Background: Some studies have investigated the association of GSTM1, GSTT1, GSTM3, and GSTP1 polymorphisms with susceptibility to osteosarcoma; however, these studies results are inconsistent and inconclusive. In order to drive a more precise estimation, the present case-control study and meta-analysis was performed to investigate association of GSTM1, GSTT1, GSTM3, and GSTP1 polymorphisms with osteosarcoma. Methods: Eligible articles were identified by a search of several electronic databases for the period up to May 5, 2018. Odds ratios were pooled using either fixed-effects or random effects models. Results: Finally, a total of 24 case-control studies with 2,405 osteosarcoma cases and 3,293 controls were included in the present meta-analysis. Overall, significantly increased osteosarcoma risk was found when all studies were pooled into the meta-analysis of GSTT1 (Null vs. Present: OR= 1.247 95% CI 1.020-1.524, P= 0.031) and GSTP1 polymorphism (B vs. A: OR= 8.899 95% CI 2.722-29.094, P≤0.001). In the stratified, significantly increased osteosarcoma risk was observed for GSTT1 polymorphism among Asians (Null vs. Present: OR= 1.300 95% CI 1.034-1.635, P= 0.025), but not among Caucasians. Conclusions: This meta-analysis demonstrated that GSTP1 and GSTT1 null genotype are associated with the risk of osteosarcoma. Future large welldesigned epidemiological studies are warranted to validate our results.

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

OBJECTIVE: to compare the polymorphism of the Glutathione S-transferase theta 1 (GSTT1) and Glutathione S-transferase mu 1 (GSTM1) genes from the tumor area with the proximal and distal margins of stomach specimens resected from patients with gastric cancer, and to investigate the presence of Epstein-Barr virus (EBV) DNA and Helicobacter pylori.
METHODS: we prospectively collected tissue specimens from the tumor area and from the proximal and distal resection margins of the stomachs of ten patients with gastric adenocarcinoma who underwent gastrectomy with D2 lymphadenectomy, and submitted these specimens to DNA extraction. We compared the tumor area with the proximal and distal margins of the resected stomachs for polymorphism of GSTT1 and GSTM1 genes and investigated the presence of EBV-DNA and H. pylori. We used the p53 exon 5 gene as an internal control of the multiplex PCR reaction.
RESULTS: in one patient, we detected null GSTT1 and GSTM1 genotypes in the tumor area, in contrast to the presence of both genes in the proximal and distal margins. We found EBV-DNA and H. pylori in the tumor area and also in the proximal and distal margins. In another patient, the proximal margin was negative for GSTT1, and EBV-DNA was negative in the distal margin. In three patients, EBV-DNA was negative only in the distal margin.
CONCLUSION: this is the first report where different genotypes, EBV-DNA and H. pylori infection were observed in the same patient, indicating a probable deletion of these genes in response to tumor progression and intratumoral heterogeneity.

Several studies linked between pesticides exposure and development of liver cancer, through several mechanisms inform of genotoxicity, cytotoxicity, tumor promotion, immunotoxicity and hormonal actions. This study aimed to estimate novel biomarkers for early prediction of liver malignancy due to occupational exposure to pesticides in two groups of workers with different socioeconomic standard (highly educated urban researchers and low educated rural pesticides sprayers). This study included 50 urban researchers and 50 rural pesticides sprayers occupationally exposed to pesticides. They were compared with 50 non-exposed urban researchers and 50 non-exposed rural subjects. Several tumor biomarkers were estimated; P53 protein, Alfa fetoprotein (AFP), and Alpha-L-fucosidase (AFU). Additionally, telomerase enzyme activity, Relative telomere length (RTL), and DNA damage using comet assay were measured. Furthermore, the glutathione-S-Transferase (GST) gene polymorphisms were identified for both exposed groups. Statistical analysis revealed elevated level of tumor biomarkers among exposed subjects relative to control groups in spite of being within the normal range. Increase in the DNA damage was detected, with shortening of telomere length and decrease in telomerase enzyme activity in pesticides-exposed subjects compared to their controls. Most of these changes were related to the levels of butyrylcholinesterase. Subjects with GSTT1 genotype were suggested to be more susceptible to hepatic carcinogenicity. Telomere relative length and comets assay together with GST genes polymorphisms could be used as early predictors for liver cancer susceptibility among pesticides exposed workers.

Microsomal epoxide hyrolase 1 (EPHX1) is a critical biotransformation enzyme and participants in both the detoxification and activation of potentially genotoxic epoxides. In this study, we firstly aimed to investigate the role of EPHX1 in the chemoresistance of acute myeloid leukemic cells to aclarubicin (ACM) and mitoxantrone (MIT). EPHX1 mRNA expression and prognosis were measured in acute myeloid leukemia (AML) patients, and the function of EPHX1 in leukemic cell viability and apoptosis induced by ACM and MIT was also measured. Our results found that EPHX1 expression is obviously associated with recurrence rate, overall survival and time of obtaining first complete remission in AML patients. EPHX1 silencing promoted ACM and MIT induced decrease in cell viability and cell apoptosis of HL-60, K562, and THP-1 that was inhibited by EPHX1 overexpression. EPHX1 reduced the susceptibility of leukemic cells to ACM and MIT by regulating drug-metabolizing enzymes (CYP1A1, GSTM1, and GSTT1) and apoptotic signaling (Bax, Bcl-2, Caspase-3, Caspase-9, and PARP1). Moreover, Nrf2 overexpression significantly increased EPHX1 expression and leukemic cell viability and decreased leukemic cell apoptosis. Taken together, we summarized the recent findings about the chemoresistance-promoting role of EPHX1, and the potential of targeting EPHX1 was proposed to counteract drug resistance in leukemia treatment.

We observed inconsistent conclusions regarding the genetic role of glutathione S-transferase gene polymorphisms, including glutathione S-transferase M1 (

BACKGROUND: We conducted a meta-analysis to evaluate the relationship between the glutathione S-transferase μ1 (GSTM1)- and glutathione S-transferase θ1 (GSTT1)- null genotypes and susceptibility to bladder cancer.
METHODS: We identified association reports from the databases of PubMed, Embase, the Cochrane Library and the China Biological Medicine Database (CBM disc) on July 1, 2017 and synthesized eligible investigations. Results were expressed using odds ratios (ORs) for dichotomous data, and we also calculated 95% confidence intervals (CIs).
RESULTS: In this meta-analysis, we found that the GSTM1-null genotype was associated with bladder cancer risk in the overall population, and individually in whites, Africans and Asians (overall population: OR = 1.40, 95% CI: 1.31-1.48, P<0.00001; whites: OR = 1.39, 95% CI: 1.26-1.54, P<0.00001; Africans: OR = 1.54, 95% CI: 1.16-2.05, P = 0.003; Asians: OR = 1.45, 95% CI: 1.33-1.59, P<0.00001). The GSTT1-null genotype was associated with bladder cancer risk in the overall population, but not in whites, in Africans or Asians (overall population: OR = 1.11, 95% CI: 1.01-1.22, P = 0.03; whites: OR = 1.16, 95% CI: 0.99-1.36, P = 0.07; Africans: OR = 1.07, 95% CI: 0.65-1.76, P = 0.79; Asians: OR = 1.05, 95% CI: 0.91-1.22, P = 0.51). Interestingly, a dual-null GSTM1-GSTT1 genotype was associated with bladder cancer risk in the overall population and in Asians (overall population: OR = 1.48, 95% CI: 1.15-1.92, P = 0.002; Asians: OR = 1.62, 95% CI: 1.15-2.28, P = 0.006). In conclusion, the GSTM1-null, GSTT1-null and dual-null GSTM1-GSTT1 genotypes might be associated with the onset of bladder cancer, but additional genetic-epidemiological studies should be conducted to explore this association further.

Objective(s): Lung cancer, caused primarily by smoking, is one of the leading determinants of mortality throughout the world. Here we investigated the effects of polymorphisms in two enzymes, i.e., GSTT1 and GSTM1, related to the antioxidant defense line against carcinogens associated with lung cancer among a select group of Iranian people. Materials and Methods: One hundred and twenty lung cancer patients from two referral centers in Tehran, Iran, were recruited for comparison with 120 healthy controls. Genomic DNA was extracted from the FFPE tumor tissues of the select cases and peripheral blood buffy coats of healthy controls. The polymorphisms of GSTT1 and GSTM1 were investigated by multiplex polymerase chain reaction. Results: With the 240 samples studied, no specific relationship with lung cancer was discerned for the GSTM1 (P=0.35; OR=1/33; 95% CI=0.79-2.25) polymorphism, but the GSTT1 (P=0.005; OR=2.4; CI=1.32-4.35) gene polymorphism revealed a notable association on logistic regression, taking into account age and sex factors. Furthermore, the GSTT1 genotype distribution in patients with LSCC was different from that of healthy cases (P=0.006; OR=3.11; CI=1.38-7.04). The risk of developing lung cancer with the T0M1 genotype was 3.46 times higher than with T1M1 genotype (P=0.002; OR=3.46; CI=1.61-7.46). Moreover, the risk of developing LSCC cancer in people with T0M1 genotypes was significantly elevated (P=0.004; OR=4.5; CI=1.62-12.52). Conclusion: Unlike GSTM1, the GSTT1 genotype distribution is associated with the incidence of lung cancer in Iranian people. Different types of lung cancer appear to show various correlations with GST polymorphisms in this regard.

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

AIM: To evaluate the association between polymorphisms in glutathione S transferases (GSTs) and the risk of sporadic colorectal cancer (SCRC), tumor progression and the survival of patients.
METHODS: A case-control study of 970 individuals from the Brazilian population was conducted (232 individuals from the case group with colorectal cancer and 738 individuals from the control group without a history of cancer). PCR multiplex and PCR-RFLP techniques were used to genotype the GST polymorphisms. The tumors were categorized according to the TNM classification: tumor extension (T), affected lymph nodes (N), and presence of metastasis (M). Logistic regression, multiple logistic regression and survival analysis were used to analyze the data. The results are presented in terms of odds ratio (OR) and 95% confidence interval (CI). The level of significance was set at 5% (
RESULTS: Age equal to or over 62 years (OR = 8.79; 95%CI: 5.90-13.09,
CONCLUSION: Females aged 62 years or older are more susceptible to SCRC. Polymorphisms of

BACKGROUND Previous studies have shown an association with glutathione S-transferase (GST) gene polymorphisms in patients with non-small cell lung cancer (NSCLC) and treatment response. This study aimed to undertake a literature review and meta-analysis of GST gene polymorphisms, including GSTT1, GSTM1, and GSTP1 IIe105Val, and the treatment response to cisplatin-based chemotherapy in patients with NSCLC. MATERIAL AND METHODS A literature search was undertaken of the main medical publication databases for publications, up to March 2017, on the association between GSTT1, GSTM1, and GSTP1 IIe105Val polymorphisms and the clinical outcome in patients with NSCLC treated with cisplatin-based chemotherapy. A random fixed-effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate the associations, considering multiple genetic models. A subgroup analysis according to ethnicity was performed. RESULTS Twenty-three published studies were identified that showed that both the null GSTM1 and the GG genotype of GSTP1 IIe105Val were associated with improved treatment response to cisplatin-based chemotherapy (GSTT1 present/null: OR=1.328; 95% CI, 1.074-1.643) (GSTP1 GG + AG vs. AA: OR=0.596; 95% CI, 0.468-0.759). In subgroup analysis, the GSTP1 polymorphism was significantly associated with treatment response in East-Asian patients, but not in Caucasian patients. CONCLUSIONS Meta-analysis showed that the GG genotype of GSTP1 IIe105Val and the null GSTM1 genotype were associated with an improved treatment response to cisplatin-based chemotherapy in patients with NSCLC, especially in East-Asian patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the world. Despite improvements in screening for early diagnosis, CRC is one of the leading causes of cancer deaths.
OBJECTIVES: The aim of the study was to determine a potential association between the frequency of GSTM1 and GSTT1 null genotypes and the risk of CRC in the Polish population. Moreover, we analyzed the clinical parameters with the glutathione S-transferase (GST) gene polymorphisms in patients with CRC.
MATERIAL AND METHODS: The study was conducted on 512 Caucasians, including 279 patients (105 women and 174 men) with CRC. DNA from peripheral blood was extracted and the multiplex polymerase chain reaction (PCR) technique was used for glutathione S-transferase theta (GSTT1) and mu (GSTM1) gene deletion genotyping.
RESULTS: We found no statistically significant differences in the frequency of the GST gene polymorphisms in patients with CRC and controls. The prevalence of the GSTM1*0 variant in the test subjects was higher than in controls (45.9% vs 42.9%; p > 0.05). The frequency of the GSTT1*0 variant was also higher in patients with CRC compared to the control population (21.1% vs 18.9%; p > 0.05). In addition, the effect of the GSTM1 and GSTT1 polymorphisms on the incidence of CRC was also analyzed. There was a slight, but not statistically significant, increase of the risk of colon cancer for the GSTM1*0 and GSTT1*0 variants. Moreover, we examined the GST genotype due to the cancer TNM classification and the location of the primary tumor. Statistically significant differences in the distribution of the GSTT1*0 and GSTT1*1 genotypes in both the stage and the location of the primary tumor were observed.
CONCLUSIONS: It is suggested that the GSTT1 polymorphism may have an impact on the severity of the tumor and its location.

We investigated the immunohistochemical staining characteristics of cytochrome P450 1A1 (CYP1A1), CYPB1, CYP2E1, and glutathione S-transferase P1 (GSTP1), GSTT1, GSTO1, GSTK1 in colon tumor and surrounding normal colon tissues. Tissues were obtained from 47 patients with colon adenocarcinoma and the staining intensity of tumor and control tissues was compared. CYP1A1, CYP1B1, CYP2E1, GSTP1, GSTT1, GSTO1 and GSTK1 expressions in colon cancer cells were significantly greater than those in normal colon epithelial cells. No significant relation was found between the isoenzyme expressions and age, gender, smoking status, tumor grade and tumor stage. The higher expressions of CYP1A1, CYP1B1, CYP2E1, GSTP1, GSTO1, GSTT1 and GSTK1 in tumor than in normal colon tissues may be important for colon cancer progression and development.

BACKGROUND: Certain forms of chemoradiotherapy generate toxic reactive oxygen species, which may be ameliorated by antioxidant enzymes such as glutathione S-transferase (GST). Genetic polymorphisms of GST may predict treatment outcomes and can be used as genetic marker to screen patients before treatment. We hypothesised an effect of GST polymorphisms on the response and toxicities produced by chemoradiation therapy.
MATERIALS AND METHODS: GST polymorphisms were determined by multiplex polymerase chain reaction and PCR-restriction fragment length polymorphism (PCR-RFLP) in 227 women with cervical cancer receiving cisplatin based chemoradiotherapy. Treatment response and toxicities were evaluated by standard internationally recognised criteria (RECIST and RTOG).
RESULTS: Severe (grade 3-4) gastrointestinal and haematological toxicities were present in 22 (9.4%) and 16 (7.0%) patients, respectively. GSTM1 null, GSTT1 null and GSTP1 AG genotypes brought marginally better non-significant associations. In single locus analysis GSTP1 AG and GG was linked to greatest risk of severe (grade 3-4) gastrointestinal toxicity (OR = 3.12, P = 0.035 and OR = 6.99, P = 0.01, respectively). In gene-gene interaction analysis, GSTM1 null-GSTP1 GG showed 4.2-fold higher risk of severe gastrointestinal toxicity (P = 0.014). GSTT1 null-GSTP1 AG reached statistical significance with a 3.9-fold higher risk of high grade gastrointestinal toxicity (P = 0.038).
CONCLUSIONS: Although no significant links were found between GST polymorphism and treatment response, null genotypes of GSTM1, GSTT1 and 'G' allele of GSTP1 bring a higher risk of severe gastrointestinal toxicity due to chemoradiation therapy in cervical cancer.

BACKGROUND: Association of GSTM1- and GSTT1-null genotypes, GSTP1 A/G gene polymorphism with renal cell carcinoma (RCC) susceptibility was detected, and the relationship between the GSTM1/GSTT1-null genotype and clinical TNM stages of RCC was assessed, using meta-analysis method.
METHODS: Association investigations according to eligibility criteria were searched and identified from the databases of Cochrane Library, PubMed, and Embase from establishment time of databases to July 1, 2017, and eligible reports were analyzed by meta-analysis. 95% confidence intervals (CI) were also detected, and odds ratios (OR) was used to express the results for dichotomous data.
RESULTS: This meta-analysis indicated that there was no an association between GSTM1-null genotype, GSTT1-null genotype, GSTP1 A/G gene polymorphism and RCC risk in the overall population of Caucasians or Asians. The dual GSTM1-GSTT1-null genotype was also not associated with RCC in the overall population of Caucasians. Interestingly, there was an association between the dual GSTM1-GSTT1-null genotype and the susceptibility of RCC in Asians. Relationship of the GSTM1-null genotype with clinical TNM stage of RCC was not observed in the overall population of Asians or Caucasians. In this meta-analysis, no association between the GSTT1-null genotype and clinical TNM stage of RCC was observed in Caucasians or Asians. Interestingly, GSTT1-null genotype was detected to be associated with the clinical TNM stages in patients with RCC in the overall population.
CONCLUSION: The dual GSTM1-GSTT1-null genotype is detected to be associated with the onset of RCC in Asians, and there is an association between the GSTT1-null genotype and the clinical TNM stages in patients with RCC in the overall population.

Epidemiological studies undertaken over the past decades reveal a gradual but progressive increase in the incidence and mortality attributable to lung cancer in the Islamic Republic of Iran, a sovereign state geographically situated at the crossroads of Central Eurasia and Western Asia. We identified references published in English and Persian through searches of PubMed, EMBASE, Web of Science, Scopus, and the Scientific Information Database (SID)-a specialized Iranian database, which indexes Iranian scientific journals-between inception and 15 September 2017. Of 1475 references identified through electronic searches, we reviewed the full text of 88 studies, and included 38 studies in the review. Potentially druggable NSCLC targets, which have been studied in Iran include EGFR, ALK, ERBB2, and KIT; but no studies were found, which examined the impact of MET, ROS1, BRAF, PIK3CA, and FGFR1 aberrations. We were able to identify some literature on DNA repair genes and xenobiotic metabolism, including TP53, TP63, ERCC2, XRCC2, SIRT1, PTEN, CYP1A1, CYP1B1, GSTT1, and GSTM1. We also found an increasing amount of research performed in relation to the tumor microenvironment and immune contexture, including CTLA4, MAGE, FOXP3, IFN-γ, and various interleukins, chemokines, and transcription factors; but did not identify any publication concerning the expression of PD-1/PD-L1 in lung cancer. Our survey of research performed in Iran has revealed a dearth of studies in topics, which are otherwise highly pursued in developed countries, but nevertheless, has begun to hint at a distinct biology of lung cancer in this part of the world.

Background: Epidemiological research has highlighted the global burden of primary liver cancer cases due to alcohol consumption, even in a low consumption country like India. Alcohol detoxification is governed by ADH1B, ALDH2, GSTM1 and GSTT1 genes that encode functional enzymes which are coordinated with each other to remove highly toxic metabolites i.e. acetaldehyde as well as reactive oxygen species generated through detoxification processes. Some communities in the population appears to be at greater risk for development of the liver cancer due to genetic predispositions. Methods: The aim of this study was to screen the arcadian population of central India in order to investigate and compare the genotype distribution and allele frequencies of alcohol metabolizing genes (ADH1B, ALDH2, GSTM1 and GSTT1) in both alcoholic (N=121) and control (N=145) healthy subjects. The gene polymorphism analysis was conducted using PCR and RFLP methods. Results: The allele frequency of ALDH2 *1 was 0.79 and of ALDH2*2 was 0.21 (OR:1.12; CI (95%): 0.74-1.71). The null allele frequency for GSTM1 was 0.28 (OR:0.85; CI (95%): 0.50-1.46) and for GSTT1 was 0.20 (OR:1.93; CI (95%): 1.05-3.55). No gene polymorphism for ADH1B was not observed. The total prevalence of polymorphisms was 3.38% for ALDH2, GSTM1 and GSTT1. Conclusion: The results of this study suggested that individuals of the Central India population under study are at risk for liver disorders due to ALDH2, GSTM1 and GSTT1 gene polymorphisms. This results may have significance for prevention of alcohol dependence, alcoholic liver disorders and the likelihood of liver cancer.

Determinants of interindividual variability in erlotinib pharmacokinetics (PK) and adverse events remain to be elucidated. This study with 50 Japanese non-small-cell lung cancer patients treated with oral erlotinib at a standard dose of 150 mg aimed to investigate whether genetic polymorphisms affect erlotinib PK and adverse events. Single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP1A1, CYP1A2, CYP2D6, CYP3A4, CYP3A5, UGT1A1, UGT2B7, GSTM1, and GSTT1) or efflux transporters (ABCB1, and ABCG2) were analyzed as covariates in a population PK model. The ABCB1 1236C>T (rs1128503) polymorphism, not ABCB1*2 haplotype (1236TT-2677TT-3455TT, rs1128503 TT-rs2032582 TT-rs1045642 TT), was a significant covariate for the apparent clearance (CL/F), with the TT genotype showing a 29.4% decrease in CL/F as compared with the CC and the CT genotypes. A marginally higher incidence of adverse events (mainly skin rash) was observed in the TT genotype group; however, patients with high plasma erlotinib exposure did not always experience skin rash. None of the other SNPs affected PK or adverse events. The ABCB1 genotype is a potential predictor for erlotinib adverse events. Erlotinib might be used with careful monitoring of adverse events in patients with ABCB1 polymorphic variants.

OBJECTIVE: To evaluate if variants in the genes CYP1A1 (T3801C and A4889G), CYP1B1 (G119T), GSTM1 (indel) and GSTT1 (indel) are associated with breast cancer (BC) among Mexican women.
MATERIALS AND METHODS: 952 incident cases with histologically confirmed BC were matched by age (± 5 years) and zone of residence with 998 healthy population controls. Genetic variants in genes CYP1A1, CYP1B1, GSTM1 and GSTT1were genotyped by allelic discrimination and multiplex PCR. In a subsample of women, 105 markers for ancestry were determined.
RESULTS: An increased BC risk, independent of other BC risk factors, was observed among carriers of CYP1B1 G119T genotype (T/T vs. G/G: OR=1.9; 95%CI 1.4-2.5).
CONCLUSION: Our results support the existence of genetic susceptibility for BC conferred by CYP1B1 G119T variant among Mexican women.

BACKGROUND: Published data regarding the association between GSTM1 and/or GSTT1 gene polymorphisms and esophageal cancer (EC) susceptibility remain inconclusive. To clarify these associations, a meta-analysis was conducted.
METHODS: We conducted a comprehensive search in PubMed, Embase, and the China National Knowledge Infrastructure (CNKI) for all such manuscripts published as of May 1, 2017. The pooled odds ratio (ORs) with confidence intervals (95% CI) were estimated for each study to assess the strength of the association. A subgroup analysis, a sensitivity analysis, and a publication bias analysis were also performed.
RESULTS: Data from 41 studies comprising 5291 EC cases and 8191 controls were available for analysis of the GSTM1 polymorphism, and data from 31 studies comprising 4330 EC cases and 6558 controls were available for analysis of the GSTT1 polymorphism. Analyses of the GSTM1 polymorphisms demonstrated that there was a significantly increased EC risk in GSTM1 null genotype carriers (OR = 1.319, 95% CI = 1.125-1.546, p for heterogeneity <0.001). In subgroup analyses by ethnicity, and categories of EC, a significantly increased EC risk was found in Asians (OR = 1.457, 95% CI = 1.212-1.751, p for heterogeneity <0.001) and patients whose histological type was unknown. Analyses of the GSTT1 polymorphisms indicated a positive correlation between the GSTT1 null genotype and the EC risk (OR = 1.233, 95% CI = 1.044-1.455, p for heterogeneity <0.001). In subgroup analyses stratified by ethnicity and categories of EC, similar statistical associations were observed in Asians, esophageal squamous cell carcinoma (ESCC) patients, and ESCC on Asian population. In the GSTM1-GSTT1 interaction analysis, we discovered remarkably enhanced EC risk for patients with the GSTM1 and GSTT1 dual null genotypes (OR = 1.962, 95% CI = 1.178-3.268, p for heterogeneity <0.001) compared with the reference GSTM1 and GSTT1 dual positive genotype.
CONCLUSIONS: We conclude that the GSTM1 and GSTT1 null genotypes are associated with increased genetic susceptibility to EC in the overall human population, particularly among Asians. In addition, our findings suggest that persons with a null genotype for both the GSTM1 and GSTT1 genes are at higher risk of developing EC. Further well-designed studies are needed to confirm these associations.

Candidate gene as well as genome-wide association studies identified several polymorphic variants to be associated with lung cancer worldwide including in India. However, contradictory results have failed to estimate the overall effect of the polymorphic variants on the disease. Textmining was conducted on PubMed following specific search strings to gather all the publications related to genetic association with lung cancer in India. Out of 211 PubMed hits only 30 studies were selected for meta-analysis following specific inclusion criteria. Heterogeneity between studies was calculated by Cochran's Q-test (P < 0.05) and heterogeneity index (I

Oral cancer etiology is complex and controlled by multi-factorial events including genetic events. Candidate gene studies, genome-wide association studies, and next-generation sequencing identified various chromosomal loci to be associated with oral cancer. There is no available review that could give us the comprehensive picture of genetic loci identified to be associated with oral cancer by candidate gene studies-based, genome-wide association studies-based, and next-generation sequencing-based approaches. A systematic literature search was performed in the PubMed database to identify the loci associated with oral cancer by exclusive candidate gene studies-based, genome-wide association studies-based, and next-generation sequencing-based study approaches. The information of loci associated with oral cancer is made online through the resource "ORNATE." Next, screening of the loci validated by candidate gene studies and next-generation sequencing approach or by two independent studies within candidate gene studies or next-generation sequencing approaches were performed. A total of 264 loci were identified to be associated with oral cancer by candidate gene studies, genome-wide association studies, and next-generation sequencing approaches. In total, 28 loci, that is, 14q32.33 (AKT1), 5q22.2 (APC), 11q22.3 (ATM), 2q33.1 (CASP8), 11q13.3 (CCND1), 16q22.1 (CDH1), 9p21.3 (CDKN2A), 1q31.1 (COX-2), 7p11.2 (EGFR), 22q13.2 (EP300), 4q35.2 (FAT1), 4q31.3 (FBXW7), 4p16.3 (FGFR3), 1p13.3 (GSTM1-GSTT1), 11q13.2 (GSTP1), 11p15.5 (H-RAS), 3p25.3 (hOGG1), 1q32.1 (IL-10), 4q13.3 (IL-8), 12p12.1 (KRAS), 12q15 (MDM2), 12q13.12 (MLL2), 9q34.3 (NOTCH1), 17p13.1 (p53), 3q26.32 (PIK3CA), 10q23.31 (PTEN), 13q14.2 (RB1), and 5q14.2 (XRCC4), were validated to be associated with oral cancer. "ORNATE" gives a snapshot of genetic loci associated with oral cancer. All 28 loci were validated to be linked to oral cancer for which further fine-mapping followed by gene-by-gene and gene-environment interaction studies is needed to confirm their involvement in modifying oral cancer.

Many studies have analyzed the association between between GSTT1 polymorphism and esophageal cancer, however, the results remained inconclusive. We therefore performed an updated meta-analysis based on Chinese individuals. PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine were searched up to December 2016. An OR with the corresponding 95% CI was used to assess the strength of the association. This meta-analysis included 12 studieswith 1246 cases and 1863 controls. Overall, GSTT1 null genotype was associated with an increased esophageal cancer risk when all studies in Chinese populations pooled into this meta-analysis. In stratified studies with geographical location, significantly increased risk was found in North China (OR = 1.45, 95%CI: 1.11-1.91) and in studies with population-based control (OR = 1.29, 95%CI: 1.07-1.55). This study suggested that GSTT1 null genotype may be potential biomarkers for esophageal cancer in China, especially in North China. Studies with larger sample sizes and wider spectrum of populations are warranted to verify this finding.

Multiple genetic and environmental factors and their interaction are believed to contribute in the pathogenesis of Nasopharyngeal Cancer (NPC). We investigate the role of Metabolic Phase I (CYPs) and Phase II (GSTs) gene polymorphisms, gene-gene and gene-environmental interaction in modulating the susceptibility to NPC in Northeast India. To determine the association of metabolic gene polymorphisms and environmental habits, 123 cases and 189 controls blood/swab samples were used for PCR and confirmed by Sanger sequencing. Analysis for GSTM1 and GSTT1 gene polymorphism was done by multiplex PCR. The T3801C in the 3'- flanking region of CYP1A1 gene was detected by PCR-RFLP method. The Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The GSTM1 null genotype alone (OR = 2.76) was significantly associated with NPC risk (P < 0.0001). The combinations of GSTM1 null and GSTT1 null genotypes also higher, 3.77 fold (P < 0.0001), risk of NPC, while GSTM1 null genotype along with CYP1A1 T3801C TC + CC genotype had 3.22 (P = 0.001) fold risk. The most remarkable risk was seen among individual carrying GSTM1 null, GSTT1 null genotypes and CYP1A1 T3801C TC + CC genotypes (OR = 5.71, P = 0.001). Further; analyses demonstrate an enhanced risk of NPC in smoked meat (OR = 5.56, P < 0.0001) and fermented fish consumers (OR = 5.73, P < 0.0001) carrying GSTM1 null genotype. An elevated risk of NPC was noted in smokers (OR = 12.67, P < 0.0001) and chewers (OR = 5.68, P < 0.0001) with GSTM1 null genotype. However, smokers had the highest risk of NPC among individuals carrying GSTT1 null genotype (OR = 4.46, P = 0.001) or CYP1A1 T3801C TC + CC genotype (OR = 7.13, P < 0.0001). The association of null genotypes and mutations of metabolic neutralizing genes along with the environmental habits (tobacco smokers and chewers, smoke meat, fermented fishes) can be used as a possible biomarker for early detection and preventive measure of NPC.

The detoxifying activity of glutathione S-transferases (GST) enzymes not only protect cells from the adverse effects of xenobiotics, but also alters the effectiveness of drugs in cancer cells, resulting in toxicity or drug resistance. In this study, we aimed to evaluate the association of GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms with treatment response among Malaysian chronic myeloid leukaemia (CML) patients who everyday undergo 400 mg of imatinib mesylate (IM) therapy. Multiplex polymerase chain reaction (multiplex-PCR) was performed to detect GSTM1 and GSTT1 polymorphisms simultaneously and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was conducted to detect the GSTP1 Ile195Val polymorphism. On evaluating the association of the variant genotype with treatment outcome, heterozygous variant (AG) and homozygous variant (GG) of GSTP1 Ile105Val showed significantly a higher risk for the development of resistance to IM with OR: 1.951 (95% CI: 1.186-3.209, P = 0.009) and OR: 3.540 (95% CI: 1.305-9.606, P = 0.013), respectively. Likewise, GSTT1 null genotype was also associated with a significantly higher risk for the development of resistance to IM with OR = 1.664 (95% CI: 1.011-2.739, P = 0.045). Our results indicate the potential usefulness of GST polymorphism genotyping in predicting the IM treatment response among CML patients.

Oral leukoplakia and erythroleukoplakia are common oral potentially malignant disorders diagnosed in the oral cavity. The specific outcome of these lesions remains to be elucidated, as their malignant transformation rate exhibits great variation. The ability to predict which of those potentially malignant lesions are likely to progress to cancer would be vital to guide their future clinical management. The present study reported two patients with tongue squamous cell carcinoma: Case study 1 was diagnosed with a simultaneous leukoplakia and case study 2 developed an erythroleukoplakia following the primary tumor treatment. Whole genome copy number alterations were analyzed using array comparative genomic hybridization. The present study determined more genomic imbalances in the tissues from leukoplakia and erythroleukoplakia compared with their respective tumors. The present study also identified in tumor and potentially malignant lesions common alterations of chromosomal regions and genes, including FBXL5, UGT2B15, UGT2B28, KANSL1, GSTT1 and DUSP22, being some of these typical aberrations described in oral cancer and others are linked to chemoradioresistance. Several putative genes associated with hallmarks of malignancy that may have an important role in predicting the progression of leukoplakia and erythroleukoplakia to squamous cell carcinoma, namely gains in BNIPL, MCL1, STAG2, CSPP1 and ZNRF3 genes were also identified.

PURPOSE: To study the potential links between genetic polymorphisms in the GSTT1, GSTM1, GSTP1 genes and the frequency of chromosomal aberrations (CAs) in lung cancer patients and healthy residents in Russian Federation.
METHODS: 200 cells in well-spread metaphase with 46 chromosomes were examined for 353 newly diagnosed lung cancer patients (males) who received medical treatment in the Kemerovo Regional Oncology Center (Kemerovo, Russian Federation), and 300 healthy males from Kemerovo, Russian Federation. The polymorphisms of the GSTM1 del and GSTT1 del genes were analysed by multiplex PCR. Genotyping of the polymorphic variants in the GSTP1 (A313G, T341C) gene was performed using Real-time PCR with competing TaqMan probes complementary to the polymorphic DNA sites. The data analysis was performed using software STATISTICA 8.0 (StatSoft Inc., USA).
RESULTS: We discovered that a GSTM1 del polymorphism increases the frequency of chromosomal damage in smoking patients with lung cancer, a general group of lung cancer patients, donors with non-small cell lung cancer and patients in the latest stages of the malignant process. The synergetic effects of occupational exposure and the malignant process can induce some modifications in the cytogenetic status in lung cancer patients harbouring the GSTM1 del polymorphism.
CONCLUSIONS: CAs in peripheral blood lymphocytes can be used as biomarkers of the early biological effects of exposure to genotoxic carcinogens and may predict future cancer incidence in several epidemiologic studies. Genetic changes in genes encoding phase II detoxification enzymes are linked to decreases in the metabolic detoxification of environmentally derived genotoxic carcinogens.

BACKGROUND: We investigated whether GSTT1 ("null" allele), GSTM1 ("null"allele), GSTP1 (A313G), RFC1 (G80A), MTHFR (C677T), TS (2R/3R) polymorphisms were associated with toxicity and survival in patients with early breast cancer (EBC) treated with adjuvant chemotherapy (CT).
METHODS: This prospective trial included patients with stage I-III BC subjected to CT with CMF or FEC regimens. PCR-RFLP was performed for MTHFR, RFC1 and GSTP1, while PCR for TS, GSTT1 and GSTM1 genes.
RESULTS: Among the 244 patients consecutively enrolled, 48.7% were treated with FEC and 51.3% with CMF. Patients with TS2R/3R genotype showed less frequently severe neutropenia (G3/G4) than those with TS2R/2R and 3R/3R genotype (p = 0.038). Patients with MTHFRCT genotype had a higher probability of developing severe neutropenia than those with MTHFR CC genotype (p = 0.043). Patients with RFC1GG or GSTT1-null genotype or their combination (GSTT1-null/RFC1GG) were significantly associated with a shorter disease free survival (DFS) (p = 0.009, p = 0.053, p = 0.003, respectively) and overall survival (OS) (p = 0.036, p = 0.015, p = 0.005, respectively). Multivariate analysis confirmed the association of RFC1GG genotype with a shorter DFS (p = 0.018) and of GSTT1-null genotype of a worse OS (p = 0.003), as well as for the combined genotypes GSTT1-null/RFC1GG, (DFS: p = 0.004 and OS: p = 0.003).
CONCLUSIONS: Our data suggest that TS2R/2R and 3R/3R or MTHFR CT genotypes have a potential role in identifying patients with greater risk of toxicity to CMF/FEC and that RFC1 GG and GSTT1-null genotypes alone or in combination could be important markers in predicting clinical outcome in EBC patients.

The influences of glutathione s-transferase P1, M1, and T1 variants on the efficacy of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients were inconsistent in previous studies. Our meta-analysis enrolled 31 publications including 5712 patients and provided more convincing and reliable conclusions. Results showed that GSTP1 IIe105Val IIe/Val and Val/Val Asian patients were more likely to have better response rates compared to IIe/IIe patients (odds ratio (OR) = 1.592, 95% confidence intervals (CIs), 1.087-2.332, P = 0.017). The Asian patients bearing the favorable GSTM1 null genotype were more likely to have better response rates to platinum-based chemotherapy compared to those patients with the unfavorable GSTM1 present genotype (OR = 1.493 (1.192-1.870), P < 0.001). Caucasian lung cancer patients bearing GSTT1 null genotype might be more closely associated with shorter survival time and higher risks of death than the GSTT1 present patients (hazard ratio (HR) = 1.423, CI = 1.084-1.869, P = 0.011). Our meta-analysis suggested that the GSTP1 IIe105Val, GSTM1 and GSTT1 null variants might be predictive factors for the efficacy of platinum-based chemotherapy to NSCLC patients. The use of GSTP1 IIe105Val, GSTM1 and GSTT1 null polymorphisms as predictive factors of efficacy of personalized platinum-based chemotherapy to NSCLC patients requires further verification with multi-center, multi-ethnic and large-sample-size pharmacogenetic studies.