Glutathione S-transferase P1 Gene Research Articles

The GSTP1 gene variant rs1695 is not associated with an increased risk of multiple sclerosis.

We analyzed the allelic and genotypic frequencies of the glutathione-S-transferase P1 (GSTP1) rs1695 single nucleotide polymorphism (SNP) in 290 patients with multiple sclerosis (MS) and in 310 healthy controls. We found no significant association between the rs1695 variant and MS. Among MS patients, there was no relationship between the rs1695 variant and either gender, clinical type of MS or the age of onset of MS. These results suggest that the GSTP1 rs1695 polymorphism is not a risk factor for MS.

Association of Glutathione S-Transferase Gene Methylation with Risk of Schizophrenia in an Iranian Population

Background/Aim: It has been believed that epigenetic changes play a critical role in schizophrenia through improper interaction between genome and environmental risk factors. The aim of this case-control study was to investigate the association of the promoter hypermethylation status of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase P1 (GSTP1) genes with the risk of schizophrenia. Materials and Methods: Methylation-specific PCR was used to estimate DNA methylation in the blood of 80 patients with schizophrenia and 71 healthy controls. Results: Promoter hypermethylation analysis of GSTT and GSTP indicated a significant difference between individuals with methylated and unmethylated status [odds ratio (OR) = 0.339, 95% confidence interval (95% CI) = 0.14-0.8, p = 0.012 and OR = 0.308, 95% CI = 0.135-0.7, p = 0.005, respectively]. Conclusion: The present study supports the hypothesis that impairment in the promoter region of GSTT and GSTP genes by hypermethylation may increase the risk of schizophrenia.

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.

Regulation of epigenetic traits of the glutathione S-transferase P1 gene: from detoxification toward cancer prevention and diagnosis.

Glutathione S-transferases (GSTs) are phase II drug detoxifying enzymes that play an essential role in the maintenance of cell integrity and protection against DNA damage by catalyzing the conjugation of glutathione to a wide variety of exo- and endogenous electrophilic substrates. Glutathione S-transferase P1 (GSTP1), the gene encoding the pi-class GST, is frequently inactivated by acquired somatic CpG island promoter hypermethylation in multiple cancer subtypes including prostate, breast, liver, and blood cancers. Epigenetically mediated GSTP1 silencing is associated with enhanced cancer susceptibility by decreasing its “caretaker” gene function, which tends to promote neoplastic transformation allowing cells to acquire additional alterations. Thus, this epigenetic alteration is now considered as a cancer biomarker but could as well play a driving role in multistep cancer development, especially well documented in prostate cancer development. The present review discusses applications of epigenetic alterations affecting GSTP1 in cancer medicine used alone or in combination with other biomarkers for cancer detection and diagnosis as well as for future targeted preventive and therapeutic interventions including by dietary agents.

Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

ObjectiveWe investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients.Patients and MethodsA hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR) with corresponding 95% confidence interval (95%CI) was calculated.ResultsThe glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1–4.2, p = 0.032). The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4–34.7, p = 0.001). The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1–19.7, p = 0.001). The risk of bladder cancer development was 5.3–fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9–15.1, p = 0.002). Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9–22.5, p = 0.067).ConclusionNull or low-activity genotypes of the glutathione S-transferase A1, T1, and P1 did not contribute independently towards the risk of bladder cancer in males. However, in association with occupational exposure, low activity glutathione S-transferase A1 and glutathione S-transferase M1-null as well as glutathione S-transferase T1-active genotypes increase individual susceptibility to bladder cancer.

Assessment of the prognostic value of methylation status and expression levels of FHIT, GSTP1 and p16 in non-small cell lung cancer in Egyptian patients.

Methylation of tumor suppressor genes has been investigated in all kinds of cancer. Tumor specific epigenetic alterations can be used as a molecular markers of malignancy, which can lead to better diagnosis, prognosis and therapy. Therefore, the aim of this study was to evaluate the association between gene hypermethylation and expression of fragile histidine triad (FHIT), glutathione S-transferase P1 (GSTP1) and p16 genes and various clinicopathologic characteristics in primary non-small cell lung carcinomas (NSCLC). The study included 28 primary non-small cell lung carcinomas, where an additional 28 tissue samples taken from apparently normal safety margin surrounding the tumors served as controls. Methylation-specific polymerase chain reaction (MSP) was performed to analyze the methylation status of FHIT, GSTP1 and p16 while their mRNA expression levels were measured using a real-time PCR assay with SYBR Green I. The methylation frequencies of the genes tested in NSCLC specimens were 53.6% for FHIT, 25% for GSTP1, and 0% for p16, and the risk of FHIT hypermethylation increased among patients with NSCLC by 2.88, while the risk of GSTP1 hypermethylation increased by 2.33. Hypermethylation of FHIT gene showed a highly significant correlation with pathologic stage (p<0.01) and a significant correlation with smoking habit and FHIT mRNA expression level (p<0.05). In contrast, no correlation was observed between the methylation of GSTP1 or p16 and smoking habit or any other parameter investigated (p>0.05). RESULTS of the present study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC. FHIT methylation may play a role in lung cancer later metastatic stages while GSTP1 methylation may rather play a role in the early pathogenesis.

Glutathione S-transferase M1, T1 and P1 gene polymorphisms and the risk of developing type 2 diabetes mellitus in Egyptian diabetic patients with and without diabetic vascular complications

Background and aim of workPersistent oxidative stress is one of several factors that participate in the pathogenesis of type 2 diabetes mellitus (T2DM). Glutathione S-transferases (GSTs) are a family of antioxidant enzymes that exert important antioxidant roles in the elimination of reactive oxygen species. We aimed to assess the association of genetic polymorphisms in the GST isoenzymes M1, T1 and P1 with the risk of developing T2DM and its vascular related complications in Egyptian diabetic patients. Subjects and methodsFifty-four T2DM patients of whom twenty-seven were suffering from vascular complications were compared to fifty-one healthy volunteers. Null genotypes in the GST M1 and T1 genes were screened using polymerase chain reaction (PCR). The A313G single nucleotide polymorphism in the GSTP1 gene was detected using PCR–restriction fragment length polymorphism. ResultsNo significant differences were noted between diabetic cases and control group regarding frequencies of null genotypes of GSTM1 and GSTT1 genes (χ2p=0.631 and χ2p=0.832, respectively). Furthermore, both null genotypes were not associated with the risk of developing T2DM or its related vascular complications whether alone or in combination. The frequency of the heterozygous mutation (AG) in the A313G GSTP1 polymorphism among diabetic cases with and diabetic cases without vascular complications was significantly higher compared to the control group (p=0.023). The risk of developing T2DM was significantly higher in cases presenting with combined heterozygous GSTP1 and null GSTM1 genotypes (Odds ratio=6.285, 95% confidence interval=1.184–33.347, p=0.021). ConclusionOur results could point out to potential roles of GSTP1 polymorphism alone or combined with GSTM1 gene polymorphism in the pathogenesis of T2DM related oxidative stress. Screening for other functional GST gene polymorphisms is important to understand the impact of interaction of multiple genetic factors in the pathogenesis of T2DM.

Long-term administration and efficacy of oxaliplatin with no neurotoxicity in a patient with rectal cancer: Association between neurotoxicity and the GSTP1 polymorphism.

Neurotoxicity is one of the most frequent side-effects of oxaliplatin. Oxaliplatin-induced cumulative and dose-limiting neurotoxicity either results in dose reduction or decreases the patients’ quality of life. However, the symptoms of neurotoxicity often vary among patients. The current study presents the case of a male with rectal cancer, who was administered a cumulative oxaliplatin dose of >5,000 mg/m2 without developing neurotoxicity or allergic reactions. Consequently, this patient continued therapy with modified 5-fluorouracil, leucovorin and oxaliplatin treatment for four years, with stabilization of the disease. This case indicates that if oxaliplatin-containing chemotherapy shows efficacy with no toxicity, the long-term administration of oxaliplatin would be effective and tolerable. Previously, the analysis of genomic polymorphisms in drug target genes has been important for explaining interindividual variations in the efficacy and toxicity of anti-cancer drugs. In the present patient, the glutathione S-transferase P1 (GSTP1) gene polymorphism, which is involved in the detoxification of platinum drugs, was analyzed. The genotype of the present case has been revealed as wild type (Ile/Ile) genotype. In addition, the associations between oxaliplatin-induced neurotoxicity and the GSTP1 polymorphism were also assessed. Certain studies have demonstrated that oxaliplatin-induced neurotoxicity occurs more frequently in patients with the Ile/Ile genotype, while others have demonstrated that those patients with the Val/Val or Ile/Val genotypes are more likely to develop neurotoxicity. Therefore, correlation between the GSTP1 polymorphism and oxaliplatin-induced neurotoxicity remains controversial. Overall, further development of individualized chemotherapy with an analysis of genomic polymorphisms in the drug target genes is required for the prophylaxis oxaliplatin-induced neurotoxicity.

Genetic polymorphism of glutathione S-transferase P1 (GSTP1) in Delhi population and comparison with other global populations

Glutathione S-transferases (GSTs) belong to a super family of phase II detoxification enzymes, which play an important role in protecting cells from damage caused by endogenous and exogenous compounds by conjugating reactive intermediates with glutathione to produce less reactive water-soluble compounds. In the present study, we determined the frequencies of two polymorphisms in exon 5 and exon 6 of GSTP1 gene in 500 normal individuals from Delhi. GSTP1 polymorphism was analysed by PCR-RFLP using amplification refractory mutation system (ARMS) assay. Two polymorphic sites in GSTP1 (Ile105→Val105; Ala114→Val114) have been analysed simultaneously, which results in four alleles: GSTP1*A (wild-type Ile105; Ala114), GSTP1*B (Val105; Ala114), GSTP1*C (Val105; Val114) and GSTP1*D (Ile105; Val114). The GSTP1 allele frequency in Delhi population was 0.663, 0.248, 0.069, and 0.020 for GSTP1*A, GSTP1*B, GSTP1*C, and GSTP1*D respectively. The frequency of Ile105 and Val105 allele was 0.683 and 0.317 respectively and it was calculated for the purpose of comparison with published data where all the four alleles were not analysed. GSTP1 alleles from Delhi population were compared with reported frequencies from all over India, and from other ethnic groups worldwide. This study would provide a basic database for future genetic studies.

Polymorphism of the glutathione S-transferase P1 gene (GST-pi) in breast carcinoma.

Breast carcinoma is the most common cancer and cause of death among females worldwide, including Jordan. The risk factors for breast carcinoma are linked to DNA mutation and failure of DNA repair or detoxification systems. Identification of susceptibility factors that predispose individuals to breast carcinoma if they are exposed to particular environmental agents might give further insight into the etiology of this malignancy. The glutathione S-transferase (GST) enzyme family detoxifies carcinogenic compounds. Several genes that code for these enzymes are polymorphic, with particular genotypes previously shown to confer an increased carcinoma risk. The present study investigates GST-pi polymorphism in 100-tissue samples previously diagnosed as breast carcinoma, and in 48 non-cancer age-matched breast tissues, using the restriction fragment length polymorphism (RFLP) method for the polymerase chain reaction (PCR) product. Among breast cancer cases, 58%, 40% and 2% were homozygous (Ile/Ile), heterozygous (Ile/Val) and homozygous (Val/Val) respectively. In the control group, 58%, 37.5% and 4.2% were homozygous (Ile/Ile), heterozygous (Ile/Val), and homozygous (Val/Val) respectively. Our results did not support the involvement of GST-pi gene polymorphism in susceptibility to breast carcinoma in the tested North Jordanian female population.

Prostate cancer molecular detection in plasma samples by glutathione S-transferase P1 (GSTP1) methylation analysis.

Prostate cancer (PCa) represents the most commonly diagnosed type of malignancy among men in Western European countries and the second cause of cancer-related deaths among men worldwide. Methylation of the CpG island has an important role in prostate carcinogenesis and progression. The purpose of the study was to analyse the diagnostic value of aberrant promoter hypermethylation of the gene for glutathione S-transferase P1 (GSTP1) in plasma DNA to discriminate between prostate cancer (PCa) and benign prostatic hyperplasia (BPH) patients by minimally invasive methods. Aberrant promoter hypermethylation was investigated in DNA isolated from plasma samples of 31 patients with diagnostic of PCa and 44 cancer-free males (control subjects). Extracted genomic DNA was bisulfite treated and analyzed using methylation-specific polymerase chain reaction (MS-PCR) technique. Hypermethylation of the GSTP1 gene was detected in plasma samples from 27 of 31 (92.86%) patients with PCa. Genomic DNA from plasma samples from the 44 controls without genitourinary cancer revealed promoter hypermethylation of GSTP1 gene in 3 (10.6%) of the 44 patients. Receiver operating curve (ROC) included clinico-pathological parameters such as: serum PSA levels, pathological stage, Gleason score, hypermethylation status of GSTP1 gene, and it gave a predictive accuracy of 93% with a sensitivity and specificity of 95% and 87%, respectively. In this study, we have evaluated the ability of GSTP1 gene to discriminate between PCa and BPH patients in genomic DNA from plasma samples by non-invasive methods.

ShRNA-mediated GSTP1 gene silencing enhances androgen-independent cell line DU145 chemosensitivity

Design short hairpin RNA (shRNA) interference sequence to silence glutathione S-transferase P1 (GSTP1) gene of androgen-independent prostate cancer cell line DU145, and then to explore its effect on sensitivity to chemotherapeutics. Target sequence was picked up to form the shRNA. DU145 cell was divided into five groups according to the shRNA added for transfection: shRNA255, shRNA554, shRNA593, negative-shRNA and blank group. Fluorescence microscope was used to pick up the shRNA with the highest transfection ratio. Western blotting and RT-PCR were taken to pick up the shRNA with the best gene silencing result. 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay and terminal de-oxynucleotidyl transferase-mediated dUTP nick end-labeling assay were used to detect survival ratio and apoptosis ratio of DU145 administered of fluorouracil (5-FU) or paclitaxel (PA) at different concentrations before and after shRNA transfection. Three different shRNA oligonucleotides (shRNA255; shRNA554; shRNA593) targeting the coding sequence of GSTP1 mRNA and one negative control shRNA were constructed. The transfection ratio of shRNA554 (76.2 ± 0.68 %) was higher than that of shRNA255 (63.3 ± 1.04 %) (P < 0.01) or shRNA593 (72.7 ± 0.33 %) (P < 0.01). After transfection of shRNA554, the mRNA and protein of level were the lowest, P < 0.01. The survival ratio of DU145 administered with 5-FU of different concentrations (30, 60, 120, 240 μg/ml) declined after transfection (P < 0.01). Besides, the apoptosis ratio increased after transfection (P < 0.01). Similarly the survival ratio of DU145 administered with PA of different concentrations (0.2, 2, 10, 20 μg/ml) declined (P < 0.01) and the apoptosis ratio increased (P < 0.01) after transfection. The gene GSTP1 silence via shRNA transfection to androgen-independent prostate cancer cell line DU145 enhances the sensitivity to chemotherapeutics.

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.

Association between GSTP1 Ile105Val polymorphism and glioma risk: A systematic review and meta-analysis

Glutathione S-transferase P1 (GSTP1) gene Ile105Val polymorphism has been suggested to be involved in the development of glioma. However, the results from the studies regarding the association between GSTP1 Ile105Val polymorphism and glioma risk have been inconsistent. Thus, we performed a meta-analysis to investigate this association. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated using random or fixed effects model. Nine studies with 2,078 cases and 3,970 controls were finally included into this meta-analysis. The results suggested there was no association between GSTP1 Ile105Val polymorphism and glioma risk under recessive model (OR = 1.138, 95%CI = 0.966-1.341, Pheterogeneity = 0.088, P = 0.123). Subgroup analyses by ethnicity showed there was also no association between GSTP1 Ile105Val polymorphism and glioma risk in mixed populations under recessive model (OR = 1.199, 95%CI = 0.928-1.549, Pheterogeneity = 0.060, P = 0.166) and Caucasian populations (OR = 1.097, 95%CI = 0.885-1.360, Pheterogeneity = 0.186, P = 0.398). In conclusion, the meta-analysis suggests that there is no association between GSTP1 Ile105Val polymorphism and glioma risk. However, more well-designed and larger studies are needed to further assess this association.

Quantitative assessment of the association between GSTP1 gene Ile105Val polymorphism and susceptibility to hepatocellular carcinoma

Glutathione S-transferase P1 (GSTP1) gene Ile105Val polymorphism has been suggested to be involved in the development of cancer. However, the results from the studies regarding the association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk have been inconsistent. Thus, we performed a meta-analysis to investigate the association. Published literature from PubMed, Chinese Biomedical Literature, and Wanfang databases was searched for eligible publications. Pooled odds ratios (ORs) with 95 % confidence intervals (95 %CIs) were calculated using random- or fixed-effects model. Six studies with a total of 1,843 participants were finally included into this meta-analysis. The results suggested there was no association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk under all genetic models (for ValVal vs. IleIle, OR = 0.79, 95 %CI 0.48-1.29, P = 0.341; for IleVal vs. IleIle, OR = 1.05, 95 %CI 0.84-1.30, P = 0.678; for the dominant model, OR = 0.91, 95 %CI 0.68-1.20, P = 0.498; and for the recessive model, OR = 0.76, 95 %CI 0.47-1.24, P = 0.269). Subgroup analyses by ethnicity showed there was also no association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk in Asians under all genetic models (All P values were more than 0.05), but GSTP1 Ile105Val polymorphism was associated with decreased risk of hepatocellular carcinoma in European under the recessive model (ValVal vs. IleVal/IleIle) (OR = 0.44, 95 %CI 0.20-0.98, P = 0.044). In conclusion, the meta-analysis suggests that there is little evidence for the association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk. However, more well-designed studies are needed to further assess this association.

Molecular Detection of Prostate Cancer by Methylation-Specific Polymerase Chain Reaction from Urine Specimens

Summary Background: Prostate cancer (PCa) represents the second most prevalent malignancy among males, which is characterized by a high mortality rate. The aim of our study was to evaluate the methylation status of glutathione S-transferase P1 (GSTP1) in urine specimens from males with PCa and benign prostatic hyperplasia (BPH) and its usefulness in distinguishing between males with PCa and BPH by noninvasive methods. Methods: Voided urine specimens were collected from 65 patients with PCa and 45 patients with BPH. Genomic DNA was isolated and subjected to bisulfite modification. Methylation status of the GSTP1 gene was determined by conventional methylation-specific polymerase chain reaction (MSP) analysis. Results: Promoter hypermethylation of the GSTP1 gene in voided urine samples was found in 63 of 65 (97%) males with PCa and in 5 of 45 (11%) males with BPH. The sensitivity and specificity of GSTP1 in discriminating between PCa and BPH males were 98% and 89%, respectively. Conclusions: Gene analysis of GSTP1 using conventional MSP in urine specimens can be used as a noninvasive biomarker to distinguish between men with malignant and benign prostatic diseases.

Association between GSTP1 Ile105Val polymorphism and oxaliplatin-induced neuropathy: a systematic review and meta-analysis

The association between glutathione-S-transferase P1 (GSTP1) Ile105Val polymorphism and oxaliplatin-induced neuropathy has been investigated in a number of published studies. However, most of these studies were based on small sample sizes and the results remained inconsistent. To assess the relationship between GSTP1 gene Ile105Val polymorphism and its susceptibility to oxaliplatin-induced neuropathy, a meta-analysis of previous studies was conducted. Two investigators independently searched studies published up to December 2012 from the databases of PubMed, EMBASE and The Cochrane Library. The pooled effect was calculated as odds ratio (OR) and corresponding 95% confidence intervals (CIs) using fixed-effect or random-effect model. Twelve prospective trials and two retrospective clinical trials involving 2,191 participants met the inclusion criteria. Combined analyses of these studies showed no significant associations between GSTP1 Ile105Val polymorphism and oxaliplatin-induced neuropathy, yielding OR of 1.08 (95%CI 0.67-1.74, P=0.754) in dominant model. Similar results were also obtained in recessive model (OR=1.67, 95%CI 0.56-4.93, P=0.357) and allelic analysis (OR=1.22, 95%CI 0.67-2.24, P=0.513). Since significant heterogeneity across studies, the pooled effects were calculated by random-effect model. No evidence of publication biases was identified in this meta-analysis. This meta-analysis did not support the hypothesis that GSTP1 Ile105Val polymorphism was related to the occurrence of neurotoxicity in oxaliplatin-treated patients. Given the limited number of studies and potential bias, large-scale and well-designed clinical trials should be needed to confirm these hypotheses.

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.

Abstract 1932: Association of genetic variants with prostate cancer risk.

Abstract Background: Genetic alterations can contribute to the malignant transformation and progression of prostate cancer. We have previously shown a strong association between specific leptin gene alleles, elevated serum leptin level, and body mass index in subjects with prostate and breast cancer. These studies showing association with leptin suggest a strong link with obesity as an increased risk factor. Studies have shown that adipose tissue TNFa and leptin, which are both overexpressed in obesity, induces the production of acute phase reactants through their autocrine or endocrine role. When GSTP1 is inactivated, prostate cells appear to become more vulnerable to somatic alterations upon chronic exposure to genome-damaging stresses such as oxidants and electrophiles that are contributed by environment and lifestyle. Studies also show that the methylation status of glutathione S-transferase p1 (GSTP1) could individually distinguish prostate cancer from benign prostatic hyperplasia. Based on prior studies, it is possible that multi gene analysis can provide better diagnostic or prognostic values for prostate cancer. Methods: In this study, we screened leptin gene markers, TNFa, GSTP1 and BCCIP(TOK-1A) in 126 prostate cancer and normal healthy age &amp; sex matched controls (Prostate cases: Age range 45-94, Mean age 73.3 Control males: Age range 65-98, Mean age 73.5). Polymerase chain reaction was used to amplify Leptin, TNF-308 and GSTP1 genes and the products are analyzed using 3130 Genetic analyzer and PCR-RFLP methods. Statistical analysis was performed using the SPSS/PC statistical program (version 10.0 for Windows; SPSS, Inc.,Chicago, IL). Relationships between two groups and genotype variables were assessed by Pearson's correlation coefficient. Conclusions: Prostate cancer is a complex, heterogeneous disease and there a variety of gene-based biomarkers that have been associated with prostate cancer. Our results show strong association of leptin (p&amp;lt;0.006), GSTP1 (p&amp;lt;0.023) with prostate cancer. Individually TNF and BCCIP showed a modest association but TNF/BCCIP gene interaction had a significant effect on prostate cancer risk and disease progression suggesting a multigene model for prostate cancer screening. Citation Format: Radhika G. Andavolu, Jean-Luc Cardenas, Ross Shore, Zach Rubin, James MacMurray, Krishna Kanth Chiravuri, Murthy VS Andavolu, Svetlana Rubakovic. Association of genetic variants with prostate cancer risk. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1932. doi:10.1158/1538-7445.AM2013-1932

Glutathione S-transferase P1 Ile105Val polymorphism contributes to increased risk of gastric cancer in East Asians

Glutathione S-transferase P1 (GSTP1) is an important enzyme playing critical roles in the phase II detoxification pathway. There were many studies investigating the association between GSTP1 gene Ile105Val polymorphism and gastric cancer risk, but studies from East Asians reported inconsistent findings. We performed a meta-analysis to investigate the association in East Asians. Published literature from PubMed and Chinese Biomedical Literature databases were searched for eligible publications. Pooled odds ratios (ORs) with 95 % confidence intervals (95 %CIs) were calculated using random or fixed-effect model according the between-study heterogeneity. A total of 12 studies with 2,552 cases and 5,474 controls were finally included into the meta-analysis. Meta-analysis of those 12 studies showed that there was an obvious association between GSTP1 Ile105Val polymorphism and gastric cancer risk in East Asians under three genetic models (for valine vs. isoleucine, OR=1.32, 95 %CI 1.05-1.66, P=0.015; for ValVal vs. IleIle, OR=2.00, 95 %CI 1.34-2.98, P=0.001; for the recessive model, OR=1.96, 95 %CI 1.35-2.83, P<0.001). Sensitivity analysis by removing one study at a time suggested the pooled results were stable under the three genetic models above. There was no risk of publication bias. In conclusion, the meta-analysis suggests that there is a strong evidence for the association between GSTP1 Ile105Val polymorphism and increased risk of gastric cancer in East Asians and contributes to increased risk of gastric cancer in East Asians.