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Análise dos genes GSTM1 e GSTT1 em pacientes com cancer de cabe?a e pesco?o
Leme, Cássia Veridiana Dourado;Raposo, Luis Sérgio;Ruiz, Mariangela Torreglosa;Biselli, Joice Matos;Galbiatti, Ana Lívia Silva;Maniglia, José Victor;Pavarino-Bertelli, érika Cristina;Goloni-Bertollo, Eny Maria;
Revista da Associa??o Médica Brasileira , 2010, DOI: 10.1590/S0104-42302010000300013
Abstract: objective: to establish the clinical and demographic profile and identify risk factors among patients with head and neck cancer and relate them to the polymorphism of gstt1 and gstm1. methods: one hundred patients with head and neck cancer and 100 control group individuals without history of neoplasm were analyzed. . the molecular analysis were made by multiplex polymerase chain reaction. for statistical analysis, data were tabulated and compared by the fishera€?s exact test, the chi-square test and multiple logistic regression were also used. results: there was prevalence of smokers (or = 5.32, ci 95% ci = 2.04-13.86 p = 0.0006), alcohol drinkers (or = 5.04, ci 95% = 2.19-11.59 p = 0.0001) in head and neck cancer patients . the gstt1 null genotype was found in 47% of the patient and 41% of the control group (or = 0.67; ci 95%= 0.34-1.35; p = 0.2648). likewise , the gstm1 null genotype was found in 66% of the patient and 75% of the control group (or = 2.25; ci 95%= 1.05 - 4.84; p = 0.0368). the combined gstt1 and gstm1 gene null genotype shown association between gstm1*0/gstt1 and occurrence of head and neck carcinoma (or = 7.64; ci 95%= 1.72-34.04; p = 0.0076). analysis of clinical-pathological features showed association between gstt1 null genotype and larynx, the inverse relation between this genotype and pharynx. conclusion: in our study it was possible to establish association between gstm1 null genotypes and head and neck cancer.
Avalia??o da influência da nulidade dos genótipos GSTT1 e GSTM1 na carcinogênese em cabe?a e pesco?o
Goloni-Bertollo, Eny Maria;Biselli, Joice Matos;Corrêa, Léa Carolina deLima;Maníglia, José Victor;Rossit, Andréa Regina Baptista;Ruiz, Mariangela Torreglosa;Pavarino-Bertelli, érika Cristina;
Revista da Associa??o Médica Brasileira , 2006, DOI: 10.1590/S0104-42302006000500028
Abstract: background: to evaluate the influence of gstm1 and gstt1 null genotypes in head and neck carcinogenesis. methods: the frequencies of gstm1 and gstt1 null genotypes were evaluated by multiplex polymerase chain reaction (pcr) in 45 patients with head and neck squamous cell carcinoma and in 45 control group individuals. both groups were composed of smokers paired by gender, age and race. results: the gstt1 null genotype was found in 24.4% of the patients and 17.7% of the control group (p= 0.606), while 44.4% of the patients and 48.8% of the control group were bearers of the gstm1 null genotype (p=0.832). no associations between gstt1 and gstmi null genotypes and primary tumor sites were found. conclusion: in our study, it was impossible to establish the influence of the gstt1 and gstm1 null genotypes in head and neck carcinogenesis.
Intera??o entre consumo alimentar e polimorfismos da GSTM1 e GSTT1 no risco para o cancer de cabe?a e pesco?o: estudo caso-controle em S?o Paulo, Brasil
Marchioni, Dirce Maria Lobo;Gattás, Gilka Jorge Figaro;Curioni, Otavio A.;Carvalho, Marcos Brasilino de;
Cadernos de Saúde Pública , 2011, DOI: 10.1590/S0102-311X2011000200019
Abstract: a hospital-based case-control study was conducted to investigate the potential interaction between dietary factors and polymorphisms in phase ii metabolic enzymes gstm1 and gstt1, associated with head and neck cancer risk. the study included 103 histologically confirmed incident cases and 101 controls. food intake was estimated with a validated food frequency questionnaire. the gene polymorphisms were evaluated by pcr. increased risk was observed in the highest tertile of beef consumption in the presence of the gstm1 (or = 10.79; 95%ci: 2.17-53.64) and gstt1 null alleles (or = 3.41; 95%ci: 0.43-27.21). assessment of dietary intake considering the ratio between animal product and vegetable consumption showed or = 2.35 (95%ci: 0.27-19.85) in the intermediate tertile and or = 3.36 (95%ci: 0.41-27.03) in the highest tertile. the results suggest a possible interaction between meat intake and gstm1/gstt1 polymorphisms in modulating the risk of head and neck cancer, influenced by vegetable consumption.
Polimorfismos do gene da interleucina-13 nas posi es -1055 C/T e +2044 G/A em pacientes com carcinoma espinocelular de cabe a e pesco o Interleukin-13 gene polymorphisms at -1055 C/T and +2044 G/A positions in patients with squamous cell carcinoma of head and neck  [cached]
Bijan Khademi,Seyed Basir Hashemi,Abbass Ghaderi,Ali Shahrestani
Brazilian Journal of Otorhinolaryngology , 2012, DOI: 10.5935/1808-8694.20120010
Abstract: O carcinoma espinocelular (CEC) é a neoplasia mais comum do trato aerodigestivo superior. A interleucina-13 (IL-13) é uma citocina imunorreguladora com polimorfismos relatados para seu gene associados com a mesma doen a, especialmente asma e alergia. O presente estudo investigou se os polimorfismos do gene da IL-13 (posi es 1055C/T no gene promotor da 1L-13 e +2044G/T exon 4) podem distinguir os pacientes com CEC de cabe a e pesco o de controles saudáveis. MéTODO: O estudo analisou pacientes com CEC de cabe a e pesco o (n = 137) pareados por idade e sexo com um grupo de controles saudáveis (n = 127). A genotipagem do polimorfismo do gene da IL-13 foi executada pelo método de polimorfismo no comprimento de fragmentos de restri o baseado em rea o em cadeia da polimerase. RESULTADOS: N o foram identificadas diferen as estatisticamente significativas nas frequências dos genótipos e alelos entre pacientes e controles em ambas as posi es (p = 0,16). Além disso, n o foi observada associa o entre os genótipos investigados e outros fatores prognósticos, como idade, sexo, localiza o do tumor primário, tamanho do tumor e tabagismo. CONCLUS O: O presente estudo sugere que n o há associa o entre os polimorfismos do gene da IL-13 (nas posi es -1055C/T e +2044GI A) e suscetibilidade dos pacientes a CEC de cabe a e pesco o. Squamous cell carcinoma (SCC) is the most common malignancy that involves the upper aerodigestive tract. Interleukin-13 (IL-13) is an immunoregulatory cytokine that has been reported to have some polymorphisms in it gene associated with same disease especially asthma and allergy. The present study aimed to investigate whether the polymorphisms of IL-13 gene (at positions of 1055C/T in the promoter of1L-13 gene and +2044G/T exon-4) differ in patients with head and neck SCC from healthy controls. METHODS: This study was investigated in patient with head and neck SCC (n = 137) and age- and sex-matched healthy controls (n = 127). Genotyping of IL-13 gene polymorphism was performed using polymerase chain reaction-based restriction fragment length polymorphism method. RESULTS: No statistically significant differences were found in the frequencies of genotypes and alleles between patients and control group at both sites (p = 0.16). In addition, no association was observed between investigated genotypes and other potential prognostic factors such as age, sex, primary tumor site, tumor size and smoking. CONCLUSION: This study suggests that there is no association between IL-13 gene polymorphisms (at position -1055C/T and +2044GI A) and susceptibility
Distribution of glutathione S-transferase GSTM1 and GSTT1 null phenotypes in Brazilian Amerindians
Klautau-Guimar?es, Maria de Nazaré;Hiragi, Cássia de Oliveira;D'Ascen??o, Renata Ferreira;Oliveira, Silviene Fabiana;Grisolia, Cesar Koppe;Hatagima, Ana;Ferrari, íris;
Genetics and Molecular Biology , 2005, DOI: 10.1590/S1415-47572005000100005
Abstract: the distribution of glutathione s-transferase (gst) gstm1 and gstt1 null phenotype frequencies in two brazilian amerindian tribes, the munduruku tribe from miss?o cururu village (79 individuals) and the kayabi tribe (41 individuals), was analyzed by polymerase chain reaction (pcr) amplification. the gst null phenotype frequencies for the munduruku sample were 0% for gstm1 and 27% for gstt1 while for the kayabi sample the null phenotype frequencies were 27% for gstm1 and 29% for gstt1. this is the first report of the absence of the gstm1 null phenotype in any ethnic group.
Association between GSTM1 and GSTT1 Allelic Variants and Head and Neck Squamous Cell Cancinoma  [PDF]
Yang Zhang, Yuanyuan Ni, Hao Zhang, Yongchu Pan, Junqing Ma, Lin Wang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047579
Abstract: Backgrounds GSTM1 and GSTT1 are involved in the detoxification of carcinogens such as smoking by-products, and polymorphisms in these two genes with a result of loss of enzyme activity may increase risk of carcinogenesis. Although many epidemiological studies have investigated the association between GSTM1 or GSTT1 null genotype and head and neck squamous cell carcinoma (HNSCC), the results remain conflicting. To elucidate the overall association of GSTM1, GSTT1 and HNSCC, we included all available studies and performed this meta-analysis. Methodology/Principal Findings A dataset including 42 articles for GSTM1, 32 articles for GSTT1, and 15 articles for GSTM1 and GSTT1 in combination were identified by a search in PubMed. Associations beween HNSCC and polymorphisms of GSTM1 and GSTT1 alone and in combination were analysed by software RevMan 5.1. Stratification analysis on ethnicity and smoking status, sensitivity analysis, heterogeneity among studies and their publication bias were also tested. Association was found in overall analysis between HNSCC and GSTM1 and GSTT1 null genotype. Stratified by ethnicity, we found increased risks of HNSCC in carriers with GSTM1 null genotype in Asian, GSTT1 null genotype in South American, and dual null genotype in European and Asian. When stratified by smoking, a more significant association of GSTM1 null genotype with HNSCC risk was observed in smokers. Conclusions/Significance This meta-analysis presented additional evidence of the association between GSTM1 and GSTT1 polymorphisms and HNSCC risk.
Association between GSTM1 and GSTT1 polymorphisms and susceptibility to methamphetamine dependence
Mohammad Rashid Khalighinasab, Khyber Saify, Mostafa Saadat
Molecular Biology Research Communications , 2015,
Abstract: Glutathione S-transferases (GSTs; EC: 2.5.1.18) are ubiquitous multifunctional enzymes, which play a key role in cellular detoxification. Functional genetic polymorphisms in genes encoding GSTM1 (a member of GST class mu; OMIM: 138350), and GSTT1 (a member of GST class theta; OMIM: 600436) have been well defined. The functional null alleles of GSTM1 and GSTT1 represent deletions of GSTM1 and GSTT1 genes, respectively. The aim of the present study is to investigate the association between GSTM1 and GSTT1 polymorphisms and methamphetamine dependence. The present population-based case-control study was performed in Shiraz (southern Iran). In total, 52 methamphetamine dependence (11 females, 41 males) and 635 healthy controls (110 females, 525 males) were included in this study. The genotypes of GSTM1 and GSTT1 polymorphisms were determined by PCR. Neither GSTM1 (OR=0.92, 95% CI: 0.52-1.61, P=0.771) nor GSTT1 (OR=0.71, 95% CI: 0.33-1.54, P=0.381) null genotypes were significantly associated with risk of methamphetamine dependence. It should be noted that although there was no association between the GSTM1 null genotype and risk of methamphetamine dependence, in both genders, there was significant interaction between gender and GSTM1 polymorphism (P=0.029). The combination genotypes of the GSTM1 and GSTT1 polymorphisms revealed that the genotypes of these two polymorphisms had no additive effect in relation to the susceptibility to methamphetamine dependence. The present study revealed that genetic polymorphisms of GSTT1 and GSTM1 are not risk factors for methamphetamine dependence.
No association between GSTM1 and GSTT1 genetic polymorphisms and susceptibility to opium sap dependence
Khyber Saify, Mohammad Rashid Khalighinasab, Mostafa Saadat
Molecular Biology Research Communications , 2016,
Abstract: Glutathione S-transferases (GSTs; EC: 2.5.1.18) are a ubiquitous family of eukaryotic and prokaryotic phase II metabolic isozymes. Genes encoding GSTM1 (OMIM: 138350), and GSTT1 (OMIM: 600436) are members of class mu and theta, respectively. The most common polymorphism in the GSTM1 is a deletion of the whole GSTM1 gene with a lack of enzyme activity. A homozygous deletion in the GSTT1 has also been reported (null genotypes of GSTT1). The aim of the present study was to investigate the association between GSTM1 and GSTT1 polymorphisms and risk of dependency to opium sap. The present study was performed in Shiraz (southern Iran). In total, 71 males dependent to opium sap and 590 healthy males (as a control group) were included in this study. The genotypes of GSTM1 and GSTT1 polymorphisms were determined by PCR. Our data indicate that neither GSTM1 (OR=0.78, 95% CI: 0.47-1.27, P=0.325) nor GSTT1 (OR=1.25, 95% CI: 0.70-2.21, P=0.442) null genotypes significantly associated with the risk of opium sap dependence. There is no additive effect of the null genotypes of GSTT1 and GSTM1 in relation to the risk of dependency to opium sap. The present study indicated that the null genotypes of GSTT1 and GSTM1 are not risk factor for opium sap dependence.
海南汉族健康人群GSTT1、GSTM1基因多态性分析  [PDF]
蔡群芳,邬强
中国公共卫生 , 2013, DOI: 10.11847/zgggws2013-29-06-42
Abstract: ?目的探讨海南汉族人群谷胱甘肽S转移酶GSTM1基因和GSTT1基因多态性分布情况。方法应用多重PCR扩增方法检测147名汉族健康人群GSTM1基因型和GSTT1基因型。结果147名海南汉族人群中,GSTM1-基因型频率为56.5%(83/147),GSTT1-基因型频率为40.8%(60/147),GSTM1-/GSTT1-基因型频率为25.2%(37/147),2基因在正常人群中分布与年龄、性别无关,且相互独立无关联。结论海南汉族健康人群GSTM1基因和GSTT1基因多态性与不同地区正常人群之间存在一定差异性(P<0.01)。
No contribution of GSTM1 and GSTT1 null genotypes to the risk of neutropenia due to benzene exposure in Southeastern Brazil
Lima, Carmen Silvia Passos;Louren?o, Gustavo Jacob;Lorand-Metze, Irene;Nascimento, Helvia;Saad, Sara Teresinha Ollala;Costa, Fernando Ferreira;
Genetics and Molecular Biology , 2009, DOI: 10.1590/S1415-47572009005000067
Abstract: exposure to benzene has been associated with haematological diseases such as neutropenia (neb) and acute myeloid leukaemia (aml). we tested whether the null genotypes of the gstm1 and gstt1 genes, involved in benzene inactivation, altered the risk for neb in southeastern brazil. genomic dna from 55 neb patients and 330 controls was analysed by multiplex-polymerase chain reaction. the frequency of the gstm1, gstt1 and combined null genotypes was similar in patients and controls (gstm1, 27.3% vs. 38.8%, p = 0.16; gstt1, 25.5% vs. 19.7%, p = 0.24; gstm1/gstt1, 12.7% vs. 6.7%, p = 0.26; respectively). the distribution of genotype classes in neb patients was similar to normal controls, suggesting that gstm1 and gstt1 null genotypes make no specific contribution to the risk of neb. as the gstm1 and gstt1 null genotypes were previously associated with increased risk for aml in brazil and elsewhere, we hypothesise that different thresholds of chemical exposure relative to distinct gstm1 and gstt1 genotypes may determine whether aml or neb manifests in benzene exposed individuals from southeastern brazil. although indicative, our results still require support by prospective and large scale epidemiological studies, with rigorous assessment of daily chemical exposures and control of the possible contribution of other polymorphic genes involved in benzene metabolism.
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