Predictive Role of Glutathione-S-transferase Gene Polymorphisms in Risk and Prognosis of Hepatocellular Carcinoma

Aim: We conducted a prospective study in an Chinese population to detect associations of GSTM, GSTT andGSTP polymorphisms with hepatocellular carcinoma (HCC), and analyze roles in determining survival outcome.Methods: A prospective follow-up study was conducted with 476 HCC patients and 481 controls collected fromMay 2005 to May 2007. All patients were followed up until the end of Dec. 2011. GSTM1, GSTT1 and GSTP1genotyping were performed by PCR-CTPP methods. Results: Null GSTM1 carriers had a 1.64 fold risk of HCCcompared with non-null genotype, while GSTP1 Val/Val carriers had a 93% increased risk over the GSTP1IIe/IIe genotype. The median follow-up time for the 476 patients was 34.2 months (range: 1 to 78 months).Individuals with null GSTM1 genotype had better survival of HCC than non-null genotype carriers ( HR=0.71,95%CI=0.45-0.95). Similarly, GSTP1 Val/Val genotypes had significant better survival than the GSTP1 IIe/IIegenotype (HR=0.34, 95%CI=0.18-0.65). Individuals carrying null GSTM1 and GSTP1 Val/Val who receivedchemotherapy had lower risk of death from HCC than those without chemotherapy. Conclusion: This studyindicated carriage of null GSTM1 and GSTP1 Val/Val genotypes to have roles in susceptibility to and survivalfrom HCC.     

Predictive Role of GSTs on the Prognosis of Breast Cancer Patients with Neoadjuvant Chemotherapy

Objective: To evaluate the predictive value of GST gene polymorphisms with regard to prognosis of breastcancer patients receiving neoadjuvant chemotherapy. Methods: A total of 159 patients were included in our studybetween January 2005 and January 2007. All the patients were followed up until January 2012. Genotypingwas based upon the duplex polymerase-chain-reaction with the PCR-CTPP method. Results: Patients withnull GSTM1 and GSTP1 Val/Val genotypes had significantly had better response rates to chemotherapy whencompared with non-null GSTM1 and GSTP1 Ile/ Ile genotypes (OR=1.96 and OR=2.14, respectively). Patientswith the GSTM1 null genotype had a longer average survival time and significantly lower risk of death thandid those with non-null genotypes (HR=0.66). Similarly, those carrying the GSTP1 Val/Val genotype had 0.54-fold the risk of death of those with GSTP1 Ile/ Ile (HR=0.54). Conclusion: A significant association was foundbetween GSTM1 and GSTP1 gene polymorphisms and clinical outcomes in breast cancer cases.     

Prognostic Significance of GSTP1, XRCC1 and XRCC3 Polymorphisms in Non-small Cell Lung Cancer Patients

Aim: Individual differences in chemosensitivity and clinical outcome in non-small cell lung cancer (NSCLC)patients treatment with platinum-based chemotherapy may be due to genetic factors. Our study aimed toinvestigate the prognostic role of GSTP1, XRCC1 and XRCC3 in NSCLC patients treated with chemotherapy.Methods: A total of 460 cases were consecutively selected from The Affiliated Hospital of Nantong Universitybetween Jan. 2003 to Nov. 2006, and all were followed-up until Nov. 2011. Genotyping of GSTP1 Ile105Val, XRCC1Arg194Trp, XRCC1 Arg399Gln and XRCC3 Thr241Met was conducted by duplex polymerase-chain-reactionwith confronting-two-pair primer methods. Results: Patients with GSTP Val/Val exhibited a shorter survivaltime, and had a 1.89 fold greater risk of death than did those with the IIe/IIe genotype. For XRCC1 Arg194Trp,the variant genotype Trp/Trp was significantly associated with a decreased risk of death from NSCLC whencompared with the Arg/Arg. Individuals carrying XRCC1 399Gln/Gln genotype had a longer survival time,with a lowered risk of death from NSCLC. Conclusion: This study indicated that GSTP1 Ile105Val, XRCC1Arg194Trp and XRCC1Arg399Gln genes have a role in modifying the effect of platinum-based chemotherapyfor NSCLC patients in a Chinese population. Our findings provide information for therapeutic decisions forindividualized therapy in NSCLC cases.     

The association of glutathione S‐transferase polymorphisms in patients with osteosarcoma: evidence from a meta‐analysis

Osteosarcoma is a life‐threatening malignancy that often occurs in teenagers. Numerous studies have reported glutathione S‐transferase polymorphisms are associated with osteosarcoma, but the results are inconclusive, partially because the sample size in each of published studies is relatively small. Therefore, we performed a meta‐analysis of the published studies to estimate the association more accurately. To preciously examine the association between the glutathione S‐transferase polymorphisms and osteosarcoma, we undertook a meta‐analysis of six case–control studies. The association between the glutathione S‐transferase polymorphisms and osteosarcoma risk was assessed by odds ratios together with their 95% confidence intervals using a fixed‐effects model or random‐effects model. In addition, hazard ratio was used to measure the relationship between glutathione S‐transferase polymorphisms and prognosis in patients with osteosarcoma. We found that there was significant association between the polymorphisms in GSTT1 or GSTM3 (AA versus BB) and osteosarcoma risk. In addition, there is no evidence of association on GSTM1, GSTT1, GSTP1 (IIe/IIe versus IIe/Val) or GSTP1 (IIe/IIe versus Val/Val) polymorphisms with prognosis in osteosarcoma. In conclusion, the GSTT1 and GSTM3 polymorphisms might influence osteosarcoma risk.     

GSTP1遗传多态性对铂类化疗敏感性的影响

研究谷胱甘肽-S-转移酶P1（glutathione S-transferases P1,GSTP1）基因第105位点的遗传多态性与恶性肿瘤患者对铂类药物化疗敏感性的关系。方法:收集50例经病理确诊且CT扫描证实有可测量病灶并接受以顺铂为主的化疗的恶性肿瘤患者,于化疗前抽取外周静脉血,采用基因测序的方法对GSTP1基因第105位点的单核苷酸多态性（single nucleotide polymorphisms,SNPs）进行检测,观察这些患者经2～4个周期化疗后的疗效,分析各基因分型与铂类药物化疗敏感性的关系。结果:GSTP1基因第105位点基因型的分布与病种无关（P>0.05）。携带GSTP1基因第105位密码子的Ile/Ile、Ile/Val和Val/Val 3种基因型的患者对铂类药物化疗有效率分别为20.0%、36.4%和87.5%,携带纯合突变型Ⅴal/Ⅴal基因分型的患者的敏感性明显高于携带另外2种基因分型的患者（P<0.05）。结论:GSTP1基因单核苷酸多态性可能与铂类药物化疗敏感性相关。      

Glutathione S-transferase P1 and DNA Polymorphisms with the Response to Chemotherapy and the Prognosis of Bone Tumor

Osteosarcoma is the most common primary bone malignancy in children and adolescents, and its clinical outcome is poor. We evaluated the response of GSTP1, ERCC1 and ERCC2 to chemotherapy among osteosarcoma patients, and the role of these genes on the prognosis of osteosarcoma. 187 patients with osteosarcoma were administered with methotrexate, cisplatin/adriamycin, actinomycin D, cyclophosphamide, or vincristine treatment. GSTP1, ERCC1 and ERCC2 polymorphism was genotyped by PCR-RFLP assay. The results showed the average survival time of 187 patients were 38.4 months. 97 patients showed response to neoadjuvant chemotherapy. The GSTP1 Val and ERCC2 A/A genotypes had significantly higher rates of response to chemotherapy, with adjusted OR (95% CI) of 2.19 (1.15-6.21) and 2.88 (1.14-13.25). Individuals with ERCC2 A/A genotype were likely to have a lower risk of death from oseosarcoma, and the adjusted HR was 0.32 (0.13-0.95). Our study indicated test of GSTP1 and ERCC2 Lys751Gln polymorphisms might be a candidate pharmacogenomic factors to be explored in the future to identify the osteosarcoma patients who might benefit from chemotherapy.     

Association of GSTP1 and RRM1 Polymorphisms with the Response and Toxicity of Gemcitabine-cisplatin Combination Chemotherapy in Chinese Patients with Non-small Cell Lung Cancer

Background: Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1)were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) werecorrelated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivityand clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatinregimens. Materials and Methods: DNA sequencing was used to evaluate genetic polymorphisms of GSTP1Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinicalresponse was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessedby 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents). Results:There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequencydistribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive grouphad higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the jointdetection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A + higheffective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicityshowed no correlation with the genotypes between two groups (p>0.05). Conclusions: Compared with singledetection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may bemore helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy.Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict theresponse and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.     

Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer

BACKGROUND: Members of the glutathione S-transferase (GST) superfamily are important in cellular defense mechanisms. These enzymes attach reduced glutathione to electrophilic groups in a wide variety of toxic compounds, including chemotherapeutic agents. Certain polymorphisms in GSTs are associated with changes in enzyme activity, sensitivity to chemotherapy, and overall patient survival. In a retrospective study, we investigated associations between common polymorphisms in genes for several GST subclasses (GSTP1, GSTT1, GSTM1) and survival of patients with metastatic colorectal cancer receiving 5-fluorouracil (5-FU)/oxaliplatin chemotherapy. METHODS: During 1998-2000, 107 previously treated patients with advanced colorectal cancer received 5-FU/oxaliplatin combination chemotherapy. Associations between deletion polymorphisms in GSTM1 and GSTT1 genes and between a polymorphism in the GSTP1 gene that generates an Ile(105)Val in the GSTP1 protein and survival were evaluated using relative risks (RRs) of dying and the log-rank test. All statistical tests were two-sided. RESULTS: Patients heterozygous for the GSTP1 polymorphism had an RR = 0.47 (95% confidence interval [CI] = 0.27 to 0.81) compared with patients homozygous for the GSTP1 (105)Ile allele. Patients homozygous for the mutant polymorphism had an RR = 0.16 (95% CI = 0.04 to 0.63). After adjustment for performance status and tumor site, the stratified RRs were 0.28 (95% CI = 0.07 to 1.10) for patients with two (105)Val alleles and 0.64 (95% CI = 0.36 to 1.16) for those with one (105)Val allele (P =.042). Patients with the (105)Val/(105)Val genotype survived a median of 24.9 months, those with the (105)Ile/(105)Ile genotype a median of 7.9 months, and those with the (105)Ile/(105)Val genotype a median of 13.3 months (P<.001). The GSTM1 and GSTT1 genotypes were not associated with survival or clinical response. CONCLUSIONS: The GSTP1 Ile(105)Val polymorphism is associated in a dose-dependent fashion with increased survival of patients with advanced colorectal cancer receiving 5-FU/oxaliplatin chemotherapy.     

Association between glutathione S-transferase pi polymorphisms and survival in patients with advanced nonsmall cell lung carcinoma

BACKGROUND: Glutathione S-transferase (GST) pi (GSTP1) is a detoxification enzyme with substrate specificity for both exogenous carcinogens and chemotherapy agents. Genetic polymorphisms of GSTP1 exon 5 (Ile105Val) and exon 6 (Ala114Val) appear to reduce this enzyme's activity. Previously, the authors reported that the exon 6 variant was associated with an increased risk of lung carcinoma, particularly among men, younger patients, and ever smokers. In this study, the authors hypothesized that variant GSTP1 genotype would result in reduced inactivation of chemotherapy agents and improved survival in patients with advanced-stage nonsmall cell lung carcinoma (NSCLC), a population that is likely to receive platinum-based chemotherapy. METHODS: Patients with Stage III and IV NSCLC who were enrolled in a molecular epidemiology study were identified, and a polymerase chain reaction-restriction fragment length polymorphism assay was used to genotype GSTP1 exons 5 and 6 in 424 patients and 425 patients, respectively. RESULTS: Patients who had the exon 6 variant genotype (Ala/Val or Val/Val) had significantly better survival compared with patients who had the wild type genotype (Ala/Ala; P = 0.037), with median survival of 16.1 months and 11.4 months, respectively. Multivariate analysis revealed a reduced adjusted hazard ratio (HR) of death associated with the exon 6 variant genotype of 0.75 (95% confidence interval [95% CI], 0.54-1.05). This protective association was observed in younger patients (younger than age 62 yrs; HR, 0.59; 95% CI, 0.57-0.97) and in males (HR, 0.64; 95% CI, 0.41-0.99). GSTP1 exon 5 genotype was not associated with survival. CONCLUSIONS: GSTP1 exon 6 variant genotypes may be associated with improved survival among patients with Stage III and IV NSCLC.     

GSTP1 Ile105Val polymorphism correlates with progression-free survival in MCRC patients treated with or without irinotecan: a study of the Dutch Colorectal Cancer Group

A Valine residue at position 105 of the GSTP1 protein results in decreased enzyme activity. As nuclear GSTP1 activity decreases irinotecan cytotoxicity, Val-allele carriers may benefit more from irinotecan chemotherapy. Our aim was to investigate the association of GSTP1 genotype with treatment outcome of irinotecan. Progression-free survival (PFS) and toxicity were determined in 267 metastatic colorectal cancer (MCRC) patients who were treated with first-line capecitabine (CAP) plus irinotecan (CAPIRI), or CAP single agent in a prospective randomised phase III trial (CAIRO). GSTP1 genotype was determined by Pyrosequencing. Patients receiving CAP showed a PFS of 6.6 (Ile/Ile), 6.0 (Ile/Val) and 6.5 months (Val/Val); compared to 7.0 (Ile/Ile), 8.8 (Ile/Val) and 9.2 months (Val/Val) with CAPIRI. Median PFS was 2.7 months longer in Val-allele carriers treated with CAPIRI compared to CAP (P=0.005). Patients with the Ile/Ile genotype showed similar PFS with CAPIRI and CAP (7.0 compared to 6.6 months, P=0.972). Toxicity did not differ significantly among genotypes. GSTP1 codon 105 polymorphism may be predictive for the response to irinotecan-based chemotherapy in patients with MCRC, with the Val-allele being associated with a better outcome. Ile/Ile genotype patients do not appear to benefit from the addition of irinotecan to CAP.     

Glutathione S-transferase P1 genotype and prognosis in Hodgkin's lymphoma.

PURPOSE: Glutathione S-transferase P1 (GSTP1) is a member of the GST enzyme superfamily that is important for the detoxification of several cytotoxic drugs and their by-products. A single nucleotide polymorphism results in the substitution of isoleucine (Ile) to valine (Val) at codon 105, causing a metabolically less active variant of the enzyme. We assessed the impact of the GSTP1 codon 105 genotype on treatment outcome in patients with Hodgkin's lymphoma. EXPERIMENTAL DESIGN: The Ile(105)Val polymorphism in the GSTP1 gene was analyzed using a PCR-RFLP technique. Ninety-seven patients with Hodgkin's lymphoma were included and associations with patient characteristics and treatment outcome were analyzed. RESULTS: The GSTP1 Ile(105)Val polymorphism was associated in a dose-dependent fashion with an improved failure-free survival in patients with Hodgkin's lymphoma (P = 0.02). The probability of 5-year survival for patients homozygous for the (105)Val/(105)Val GSTP1 genotype was 100%, for heterozygous patients 74% (95% confidence interval, 56-85), and for patients homozygous for the (105)Ile/(105)Ile genotype 43% (95% confidence interval, 23-61). The Cox multivariate analysis showed that GSTP1 codon 105 genotype was an independent prognostic factor. CONCLUSIONS: The GSTP1 genotype predicts clinical outcome in patients with Hodgkin's lymphoma.     

The Relation between Polymorphisms in Exon 5 and Exon 6 of GSTP1 Gene and the Risk of Lung Cancer in Iranian People

Objective: The GSTP1 gene, which is located on chromosome 11q13, consists of 7 exons and 6 introns. Thereare two polymorphisms in GSTP1 that have been exposed to a transposition for codon 105 (Ile/Val) and 114 (Ala/Val)in exons 5 and 6, which have been studied previously in relation to lung cancer. Since the level of GSTP1 expressionin lung tissues and other human epithelial tissues is high, GSTP1Val-105 polymorphism is recognized as a sensitivefactor for tobacco-related cancers, especially lung cancer. Methods: One hundred and twenty tissue block samplesof patients with lung cancers and 120 peripheral blood samples of the control group were obtained from two referralcancer centers in Tehran, Iran, from 2011 to 2016. Genomic DNA was extracted from tissue blocks and buffy coat ofstudy cases to detect SNP of GSTP1 gene using Tetra-primer ARMS-PCR. Results: There was a notable correlationbetween the incidence of lung cancer and variant Val105 (P-value=0.001; OR=2/6; 95% CI=1.49-4.53) and Ile105(P-value=0.003; OR=0.41; 95% CI=0.23-0.73). The odds ratio for lung cancer in the homozygous Ile105/Ile105genotype was 3.56 times higher than that of individual with heterozygous Ile105/Val105 (P-value<0.001; OR=3/56;95% CI=1.826-6.934) genotype, that was statistically significant. Furthermore, the results showed that there was nosignificant correlation between Ala114/Val114 genotypes and lung cancer. The BC (P-value=0.007; OR=0.16; 95%CI=0.04-0.61) and AA (P=0.001) genotypes were statistically significant (P-value <0.05); and for those who had AAgenotype, the odds ratio was almost six times higher than those with BC genotype. Conclusions: The study of GSTP1polymorphisms indicated that unlike the polymorphism in exon 5, the GSTP1 exon 6 polymorphism correlated withthe lung cancer risk in the select group of Iranian people. Likewise, the potential use of this genetic polymorphism asa lung cancer predictor is confirmed.     

GSTP1, ERCC1 and ERCC2 Polymorphisms,Expression and Clinical Outcome of Oxaliplatin-based Adjuvant Chemotherapy in Colorectal Cancer in Chinese Population

Aim: Platinum agents have shown to be effective in the treatment of colorectal cancer. We assessed whethersingle nucleotide polymorphisms (SNPs) in GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln might predictthe overall survival in patients receiving oxaliplatin-based chemotherapy in a Chinese population. Methods:SNPs of GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln in 335 colorectal cancer patients were assessedusing TaqMan nuclease assays. Results: At the time of final analysis on Nov. 2011, the median follow-up periodwas 37.7 months (range from 1 to 60 months). A total of 229 patients died during follow-up. Our study showedGSTP1 Val/Val (HR=0.44, 95% CI=0.18-0.98), ERCC1 C/C (HR=0.20, 95% CI=0.10-0.79) and ERCC2 G/G(HR=0.48, 95% CI=0.19-0.97) to be significantly associated with better survival of colorectal cancer. GSTP1Val/Val, ERCC1 C/C and ERCC2 G/G were also related to longer survival among patients with colon cancer,with HRs (95% CIs) of 0.41 (0.16-0.91), 0.16 (0.09-0.74) and 0.34 (0.16-0.91), respectively. Conclusion: GSTP1,GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln genotyping might facilitate tailored oxaliplatin-basedchemotherapy for colorectal cancer patients.     

GSTM1、P1基因多态对接受铂类药物辅助化疗的胃癌患者预后的影响

 目的探讨GSTM1、GSTP1基因多态与胃癌对铂类药物辅助化疗预后的关系。方法确诊的胃癌患者84例,采用铂类药物为主的方案进行辅助化疗;采用聚合酶链反应-连接酶检测反应检测GSTM1和GSTP1 Ile105Val基因多态。结果84例胃癌患者中,43例(51.2%)携带GSTM1缺失基因型;GSTP1 Ile/Ile、Ile/Val和Val/Val分别占61.9%、28.6%和9.7%。携带GSTP1 Ile/Val和Val/Val基因型的胃癌患者无复发生存率和总生存率均显著高于携带Ile/Ile基因型患者(P<0.05)。多因素分析结果显示,GSTP1多态是影响患者复发的独立危险因素(P<0.05)。结论GSTP1 Ile105Val基因多态与接受铂类药物辅助化疗的胃癌患者的预后有关。     

GSTM1和CYP1A1基因多态性与宫颈癌发生及发展的相关性

目的:探讨谷胱苷肽硫转移酶M1（GSTM1）和CYP1A1 Exon7基因多态性与宫颈癌发生发展的关系。方法:选取2013年5月至2015年5月我院收治的宫颈癌患者184例为宫颈癌组,203例进行体检的健康人群为参照组。用限制性片段长度多态性-聚合酶链反应（RFLP-PCR）检测所有受试者GSTM1和CYP1A1 Exon7基因型;记录无进展生存期（PFS）,并随访观察生存和死亡情况。结果:GSTM1分为野生型（wt）和突变缺失型（null）,CYP1A1 Exon7野生型为Ⅱe/Ⅱe,突变型包括突变纯合型（Val/Val）、突变杂合型（Ⅱe/Val）。宫颈癌组携带GSTM1突变型基因型比例与参照组间比较,差异无统计学意义（P＞0.05）;宫颈癌组携带CYP1A1 Exon7突变型基因型比例显著高于参照组（P＜0.05）,且携带突变型基因型个体患宫颈癌的风险是携带野生型基因型个体的2.333倍。GSTM1、CYP1A1 Exon7基因型与宫颈癌患者年龄、病理分期、肿瘤分化程度、肿瘤直径及淋巴结转移均无关（P＞0.05）,与患者病理类型有关（P＜0.05）。GSTM1、CYP1A1 Exon7突变型宫颈癌患者PFS中位数与野生型患者比较,差异均无统计学意义（P＞0.05）。GSTM1、CYP1A1 Exon7突变型宫颈癌患者基因型与宫颈癌患者预后无关（P＞0.05）。结论:GSTM1及CYP1A1 Exon7基因多态性是宫颈癌发生发展的危险因素,尤其是CYP1A1 Exon7突变型,为预防宫颈癌提供依据。     

Role of GSTM1 (Present/Null) and GSTP1 (Ile105Val) Polymorphisms in Susceptibility to Acute Lymphoblastic Leukemia among the South Indian Population

Acute lymphoblastic leukaemia (ALL) is the most common pediatric malignancy worldwide. The origin ofthis disease may be explained by a combination of genetic and environmental factors. Glutathione-s-transferasesare a multi-gene family of enzymes involved in the detoxification of a wide variety of environmental carcinogens.A total of 92 immunophenotyped cases (below 25 years of age) and 150 cord blood controls were here analysedby PCR for GSTM1(Present/Null) and RQ-PCR allelic discrimination assay for GSTP1(Ile105Val). We found asignificant increased risk for ALL with the GSTM1 null genotype (OR: 1.96, 95%CI=1.08-3.57), but no significantrisk was found with the GSTP1 (Ile/Val) genotype (OR: 1.32, 95%CI = 0.74-2.37) and the GSTP1 Val/Val genotype(OR: 1.41, 95%CI=0.5-3.96) alone. Combined analysis of GSTM1 and GSTP1 showed significant higher riskassociated with the GSTM1 (null/null) and GSTP1 [(Ile/Val)/ (Val/Val)] genotype (OR=2.78: 95%CI=1.16-6.69).     

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

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

Predictive potential of ABCB1, ABCC3, and GSTP1 gene polymorphisms on osteosarcoma survival after chemotherapy

Genetic polymorphisms in drug metabolism and transport genes can influence the pharmacokinetics and pharmacodynamics of chemotherapy drugs. We investigated the role of genes involved in metabolic and transport pathways in response to chemotherapy and clinical outcome of osteosarcoma patients. The association between the eight polymorphisms with response to chemotherapy and clinical outcome of patients was carried out by unconditional logistic regression analysis and Cox proportional hazard models. Of 186 patients, 98 patients showed good response to chemotherapy, 64 died, and 97 showed progression at the end of the study. Patients carrying ABCB1 rs1128503 TT genotype and T allele were more likely to have a good response to chemotherapy. ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were associated with poor response to chemotherapy. In the Cox proportional hazards model, after adjusting for potential confounding factors, patients carrying ABCB1 rs1128503 TT genotype and T allele were associated with lower risk of progression-free survival (PFS) and overall survival (OS). ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were correlated with high risk of PFS and OS. The ABCB1 TT and GSTP1 GG genotypes were significantly associated with a shorter OS. In conclusion, variants of ABCB1 rs128503, ABCC3 rs4148416, and GSTP1 rs1695 are associated with response to chemotherapy and PFS and OS of osteosarcoma patients; these gene polymorphisms could help in the design of individualized therapy.     

Lung cancer susceptibility and polymorphisms of glutathione-S-transferase genes in Hong Kong

OBJECTIVE: To study the potential role of genetic polymorphisms of glutathione-S-transferases GSTM1, GSTT1 and GSTP1 in susceptibility to lung cancer in Hong Kong Chinese. METHODS: 229 consecutive incident patients with a histological diagnosis of lung cancer from a regional hospital and 197 healthy population-based controls were recruited for this study between July 1999 and June 2001. Genetic polymorphisms of GSTT1 and GSTM1 were determined using PCR-based technique. RESULTS: The frequencies of GSTT1 and GSTM1 null genotypes were 51.8 and 59.4% in healthy controls and 63 and 54.7%, respectively, in lung cancer patients. GSTP1 Val105/Val105 genotype was found in only 1% of healthy controls. The risk for lung cancer with GSTT1 null genotype was significantly higher, adjusted odds ratio (OR) 1.69, 95% confidence interval (CI) 1.12-2.56, compared with those with the GSTT1 genotype; the increase in risk was found only in non-smokers. GSTM1 null genotype, combined GSTT1 and GSTM1 null genotype and GSTP1 Val105/Val105 genotype did not confer any increase risk for lung cancer. CONCLUSION: GSTT1 null genotype is associated with an increased risk for lung cancer in non-smoking Chinese in Hong Kong.     

Investigating the Role of Glutathione S- Transferase Genes,Histopathological and Molecular Subtypes,Gene-Gene Interaction and Its Susceptibility to Breast Carcinoma in Ethnic North- Indian Population

Background: Breast Cancer (BC) is a genetically and clinically heterogeneous disease including complex interactions between gene-gene and gene-environment components. This study aimed, to explore whether the Glutathione S- transferase (GSTs) gene polymorphism has role in BC susceptibility. We further evaluated the frequency of four subtypes of BC based on molecular classification followed by microscopic histological analysis to study the grades of invasive ductal carcinoma (IDC). Materials and Method: Polymorphism in GST genes in North-Indian BC patients was assessed by multiplex-PCR and PCR-RFLP methods. 105 BC patients and 145 healthy controls were enrolled for this study. Data was analyzed by calculating the odds ratio (OR) and 95% CI from logistic regression analyses. Results: Our findings revealed that GSTM1 null genotype (OR = 2.231; 95% CI = 1.332–3.737; p-value= 0.002) is significantly associated to BC risk in ethnic North- Indian population. However, the risk for BC susceptibility in North–Indians does not appear to be associated with GSTT1 null genotype. The GSTP1 (Val/Val) genotype (OR=1.545; CI=0.663-3.605; p-value= 0.314) was also found to be susceptible for BC risk. Combination of three high risk GST genotypes association exhibiting gene-gene interaction further confirmed the increased risk to BC in this region. Conclusions: The results of present study indicated that polymorphism in GSTM1 and rs1695 of GSTP1 genes may influence BC development among North-Indian women. Thus, the screening of GSTM1 and GSTP1 gene should be recommended for the earlier investigation for BC as a precautionary measure.