-control study was carried out. Methods: Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR in the DNA from 108 healthy individuals and in DNA from samples of thyroid tumors from 130 patients of the same race and origin as the control group (Caucasian, Italian). The following types of NMTC were analyzed: oxyphilic adenoma (OA), oxyphilic carcinoma (OC) papillary thyroid carcinoma with oxyphilic features (PTCof), follicular adenoma (FA), follicular carcinoma (FC), follicular variant of PTC (fvPTC) and classical PTC. Associations between prevalence of particular genotypes and the occurrence of TCO (versus controls) and other subtypes of NMTC were tested. Associations were quantified by calculating OR (odds ratio) with 95% confidence interval. StatGraphics Plus v. 5 software (Manugistics) was used for statistical analysis. Results: In this study of the association between the GSTT1 and M1 null genotype and the increased risk of TCO, the frequency of GSTT1 null genotype of 19.2% in cases and 15.7% in controls was found with an adjusted odds ratio (OR) of 1.4 (95% confidence interval (CI) 0.70-2.81), and the frequency of GSTM1 null genotype of 59% in cases with oxyphilic tumors and of 55.6% in controls (OR 1.24; 95% CI, 0.62-2.48). Conclusion: These results indicate that the GSTT1 and M1 null genotypes do not increase the risk of development of oxyphilic tumors, as well as other types of NMTC that have been included in this study.

Study of the deletion mutation of glutathione transferase M1 gene and its role in susceptibility to hepatocellular carcinoma

Objection: To investigate the glutathione S transferase Ml (GSTM1) gene inherent deletion and its relation to prevalence of hepatocellular carcinoma (HCC) in Guangxi, China. Methods: The GSTM1 gene polymorphism of 120 HCC patients and 100 healthy subjects both from the same high aflatoxin B1 (AFB1) contaminated area were detected using PCR technique with special primers. Another 40 patients from AFB1 low risk area were also tested. Results: In HCC high risk area, it was found that the frequencies of GSTM1 null genotype in HCC patients and healthy subjects were 59% and 51% respectively, with no significant difference. However, the frequency of GSTMl-null genotype in control group from AFB1 low risk area was lower than those from high risk area (P<0.01). Conclusion: Populations in this HCC endemic region show a higher rate of GSTMl-null genotype, which may be partially responsible for the susceptibility to AFB1 induced HCC. But the detoxification effect of GSTM1 alone is not sufficient to resist the genetic toxicity of AFB1, especially in those people who expose to excess AFB1. The GSTM1 gene deletion would not be suitable as an independent predictor of susceptibility to HCC.

易感基因CYP2E1、GSTM1、GSTT1基因多形性在台灣原住民、泰國及菲律賓等種族間分佈差異之研究

Background. Individuals metabolize chemical substrates or drugs with different the susceptibility; the differences are especially noticeable among individuals who originate from different ethic groups. Several studies have shown that the different susceptibilities could be determined using genetic polymorphisms of the enzymes which metabolized the substrate(s) or chemical(s). The polymorphisms of individuals to some cancers, in our study, we focused on the differences of these three genes in Taiwan aborigines, Thai and Fillipino populations. Method. The study population included members of various tribes of aboriginal people including the Pancah, Ayayal, Bunun, Paiwan, Puyumar, Min-nan, and natives of Thailand, and the Philippines. DNA was isolated from peripheral leukaocytes. The target DNA fragments were amplified using polymerase chain reaction, and genotype were determined using restriction fragment length polymorphism. Results. The frequency of c2 allele in members of the Pancah was 19.4%, of the Ayayal was 43.4%, of the Bununis was 29.6%, of the Paiwan was 36%, of the Puyumar was 22%, of the Min-nan was 19.6%, of the Thai was 16%, and of the Filipinos was 13.6%. The frequency of GSTM1null genotype was 56% in members of the Min-nan, 63% of the Pancah, 53% of the Ayayal, 53% of the Bunun, 42.5% of the Paiwan, 46% of the Puyumar, 48% of the Thai, and 53% of the Filipinos. The GSTT1 null genotype frequency was 44% in the members of the Min-nan, 35% of the Pancah, 52%of the Ayayal, 25% of the Bunun, 40% of the Paiwan, 41% of the Puyumar, 23% of the Thai, and 41% of the Filipinos. Conclusions. The CYP2E1-Rsal polymorphisms vary among different ethnic groups. The frequency of GSTT1 null genotype in members of the Puyumar and Thai populations were significantly lower than that of the Min-nan. The GSTM1 polymorphism was not significantly different among the populations in this study.

Genetic polymorphisms of CYP2D6, CYP1A1, GSTM1 and p53 genes in a unique Siberian population of Tundra Nentsi.

The purpose of this study was to establish the frequencies of CYP2D6, CYP1A1, GSTM1 and p53 polymorphic genotypes in Tundra Nentsi, which comprises the small group of indigenous people belonging to Northern Mongoloids and Caucasians of Western Siberia. A total number of 102 Tundra Nentsi individuals and 96 Caucasians of Western Siberia were genotyped by means of polymerase chain reaction-based assays. Mutated alleles comprising CYP2D6*4, CYP1A1Val, GSTM1*0 and p53Pro were analysed along with the wild-type alleles. The results showed the intermedial position of CYP2D6*4 allele frequency in Tundra Nentsi, compared to Caucasians and Orientals (0.07 versus 0.2, P = 0.0003; 0.07 versus 0.003, P = 1 x 10(-6), respectively). Thus, our data indicate that the intermedial position of Tundra Nentsi between Orientals and Caucasians most likely shows the Caucasian ancestral origin of CYP2D6*4 allele. Comparative analysis of p53Pro allele frequency showed the pronounced ethnic differences with geographic gradient. Though the frequency of p53Pro allele ranged from 0.17 in Tundra Nentsi up to 0.3 in Caucasians of Western Siberia (P = 0.002), which is in agreement with the previously reported radial distribution of the known genetic markers. No differences were found in the CYP1A1Val allele distribution among Caucasians of Western Siberia and Caucasoid populations presented in other studies, whereas the frequency of Val allele in Nentsi was 1.5-fold higher (P = 0.076) compared to the Japanese group. It was found that the frequency of GSTM1 null genotype in Tundra Nentsi was only 39.8%. The frequency of GSTM1 null genotype in females was higher than in males (0.27 and 0.50, respectively) but that difference was not statistically significant. Comparative analyses of the distribution of putative markers towards cancer susceptibility, CYP1A1Val, GSTM1*0 and p53Pro alleles, have shown that the healthy Tundra Nentsi population (Northern Mongoloids) have a low number of p53Pro alleles and GSTM1*0/*0 genotypes and a high level of CYP1A1Val alleles. Further investigations of gene polymorphisms in isolated Northern native populations would be valuable in clarifying the origin of Northern natives. All this is important for comparative analyses of pharmacogenetic data in Mongoloid populations.