Glutathione S-transferase P1 Gene Polymorphism Research Articles

Association of Glutathione S-Transferase P1 (GSTP1) Gene Polymorphism with the Response to Platinum Based Chemotherapy in Patients with Non-Small Cell Lung Cancer

Abstract Background Lung cancer is one of the most commonly diagnosed cancers and despite therapeutic advances, mortality remains high. Platinum based chemotherapy remains the mainstay of adjuvant or first line chemotherapy in non small cell lung cancer (NSCLC) treatment, pathophysiological features along with genetic background significantly influence therapeutic efficacy of platinum-based chemotherapy. GSTP1 gene is a member of the cytosolic superfamily of glutathione-S-transferases, which is responsible for phase II detoxification enzymes that convert various reactive metabolites to more water-soluble and less harmful forms by conjugating them with glutathione. The genetic polymorphism GSTP1 rs1695 is associated with decreased substrate specific catalytic activity and the reduced enzyme activity which may reduces platinum detoxification, thus promoting better response rates to platinum-based chemotherapy. Aim of the Work In the present study was aimed to investigate the association of GSTP1 gene polymorphism with the response to platinum based chemotherapy in patients with NSCLC in order to prevent the non necessary exposure to the toxic effect of chemotherapy. Patients and Methods The study was a retrospective cross sectional study conducted on 50 NSCLC patients who were recruited from the Oncology clinic in Ain Shams University Hospitals, twenty of them were responders to platinum based chemotherapy and the other 30 were not responders according to RECIST criteria. All subjects underwent full medical history focusing on tobacco smoking and family history of cancers, thorough clinical examination, histological diagnosis of NSCLC and TNM classification, radiological studies: computed tomography of chest and abdomen and laboratory investigations in the form of: complete blood picture (CBC), liver function tests and kidney function tests. Detection of the GSTP1 rs1695 (A/G) polymorphism by real-time PCR was done for both the responders and the non responders group. Results There was no statistically significant difference between the responders’ and non responders’ groups regarding the genotypic distribution (p > 0.05). However, the G allele was significantly higher in the responders’ group compared to the non responders’ group with p value < 0.05. Conclusion The present study did not confirm the presence of significant association between the genotypic frequencies of the GSTP1 rs 1695 among the responders and the non responders group, but despite that it showed that the A allele was significantly higher in the non responders’ group compared to the responders’ group. However, the G allele was significantly higher in the responders’ group compared to the non responders’ group. Further studies with higher sample size are needed to clarify the association.

Association of GSTP1 and PLCE1 gene polymorphisms with primary esophageal cancer

To assess the association of polymorphisms of glutathione S-transferase P1 (GSTP1) and phospholipase C epsilon-1 (PLCE1) genes with the susceptibility of primary esophageal cancer and their interaction with environmental factors. 162 patients with primary esophageal cancer and 162 healthy controls were recruited in this cross-sectional study. Basic information such as gender, age, history of smoking and alcohol consumption and family history of esophageal cancer were collected. Single nucleotide polymorphisms at A105G locus of GSTP1 gene and rs3765524, rs2274223 and rs3781264 loci of PLCE1 gene were detected. A logistic regression model was established to analyze the risk factors of esophageal cancer and the interaction among the factors. The proportions of individuals with smoking history, family history of esophageal cancer and hot diet in esophageal cancer group were higher than those in the control group (P<0.05). Conditional Logistic regression analysis showed that smoking, family history of esophageal cancer and GG genotype at the rs2274223 locus of PLCE1 gene were the risk factors for esophageal cancer (P<0.05), and AG/GG genotypes at the A105G locus of GSTP1 gene were the protective factors for esophageal cancer (P<0.05). In the two-factor interaction model, both AA genotype at A105G locus of GSTP1 gene and GG genotype at rs2274223 locus of PLCE1 gene had an interaction with smoking, and the risk of esophageal cancer has increased by 83.6% and 85.7%, respectively (P<0.05). AA genotype at A105G locus of GSTP1 gene, GG genotype at rs2274223 locus of PLCE1 gene and smoking constituted the best three-factor interaction model, and the risk of esophageal cancer has increased by 244.0% (P<0.05). Four-factor interaction model analysis showed that the risk of esophageal cancer among individuals with AA genotype at A105G locus of GSTP1 gene, GG genotype at rs2274223 locus of PLCE1 gene, smoking and family history of esophageal cancer has increased by 264.4% (P<0.05). The AG and GG genotypes at the A105G locus of GSTP1 gene are protective factors for esophageal cancer, and the GG genotype at rs2274223 locus of PLCE1 gene is a risk factor, both of them may interact with smoking and affect the susceptibility to esophageal cancer.

Potential role of glutathione S-transferase P1 gene polymorphism and metabolic syndrome in lower urinary tract symptoms attributed to benign prostatic hyperplasia.

The aim of the study is to investigate the effects of glutathione S-transferase P1 (GSTP1) gene polymorphism and metabolic syndrome (MS) on lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia (BPH). This study included 195 patients diagnosed with LUTS secondary to BPH as case group, divided into simple BPH group (S-BPH group) and combined with MS group (MS-BPH group). Control group included 200 healthy elderly men without LUTS. Use peripheral blood samples detected the GSTP1 gene polymorphism (Ile 105 Val A → G polymorphism) by polymerase chain reaction-restriction fragment length polymorphism. Recorded age, GSTP1 gene polymorphism, international prostate symptom score (IPSS), prostate volume (PV), residual urine volume (RV), maximal urinary flowrate (Qmax), and prostate-specific antigen (PSA) to statistical analysis. Pairwise compared between control group, S-BPH group and MS-BPH, the PV (P < 0.001), PSA (P < 0.001), RV (P < 0.001), Qmax (P < 0.001), IPSS (P < 0.001), frequencies of GSTP1 gene (P < 0.05) were shown significant different, and MS-BPH group had larger PV, and more severe LUTS. In case group, variation genotypes (GSTP1 A/G + G/G) always had larger PV, higher PSA and IPSS, more RV and lower Qmax than homozygote (GSTP1 A/A) and the comparison were significant different (P < 0.05). Variation genotypes were positively correlated with PV (β = 0.092, P < 0.001), RV (β = 0.228, P = 0.004), IPSS (β = 0.274, P = 0.038), PSA (β = 1.243, P < 0.001) and negatively correlated with Qmax (β = -0.362, P = 0.025). In patients with BPH, GSTP1 variation genotypes and MS might be potential risk factors for faster progression of benign prostatic enlargement and LUTS, which might increase the surgical rate. ChiCTR-IPR-14005580.

An updated meta-analysis for association of glutathione S-transferase P1 gene polymorphism with the susceptibility of lung cancer.

The conclusions on the association between glutathione S-transferase P1 (GSTP1) gene polymorphism and lung cancer risk are still debated. This meta-analysis was performed to update the association between GSTP1 and the risk of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Fifty reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and lung cancer susceptibility. The association between GSTPI G allele/GG genotype and lung cancer risk was found in this meta-analysis (G allele: odds ratio [OR] = 1.08, 95% confidence interval [CI]: 1.02-1.14, P = 0.006; GG genotype: OR = 1.09, 95% CI: 1.00-1.18, P = 0.04). However, the AA genotype was not associated with the susceptibility of lung cancer. GSTP1 G allele/GG genotype is associated with the lung cancer susceptibility.

Glutathione S-transferase P1 gene polymorphisms and susceptibility to coronary artery disease in a subgroup of north Indian population.

The present study aimed to investigate the association of g.313A>G and g.341C>T polymorphisms of GSTP1 with coronary artery disease (CAD) in a subgroup of north Indian population. In the present case-control study, CAD patients (n = 200) and age-matched, sex-matched and ethnicity-matched healthy controls (n = 200) were genotyped for polymorphisms in GSTP1 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotype distribution of g.313A>Gand g.341C>T polymorphisms of GSTP1 gene was significantly different between cases and controls (P = 0.005 and 0.024, respectively). Binary logistic regression analysis showed significant association of A/G (odds ratio (OR): 1.6, 95% CI: 1.08-2.49, P = 0.020) and G/G (OR: 3.1, 95% CI: 1.41-6.71, P = 0.005) genotypes of GSTP1 g.313A>G, and C/T (OR: 5.8, 95% CI: 1.26-26.34, P = 0.024) genotype of GSTP1 g.341C>T with CAD. The A/G and G/G genotypes of g.313A>G and C/T genotype of g.341C>T conferred 6.5-fold increased risk for CAD (OR: 6.5, 95% CI: 1.37-31.27, P = 0.018).Moreover, the recessive model of GSTP1 g.313A>G is the best fit inheritance model to predict the susceptible gene effect (OR: 2.3, 95% CI: 1.11-4.92, P = 0.020). In conclusion, statistically significant associations of GSTP1 g.313A>G (A/G, G/G) and g.341C>T (C/T) genotypes with CAD were observed.

Role of glutathione S-transferase P-1 (GSTP-1) gene polymorphism in COPD patients

BackgroundCOPD is a multifactorial disease. It is a widely distributed disease with high morbidity and mortality, associated with different pathologies. The link between glutathione S-transferase P-1 (GSTP1) polymorphism and COPD needs to be clarified. ObjectivesTo show the relationship between GSTP1 gene polymorphism and pathogenesis of COPD, and to clarify the role of smoking in GSTP1 gene polymorphism. Patients and methodsThis study carried out on 30 COPD patients met the clinical criteria of COPD set by GOLD 2013 and 20 healthy controls. Blood was sampled for studying GSTP1 gene polymorphism by PCR-RFLP. ResultsThere was a significant difference between group A (COPD smokers) and group B (COPD non smokers) regarding the presence of non mutant and heterozygous mutation. GSTP1 mutation was significantly higher in group C (smoking controls) than group D (non smoking controls). There was a highly significant difference between smoking subjects than non smoking compared with mutation. There was no significant difference in mutation between smokers and ex-smokers. There was no significant difference between studied subjects having heterozygous mutation and subjects without as regards their spirometry results. ConclusionThere is a significant association between GSTP1 gene polymorphism and the development of COPD, and smoking have a role in GSTP1 gene polymorphism. The polymorphism has no relation to disease severity.

Genetic Polymorphisms of Cytochrome P4501A1 (CYP1A1) and Glutathione S-Transferase P1 (GSTP1) and Risk of Hepatocellular Carcinoma Among Chronic Hepatitis C Patients in Egypt.

Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase P1 (GSTP1) genes are involved in the metabolism of many carcinogens. Polymorphisms in these genes with altered enzyme activity have been reported. The present study evaluated the synergistic effect between CYP1A1 and GSTP1 gene polymorphisms and smoking on development of HCV-related liver disease and hepatocellular carcinoma (HCC). The patients group comprised 40 patients with HCC and 40 patients with liver cirrhosis. The control group comprised 40 healthy subjects having no history of malignancy. The genetic polymorphisms were studied using polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) technique on blood samples. The number of current or former smoker among HCC and cirrhotic patients as well as the median Pack/year of cigarette smoked were significantly higher in HCC and liver cirrhotic patients than in control group. Subjects with CYP1A1 gene variants (m1 and m3) had no significant risk to develop cirrhosis or HCC compared to control group. Individuals carrying the Ile/Val genotype of GSTP1 had a significant increased risk of HCC (OR of 2.2, 95% CI 1.143-4.261) and had larger tumor size. No significant risk was observed on combining both genes variants or on combining smoking with variants of both genes. In conclusion, the GSTP1 Ile/Val genotype and Val allele are associated with an increased risk of HCC. CYP1A1 and GSTP1 genes variants interaction did not increase the risk of HCC.

Investigation of TNF-alpha gene (G308A) and GSTP1 gene (Ilel05Val) polymorphisms in Turkish patients with retinopathy of prematurity.

Retinopathy of prematurity (ROP) is one of the most frequent causes of blindness in newborn babies. Currently, its etiology is not fully understood.-In this study we aimed to investigate the correlation between a patient group with ROP and a control group in terms of the tumor necrosis factor-alpha (TNF-alpha) (G308A) gene and glutathione-S-transferase P1 (GSTP1) (Ilel05Val) gene polymorphism. Sixty-two patients diagnosed with ROP and 58 control subjects were included in this study. For TNF-alpha (G308A) gene and GSTP1 (Ilel05Val) gene polymorphisms, the polymerase chain reaction-restriction fragment length polymorphism method was used. In statistical analysis the significance level was determined as P < 0.05. When the patient and control groups were compared in terms of TNF-alpha (G308A) gene and GSTP1 (Ilel05Val) gene polymorphisms, no statistically significant difference was found (P > 0.05). In our study, no correlation was identified between TNF-alpha (G308A) gene and GSTP1 (Ilel05Val) gene polymorphisms and susceptibility for development of ROP. Further studies are required with more cases of ROP patients and other gene polymorphisms that could be related.

Association of glutathione S-transferase P1 gene polymorphism with the risk of small-cell carcinoma of lung cancer

The conclusions of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the risk of small-cell carcinoma of lung cancer are still debated. GSTP1 is one of the important mutant sites reported at present. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of small-cell carcinoma of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Ten reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and small-cell carcinoma of lung cancer. The G allele and GG genotype were not associated with the susceptibility of risk of small-cell carcinoma in overall populations, East-Asians and Turkish population. However, there was an association between GG genotype with the risk of small-cell carcinoma in Caucasians. In conclusion, GG genotype was associated with the risk of small-cell carcinoma in Caucasian patients with lung cancer. However, GSTP1 A/G gene polymorphism is not associated with the susceptibility of small-cell carcinoma in overall populations, East-Asians and Turkish population.

Association of Glutathione S-Transferase P1 (GSTP1) Polymorphism with Tourette Syndrome in Taiwanese Patients

The etiology of Tourette syndrome (TS) is multifactorial. TS vulnerability may be associated with genetic and environmental factors. From the genetic point of view, TS is heterogeneous. Previous studies showed that some single-nucleotide polymorphisms (SNPs) of the glutathione-S-transferase P1 (GSTP1) gene can affect cellular proliferation and apoptotic activity and TS is a neurodevelopmental disorder. We guessed that there was a relationship between TS and genetic variants of the GSTP1 gene. Therefore, in this study, we aimed to test the hypothesis that GSTP1 SNPs were associated with TS. We performed a case-control study. One hundred twenty-one TS children and 105 normal children were included in the study. Polymerase chain reaction was used to identify the GSTP1 gene polymorphism at position rs6591256 (A/G, promoter polymorphism) in TS patients and normal children. The polymorphism at position rs6591256 in the GSTP1 gene revealed significant differences in the allele (p=0.0135) and genotype (p=0.0159) distributions between the TS patients and the control group. The A allele was present at a higher frequency than the G allele in the TS patients compared with the control group (odds ratio [OR]=1.91, 95% confidence interval [CI]: 1.14-3.21). The AA genotype was associated with susceptibility to TS with an OR of 2.38 for the AA versus AG genotype (95% CI: 1.29-4.41). These findings suggest that variants in the GSTP1 gene may play a role in susceptibility to TS.

A meta-analysis of the association between glutathione S-transferase P1 gene polymorphism and the risk of adenocarcinomas of lung cancer

Results of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the adenocarcinomas of lung cancer are still debated. This meta-analysis was performed to evaluate the association between GSTP1 A/G gene polymorphism and the risk of adenocarcinomas of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. 16 reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and the risk of adenocarcinomas of lung cancer. The G allele and GG genotype were not associated with the susceptibility of risk of adenocarcinomas. Furthermore, in the sensitivity analysis, the results were similar with those from the non-sensitivity analysis. GSTP1 G allele or GG genotype is not a biomarker to be associated with the susceptibility of adenocarcinomas of lung cancer.

A meta-analysis of the association of glutathione S-transferase P1 gene polymorphism with the susceptibility of breast cancer

Glutathione S-transferase P1 (GSTP1) is one of the important mutant sites for the cancer risk at present. The conclusions of the published reports on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer are still debated. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of breast cancer. The association reports were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. 35 investigations were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and breast cancer susceptibility, consisting of 40,347 subjects (18,665 patients with breast cancer and 21,682 controls). The association between GSTP1 A/G gene polymorphism and breast cancer risk was not found for overall population, Caucasians and Africans. Interestingly, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer in Asians (G allele: OR = 1.10, 95 % CI: 1.04-1.17, P = 0.001; GG genotype: OR = 1.36, 95 % CI: 1.14-1.62, P = 0.0008; AA genotype: OR = 0.92, 95 % CI: 0.85-0.98, P = 0.02). Furthermore, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer for the analysis of the controls from hospital. In conclusion, GSTP1 A/G gene polymorphism is associated with the breast cancer susceptibility in Asians. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer should be performed in further.

Association of glutathione S-transferase P1 gene polymorphism with the histological types of lung cancer: a meta-analysis

The conclusions of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) A/G gene polymorphism and the histological types of lung cancer are still debated. GSTP1 is one of the important mutant sites reported at present. This meta-analysis was performed to evaluate the association between GSTP1 and histological types of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Seventeen reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and histological types of lung cancer. The G allele and GG genotype were not associated with the susceptibility of risk of squamous cell carcinomas, adenocarcinomas, small cell carcinoma, non-small cell carcinoma or large cell carcinoma. However, in the sub-group analysis, there was an association between G allele/GG genotype with the risk of squamous cell carcinomas in East-Asians and GG genotype was associated with the risk of small cell carcinoma in Caucasians. In conclusion, GSTP1 A/G gene polymorphism is not associated with the susceptibility of squamous cell carcinomas, adenocarcinomas, small cell carcinoma, non-small cell carcinoma or large cell carcinoma.

Association of glutathione S-transferase P1 gene polymorphism with the susceptibility of lung cancer

The conclusions of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the risk of lung cancer are still debated. GSTP1 is one of the important mutant sites reported at present. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Forty-four reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and lung cancer susceptibility, consisting of 12,363 patients with lung cancer and 13,948 controls. The association between GSTPI G allele and lung cancer risk was found in this meta-analysis (OR 1.08, 95 % CI 1.02-1.15, P = 0.01). However, the GG genotype and AA genotype were not associated with the susceptibility of lung cancer. Furthermore, there was no association between GSTP1 A/G gene polymorphism and the risk of lung cancer in Caucasians, and East-Asians. In conclusion, GSTP1 G allele is associated with the lung cancer susceptibility. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of lung cancer should be performed in the future.

Association of GSTP1 gene (I105V) polymorphism with acute leukaemia

Glutathione S-transferase P1 (GSTP1) enzyme plays a key role in biotransformation and bioactivation of certain environmental pollutants such as benzo[a]pyrene-7, 8-diol-9, 10-epoxide (BPDE) and other diol epoxides of polycyclic aromatic hydrocarbons (Hengstler et al. 1998) and catalyses detoxification of base propanols that arise from DNA oxidation thus offering cellular protection against oxidative stress. GSTP1 gene belongs to the pi class gene family, located on chromosome 11q13 (Autrup 2000). It comprises of seven exons (Morrow et al. 1989; Bora et al. 1997) and codes for cytosolic GST enzyme (Fryer et al. 1986). The first polymorphism identified is an A–G polymorphism at nucleotide 313 in exon 5 of GSTP1 gene which leads to an amino acid substitution of isoleucine (IE) by valine (val) at 105 amino acid position (Ile105Val). This substitution results in three GSTP1 genotypes: they are isoleucine/isoleucine (Ile/Ile) homozygous wildtype, isoleucine/valine (Ile/Val) heterozygote and valine/valine (Val/Val) homozygous variant.GSTP1 codon 105 polymorphism might play an important role in leukaemiogenesis, as it potentially alters protein function, diminishing its detoxification ability for certain mutagens and carcinogens, which could result in increased DNA damage and mutation, and a greater risk of developing cancer. Biochemical studies indicated that GSTP1 Val105 allele has a lower thermal stability than GSTP1 Ile105 allele (Zimniak et al. 1994; Johanson et al. 1998), and Val homozygotes had a lower conjugating activity than Ile homozygotes, with heterozygotes displaying intermediate activity (Watson et al. 1998). Individuals with at least one Val allele at codon 105 of GSTP1 enzyme might have an underlying predisposition to cancer when exposed to environmentally derived

Glutathione S-Transferase P1 (GSTP1) gene polymorphism increases age-related susceptibility to hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms in the world. Genetic polymorphism has been reported to be a factor increasing the risk of HCC. Phase II enzymes such as glutathione s-transferases (GSTP1, GSTA1) play important roles in protecting cells against damage induced by carcinogens. The aim of this study was to estimate the relationship of the GSTP1 and GSTA1 gene polymorphisms to HCC risk and clinico-pathological status.MethodsPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure GSTP1 (A→G) and GSTA1 (C→T) gene polymorphisms in 386 healthy controls and 177 patients with HCC.ResultsNeither gene polymorphism was associated with the clinico-pathological status of HCC and serum expression of liver-related clinico-pathological markers. No association between the GSTA1 gene polymorphism and HCC susceptibility was found. However, in the younger group, aged ≤ 57 years, individuals with AG or GG alleles of GSTP1 had a 2.18-fold (95%CI = 1.09-4.36; p = 0.02) and 5.64-fold (95%CI = 1.02-31.18; p = 0.04) risk, respectively, of developing HCC compared to individuals with AA alleles, after adjusting for other confounders.ConclusionAG and GG alleles of GSTP1 gene polymorphisms may be considered as factors increasing the susceptibility to and risk of HCC in Taiwanese aged ≤ 57 years.

GST (GSTM1, GSTT1, and GSTP1) polymorphisms in the genetic susceptibility of Turkish patients to cervical cancer

This work investigates the role of glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and glutathione S-transferase P1 (GSTP1) enzymes and polymorphisms, which are found in phase II detoxification reactions in the development of cervical cancer. This study was conducted with 46 patients diagnosed with cervical cancer and 52 people with no cancer history. Multiplex PCR methods were used to evaluate the GSTM1 and GSTT1 gene polymorphism. However, the GSTP1 (Ile105Val) gene polymorphism was studied using a PCR-RFLP method. The patient and control groups were compared using a chi-square test with p<0.05. In the patient group, statistical significance was determined for gravidity (p=0.03), parity (p=0.01), and the number of living children (p=0.01) compared to the control group. The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphisms was evaluated. We observed that GSTM1 and GSTT1 null genotype frequencies were 54.3% and 32.6% respectively, while GSTP1 (Ile/Val), (Ile/Ile), (Val/Val) genotype frequencies were 52%, 44%, and 4%, respectively, in the cervical cancer patients. No statistical variation was determined between the control and patient groups in terms of GSTM1, GSTT1, and GSTP1 polymorphisms (p>0.05). Our results demonstrate that GSTT1, GSTM1, and GSTP1 polymorphisms are not associated with cervical cancer in Turkish patients.

Glutathione S-transferase P1 gene polymorphism associated with gastric cancer among Caucasians

Studies investigating the association between glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarise the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 10 case-control studies, which included 1161 gastric cancer cases and 2847 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [AA odds ratio (OR) = 1.14, 95% confidence interval (CI) = 0.91, 1.44; AG (OR=0.82, 95% CI = 0.66, 1.03); GG (OR = 1.11, 95% CI = 0.55, 2.24)] between gastric cancer and non-cancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly higher frequency of AA (OR = 1.53, 95% CI = 1.14, 2.06) and lower frequency of AG (OR = 0.70, 95% CI = 0.55, 0.89) than non-cancer patients among Caucasians. When stratifying by the location and Lauren’s classification of gastric cancer, we observed no statistically significant differences in genotype distribution. This meta-analysis suggests that the GSTP1 codon 105 polymorphism may be associated with gastric cancer among Caucasians.

CYP1A2, CYP2D6, GSTM1, GSTP1, and GSTT1 gene polymorphisms in patients with bladder cancer in a Turkish population

Genetic differences in the metabolism of xenobiotics have recently been suggested as modifiers of individual susceptibility to bladder cancer (BC). The objective of this study was to investigate the relationship between bladder tumor and variants of cytochrome p450 1A2 (CYP1A2) 734 C --> A, cytochrome p450 2D6 (CYP2D6) 1934 G --> A, glutathione S-transferase M1, (GSTM1 null), glutathione S-transferase T1 (GSTT1 null), and glutathione S-transferase P1 (GSTP1) I105 V. We investigated the distribution of these polymorphisms in 135 BC patients and in 128 age and sex-matched cancer-free controls. The polymorphisms were analyzed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay and the multiplex PCR method. Genotype and allele frequencies and their associations with BC risk, demographic factors, smoking status, and tumor stage were investigated. The prevalence of GSTT1 null genotype in cases was 23%, compared with 7% in the control group (OR = 3.94, 95% CI = 1.70-9.38, P = 0.001). There was no association between the studied polymorphisms of CYP1A2, CYP2D6, GSTM1, and GSTP1 genes and BC. There was an association between smoking status and BC. These data seem to indicate that GSTT1 gene polymorphism may be associated with BC in the Turkish population studied. Further studies will be needed to clarify the role of such variation in determining susceptibility to BC.

Polymorphisms of Microsomal Epoxide Hydrolase and Glutathione S-transferase P1 in a Male Turkish Population

Polymorphic genes encoding drug-metabolizing enzymes may account for interindividual differences in certain types of diseases especially cancer. In this study, microsomal epoxide hydrolase (EPHX1) and glutathione S-transferase P1 (GSTP1) gene polymorphisms were determined among 133 healthy males of a Turkish population. Frequencies of EPHX1 and GSTP1 gene polymorphisms were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) method. The observed genotype frequencies of EPHX1 exon 3 were Tyr113Tyr:50.4%, Tyr113His: 42.1%, His113His: 7.5% and EPHX1 exon 4 were His139His: 69.2%, His139Arg: 28.6%, Arg133Arg: 2.2%. GSTP1 exon 5 genotype frequencies were Ile105Ile: 58.7%, Ile105Val: 35.3%, Val105Val: 6.0% and GSTP1 exon 6 genotype frequencies were Ala114Ala: 85.0%, Ala114Val: 14.3%, Val114Val: 0.7%. These results reveal that the frequencies of EPHX1 and GSTP1gene polymorphisms in a small sampling of males within a Turkish population are similar to European Caucasian populations.