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GSTM1 null polymorphism – a possible key for oral carcinogenesis
Tanwar Renu,Asha R. Iyengar,Kekkeri Sitaram Nagesh
RSBO , 2013,
Abstract: Introduction: Carcinogenesis is a multistep process and individual risk to development of cancer depends not only on environmental factors or extrinsic exposure to carcinogens but also on genetic susceptibility of an individual. In head and neck cancer, tobacco exposure and alcohol consumption are predominantly the most significant external factors for tumor formation. Individual’s susceptibility to cancer may be partly explained by variability in enzymatic activities of metabolic genes. Mutations in genes concerned with production of enzymes for metabolism of tobacco products may lead to increased risk of carcinogenesis with respect to oral mucosa. Therefore variations in the expression of these genes due to heritable genetic polymorphisms might modulate the process of carcinogenesis by altering the exposure levels of tobacco derived carcinogens. Objective: This non systematic review summarizes current data available on the role of environment gene interaction in form of GSTM1 null polymorphism and oral carcinogenesis. Literature review: Relevant data was selected in order to summarize the studies conducted on GSTM1 null polymorphism and oral cancer. Conclusion: Relationship between GSTM1 null polymorphism in oral cancer needs to be established to confirm the role of environment gene interaction in oral carcinogenesis.
The relationship between genetic polymorphism of GSTM1 and the outcome of chemotherapy in Chinese patients with primary lung cancer  [cached]
Weiying LI,Yanfei GU,Baitang LAI,Hui WANG
Chinese Journal of Lung Cancer , 2008,
Abstract: Background and objective GSTM1 takes part in the metabolism of environmental pollutants such as benzopyrene other polycyclic aromatic hydrocarbons and anticancer drugs and so on. The study aims to investigate the relationship between the gene polymorphism of GSTM1 and chemotherapy as well as to study the effect to survival of Chinese patients with lung cancer. Methods The genotypes of GSTM1 were examined with polymerase chain reaction in 137 primary lung cancer patients accepted chemotherapy. Results GSTM1 -null genotype frequency was 58.4%(80?137). The frequency of non-null GSTM1 genotype was 41.6%(57?137). The frequency of GSTM1-null genotype was 69.05%(58?84) in the response group of chemotherapy and 41.51%(22?53) in the non-response group of chemotherapy. They were significantly different (P=0.001). In the patients with platinum chemotherapy, the frequency of GSTM1-null genotype was 65.43%(53?81) in the response group of chemotherapy and 42%(21?50) in the non-response group. There werestastically differences in them (P=0.0025). For the advanced cases, GSTM1 -null genotype frequency was 70.13% (54 ? 77) in the response group of chemotherapy, 41.51% (22?53) in the non-response group of chemotherapy respectively and they were significantly different(P=0.001). When the chemotherapy was effective, the survival time of patients in squamous carcinoma and small cell carcinoma with non-null GSTM1 genotype (the median survival times were 42 months and 14 months respectively) were longer than those with null GSTM1 genotype (the median survival times were 6 months and 7 months respectively)(P0.05. When chemotherapy was not effective, the median survival time were not significantly different (P>0.05). Conclusions The effect of chemotherapy of GSTM1-null genotype patients was better than that of GSTM1-postive genotype patients. The chemotherapy effect of the cases with null GSTM1 type was better than those with non-null GSTM1 type when the patients accepted platinum chemotherapy. When the chemotherapy was effective, the survival time may be related to the histological types and GSTM1 genotypes.
Association between GSTM1 Genetic Polymorphism and Lung Cancer Risk by SYBR Green I Real-time PCR Assay  [PDF]
Dejie ZHENG,Feng HUA,Chaorong MEI,Haisu WAN
Chinese Journal of Lung Cancer , 2010,
Abstract: Background and objective Glutathione S-transferase M1 (GSTM1) is an important phase II metabolic enzyme gene which involves metabolism of various carcinogens in human body. Many studies showed that GSTM1 genetic polymorphism was associated with lung cancer risk. The aim of this study is to investigate the relationship between GSTM1 genetic polymorphism and lung cancer risk among Han nationality population in Tianjin district. Methods GSTM1 genetic polymorphism was detected by melting curve analysis of SYBR green I real-time PCR assay. Two hundred and sixty-five histological confirmed lung cancer patients and 307 health controls were recruited in this case-control study and the relationship between GSTM1 genetic polymorphism and lung cancer risk was investigated. Results (1) The frequency of the GSTM1(-) in lung cancer and control groups was 56.6% and 57.0% respectively, and no significant difference was found between the distribution of the GSTM1(-) genotype in the two groups (χ2=0.831, P=0.362). (2) When considered the GSTM1(+) genotype as reference, there was no overall statistically increased lung cancer risk for carriers with the GSTM1(-) genotype adjusted by age, gender and smoking status (OR=0.840, 95%CI: 0.578-1.221, P=0.362). (3) The frequency of the GSTM1(-) genotype for squamous cell carcinoma, adenocarcinoma, SCLC and other histological types was 65.8%, 48.5%, 47.8% and 52.2% respectively, compared with the control group, no statistically increased lung cancer risk was observed (P>0.05). Conclusion No evidence is found between GSTM1 genetic polymorphism and lung cancer risk among Han nationality population in Tianjin district.
Is There a Relation Between Testosterone or Estradiol Levels in Seminal Plasma and GSTM1 Polymorphism in Infertile Patients?  [cached]
?lhan Onaran,Birsen Aydemir,Ali R?za K?z?ler,Bülent Al?c?
Erciyes Medical Journal , 2008,
Abstract: Purpose: Glutathione S-transferase M1 (GSTM1) enzyme has been suggested to serve as a steroid-binding protein by its ability to bind to testosterone and estradiol, two important hormones in seminiferous tubule that are essential for spermatogenesis. We investigated whether GSTM1 polymorphism was associated with blood and seminal plasma levels of testosterone and estradiol in subfertile and control subjects.Material and Methods: The levels of total estradiol and testosterone were measured by using an electrochemiluminescence immunoassay in serum and seminal plasma from 103 individuals including 62 subfertile patients. GSTM1 polymorphism was examined using polymerase chain reaction.Results: The estradiol and testosterone levels in seminal plasma were not significantly different in the control and subfertile subjects. No role for GSTM1 enzyme as a steroid-binding protein seemed likely as there was also no significant difference in seminal plasma estradiol and testosterone levels according to GSTM1 genotype. Using Spearman rank correlation analysis, significant positive correlations were found between seminal estradiol and serum estradiol in infertile males, and between seminal testosterone and serum testosterone in fertile males, independent of GSTM1 genotype.Conclusion: The results suggest that GSTM1 polymorphism is not a genetic risk factor for seminal estradiol and testosterone levels in infertile males.
No association between the GSTM1 and GSTT1 polymorphism and endometrial cancer risk: A meta-analysi  [PDF]
Marce-Amara Kpoghomou, Fatch W. Kalembo, Joella Eldie Soatiana
Open Journal of Obstetrics and Gynecology (OJOG) , 2013, DOI: 10.4236/ojog.2013.34072
Abstract:

Purpose: A number of case-control studies have been conducted to investigate the association of glutathione S-transferase (GST) genetic polymorphisms and endometrial carcinoma risk. However, these studies have yielded contradictory results. We therefore performed a meta-analysis to derive a more precise estimation of the association between polymorphisms on GSTM1, GSTT1 and endometrial carcinoma. Methods: Identification of relevant studies was carried out through a search in the following databases Medline, EMbase andChinaNational Knowledge International (CNKI) up to March. 2013. All case-control studies that investigated the association between GS-TM1 and GSTT1 gene polymorphisms and risk of endometrial cancer were included in the study. The pooled odds ratio (OR) was used for analyses of results and the corresponding 95% confidence intervals (CI) were estimated. Result: Six published case-control studies of association between the GSTM1 and GSTT1 polymorphism and endometrial cancer risk covering 3558 subjects were included in the metaanalysis, but the results indicated that the null genotypes of GSTM1 and GSTT1 polymorphisms were not associated with a significantly increased risk of endometrial cancer (for GSTM1: OR = 0.99; 95% CI, 0.86 - 1.4; for GSTT1: OR = 0.96; 95% CI, 0.80 - 1.14, respectively). Conclusion: This meta-analysis suggests that GSTM1 and GSTT1 polymorphism may not be associated with increased risk of endometrial cancer. To validate the association between polymorphism and endometrial cancer, further studies with larger numbers of participants worldwide are needed.

Maternal Smoking,GSTM1 and GSTT1 Polymorphism and Susceptibility to Adverse Pregnancy Outcomes  [PDF]
Regina Grazuleviciene,Asta Danileviciute,Ruta Nadisauskiene,Jone Vencloviene
International Journal of Environmental Research and Public Health , 2009, DOI: 10.3390/ijerph6031282
Abstract: The objective of the study was to investigate the association between maternal smoking, GSTM1, GSTT1 polymorphism, low birth weight (LBW, < 2,500 g) and intra-uterine growth restriction (IUGR, < 2,500 g and gestation ≥ 37 weeks) risk. Within a prospective cohort study in Kaunas (Lithuania), a nested case-control study on LBW and IUGR occurrence among 646women with genotyping of GSTT1 and GSTM1 polymorphisms who delivered live singletons was conducted. Multivariate logistic regression analysis was used to study the association of maternal smoking and polymorphism in two genes metabolizing xenobiotics. Without consideration of genotype, light-smoking (mean 4.8 cigarettes/day) during pregnancy was associated with a small increase in LBW risk, adjusted OR 1.21; 95% CI 0.44 – 3.31. The corresponding odds for IUGR risk was 1.57; 95% CI 0.45 – 5.55. The findings suggested the greater LBW risk among light-smoking mothers with the GSTM1-null genotype (OR 1.91; 95% CI 0.43 – 8.47) compared to those with GSTM1-present genotype (OR 1.11; 95% CI 0.26 – 4.47). When both GSTM1 and GSTT1 genotypes were considered, the synergistic effect was found among smoking mothers: GSTT1-present and GSTM1-null genotype OR for LBW was 3.31; 95% CI 0.60-18.4 and that for IUGR was 2.47; 95% CI 0.31 – 13.1. However there was no statistically significant interaction between maternal smoking, GSTT1- present and GSTM1-null genotypes for LBW (OR 1.45; 95% CI 0.22 – 10.1, p = 0.66) and for IUGR (OR 1.10; 95% CI 0.10 – 12.6, p = 0.93).The results of this study suggested that smoking, even at a low-level, ought to be considered a potential risk factor for adverse birth outcomes and that genetic polymorphism may contribute to individual variation in tobacco smoke response.
The Role of GSTM1 and GSTT1 Polymorphism in Patients with Renal Cell Carcinoma
Vesna ori , Marija Plje a-Ercegovac, , Marija Mati , , Biljana Krivi , Sonja uvakov, , Cane Tuli , , Jasmina Mimi -Oka, , Tatjana Simi
Journal of Medical Biochemistry , 2010, DOI: 10.2478/v10011-010-0025-8
Abstract: Members of the glutathione S-transferase (GST) superfamily exhibit polymorphic expression. GSTs are investigated as biomarkers of risk for various cancers, including renal cell carcinoma (RCC). The aim of this study was to test the association between GSTM1 and GSTT1 polymorphism and susceptibility to RCC, independently or in conjunction with known risk factors. Genomic DNA was isolated from 182 controls and 76 patients with RCC. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. Data obtained were analyzed with respect to RCC risk factors including smoking and occupational exposure. The frequency of GSTM1-null genotype was higher in patients with RCC (60.5%) compared to controls (47.2%). GSTT1-null genotype was found in 28.6% controls and 27.6% of cases. GSTM1-null individuals exhibit 1.9-fold increased risk of RCC (95% CI: 1.06-3.33). The presence of GSTT1 active genotype was associated with increased risk of RCC in occupationally exposed subjects when unexposed GSTT1-null subjects were used as a comparison group (OR: 2.48; 95% CI: 1.05-5.86). No association was found between the inactive form of GSTM1 and GSTT1 and smoking in RCC patients. In a Serbian cohort of patients, the presence of a GSTM1 active genotype is protective against RCC, whereas a GSTT1 active genotype increases RCC risk in occupationally exposed subjects.
Genetic polymorphism of GSTM1 and GSTP1 in lung cancer in Egypt
Maggie M. Ramzy,Mohei El-Din M. Solliman,Hany A. Abdel-Hafiz,Randa Salah
International Journal of Collaborative Research on Internal Medicine & Public Health , 2011,
Abstract: Background: Lung cancer (LC) is the most common cause of cancer-related mortality; it is one of the most important common diseases with complicate, multi-factorial etiology, including interactions between genetic makeup and environmental factors. Individuals may differ in their susceptibility to environmental risk factors. This difference of susceptibility may result from inherited polymorphisms in various genes controlling carcinogen metabolism, repair of DNA damage and cell cycle.Objectives: Glutathione S-transferase (GST) plays a key role in detoxification of carcinogens present in tobacco smoke and consequently polymorphisms in this gene may confer susceptibility to many types of cancer such as lung cancer. In the current study the effect of GSTM1 and GSTP1 polymorphism on the development of lung cancer among Egyptian patients was investigated.Methods: The GSTM1 was analyzed using multiplex polymerase chain reaction (PCR) while polymorphism of GSTP1 was analyzed using RFLP. Results: It was found that there is no significant difference (p value = 0.8) in GSTM1 genotype distribution between control and lung cancer cases as it was absent in 33.3% in control and 31.25% in patients. While GSTP1 single nucleotide polymorphism (SNP) encoding A313G base change increases the susceptibility for lung cancer especially among smokers as odds ratio was 5 in case of smokers carry ile/val or val/val genotypes. Also, combination of GSTP1 and GSTM1 polymorphism increases the risk for lung cancer. Our data may provide additional information to the understanding of the molecular mechanism and individual susceptibility to lung cancer in Egypt.
Polymorphism in CYP17, GSTM1 and the progesterone receptor genes and its relationship with mammographic density
Chambo, D.;Kemp, C.;Costa, A.M.M.;Souza, N.C.N.;Guerreiro da Silva, I.D.C.;
Brazilian Journal of Medical and Biological Research , 2009, DOI: 10.1590/S0100-879X2009000400003
Abstract: radiologic breast density is one of the predictive factors for breast cancer and the extent of the density is directly related to postmenopause. however, some patients have dense breasts even during postmenopause. this condition may be explained by the genes that codify for the proteins involved in the biosynthesis, as well as the activity and metabolism of steroid hormones. they are polymorphic, which could explain the variations of individual hormones and, consequently, breast density. the constant need to find markers that may assist in the primary prevention of breast cancer as well as in selecting high risk patients motived this study. we determined the influence of genetic polymorphism of cyp17 (cytochrome p450c17, the gene involved in steroid hormone biosynthesis), gstm1 (glutathione s-transferase m1, an enzyme involved in estrogen metabolism) and progins (progesterone receptor), for association with high breast density. one hundred and twenty-three postmenopausal patients who were not on hormone therapy and had no clinical or mammographic breast alterations were included in the present study. the results of this study reveal that there was no association between dense breasts and cyp17 or gstm1. there was a trend, which was not statistically significant (p = 0.084), towards the association between progins polymorphism and dense breasts. however, multivariate logistic regression showed that wild-type progins and mutated cyp17, taken together, resulted in a 4.87 times higher chance of having dense breasts (p = 0.030). in conclusion, in the present study, we were able to identify an association among polymorphisms, involved in estradiol biosyntheses as well as progesterone response, and radiological mammary density.
CYP1A1 Gene and GSTM1 Gene Polymorphism and the Combined Effects and Risk of Lung Cancer: A meta-analysis  [cached]
Cheng LI,Zhihua YIN,Baosen ZHOU
Chinese Journal of Lung Cancer , 2011, DOI: 10.3779/j.issn.1009-3419.2011.08.05
Abstract: Background and objective Cytochrome P450A1 (CYP1A1) gene and glutathione S-transferase M1 (GSTM1) gene both have single nucleotide polymorphisms and effects on lung cancer. Currently, however, the risk of lung cancer due to the CYP1A1 and GSTM1 genes has no clear evidence. In this present study, we propose to research the combined effects of CYP1A1 gene and GSTM1 gene polymorphism and their risks to lung cancer. Methods We conducted the study at different research areas and using various database, including PubMed, Embase, China Biology Medicine (CBM) and China National Knowledge Infrastructure (CNKI) last March 31, 2011. We calculated the adjusted odds ratio (OR) and 95% confidence interval (CI) for lung cancer in each study. Using STATA 10, a statistical program, we summarized the calculated estimates for the adjusted ORs and performed a meta-analysis.Results The meta-analysis includes 15 research studies. The CYP1A1 IIe/Val genotype which carries a homozygous mutant type has a higher chance of risk to lung cancer than that which carries a homozygous mutant type and a heterozygous type when the GSTM1 carries a null genotype. As a result, OR was 3.18 (95%CI: 1.27-7.98), 1.45 (95%CI: 1.08-1.94), respectively. Meanwhile, the same conclusion was obtained for the CYP1A1 MspI genotype. The overall OR was 1.90 (95%CI: 1.00-3.58), 1.57 (95%CI: 1.23-2.00), respectively. Conclusion We discovered through our meta-analysis that the combined effects of CYP1A1 gene and GSTM1 gene polymorphism are significantly associated with an increased risk to lung cancer. We also found that homozygous mutant genotype of CYP1A1 has a higher chance of risk to lung cancer than the homozygous or heterozygous genotype.
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