Glutathione S-transferase genetic polymorphisms and fluoride-induced reproductive toxicity in men with idiopathic infertility / 亚洲男科学杂志(英文版)

Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.

Polymorphisms of the GSTT1 and GSTM1 genes in polycystic ovary syndrome

SUMMARY BACKGROUND: This study aimed to investigate the deletion polymorphisms of the genes of the glutathione S-transferase family GSTT1 and GSTM1 in patients with Polycystic Ovarian Syndrome (PCOS), comparing them with a control population. METHODS: Blood was collected from 219 women (110 with PCOS and 109 controls) and genomic DNA was extracted. For the analysis of polymorphisms, the technique used was multiplex PCR. In the statistical analysis, the chi-square test and multiple logistic regression were used. RESULTS: There is no association between the GSTM1 null and GSTT1 null genotypes with PCOS when analyzed separately (P = 0.616 and P = 0.188). The analysis of the combined genotypes showed differences between the groups (P < 0.05), evidencing that the genotypic combination GSTT1 positive and GSTM1 negative is more frequent among patients. In the multivariate analysis, smoking was more frequent in the control group (OR = 0.22; 95% CI - 0.87-0.57; P = 0.002) while the presence of a family history of PCOS (OR = 2, 96; 95% CI - 1.54-5.68; P = 0.001) was more frequent in women with PCOS. CONCLUSIONS: In the studied sample, the deletion polymorphisms of the GSTT1 and GSTM1 genes isolated are not associated with PCOS, but in combination, they may be implicated in the etiology of the condition.

RESUMO OBJETIVO: Este estudo teve como objetivo investigar os polimorfismos de deleção dos genes da família glutationa S-transferase GSTT1 e GSTM1 em pacientes com síndrome dos ovários policísticos (SOP), comparando-as com uma população controle. MÉTODOS: Foi colhido sangue de 219 mulheres (110 com SOP e 109 controles) e extraído o DNA genômico. Para análise dos polimorfismos, a técnica empregada foi PCR multiplex. Na análise estatística foi utilizado o teste do qui-quadrado e regressão logística múltipla. RESULTADOS: Não há associação dos genótipos GSTM1 nulo e GSTT1 nulo com SOP quando analisados isoladamente (p=0,616 e p=0,188). A análise dos genótipos combinados mostrou diferenças entre os grupos (p<0,05), evidenciando que a combinação genotípica GSTT1 positivo e GSTM1 negativo é mais frequente entre as pacientes. Na análise multivariada, o hábito tabagista foi mais frequente no grupo controle (OR=0,22; IC 95% - 0,87-0,57; p=0,002), enquanto que a presença do histórico de SOP familiar (OR=2,96; IC 95% - 1,54-5,68; p=0,001) foi mais frequente nas mulheres com SOP. CONCLUSÕES: Na casuística estudada, os polimorfismos de deleção dos genes GSTT1 e GSTM1 isolados não estão associados a SOP, mas em combinação podem estar implicados na etiologia da condição.

Análise comparativa do polimorfismo genético da glutationa transferase, do Helicobacter pylori e do vírus Epstein-Barr entre a área do tumor e as margens de ressecção proximal e distal do câncer gástrico / Comparative analysis of glutathione transferase genetic polymorphism, Helicobacter pylori and Epstein-Barr virus between the tumor area and the proximal and distal resection margins of gastric cancer

RESUMO Objetivo: comparar o polimorfismo dos genes Glutationa S-transferase teta 1 (GSTT1) e Glutationa S-transferase mu 1 (GSTM1) da área do tumor com as margens proximal e distal de espécimes de estômago ressecados de pacientes com câncer gástrico, e investigar a presença do DNA do vírus Epstein-Barr (EBV) e Helicobacter pylori. Métodos: coletamos prospectivamente amostras teciduais da área do tumor e das margens de ressecção proximal e distal dos estômagos de dez pacientes com adenocarcinoma gástrico submetidos à gastrectomia com linfadenectomia D2 e submetemos esses espécimes à extração de DNA. Comparamos a área do tumor com as margens proximal e distal dos estômagos ressecados para o polimorfismo dos genes GSTT1 e GSTM1 e investigamos a presença de DNA do EBV e H. pylori. Utilizamos o exon 5 do gene p53 como controle interno da reação de PCR multiplex. Resultados: em um paciente, detectamos genótipos GSTT1 e GSTM1 nulos na área do tumor, em contraste com a presença de ambos os genes nas margens proximal e distal. Encontramos DNA do EBV e H. pylori na área do tumor e também nas margens proximal e distal. Em outro paciente, a margem proximal foi negativa para GSTT1 e o DNA do EBV foi negativo na margem distal. Em três pacientes, o EBV-DNA foi negativo apenas na margem distal. Conclusão: este é o primeiro relato em que diferentes genótipos, infecção por EBV-DNA e H. pylori foram observados no mesmo paciente, indicando provável deleção desses genes em resposta à progressão tumoral e heterogeneidade intratumoral.

ABSTRACT 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.

A study of the association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo in Egyptian patients

Abstract: Background: The association of glutathione S-transferases M1/T1 (GSTM1/T1) null polymorphisms with vitiligo was proposed in several studies including two Egyptian studies with contradictory results. Objective: The aim here was to assess the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo in a larger sample of Egyptian patients with generalized vitiligo. Methods: This study included 122 vitiligo patients and 200 healthy controls that were age, and gender matched. Assessment of GSTM1/T1 gene polymorphisms was done using a multiplex polymerase chain reaction (PCR). Results: Increased odds of generalized vitiligo was observed with the null genotypes of GSTM1 and GSTT1 polymorphisms (P<0.05). Controls with GSTM1 null/GSTT1+ heterozygosis presented with a 2.97 odds protection from having generalized vitiligo (OR=2.97, 95%CI=1.1-7.7) (P=0.02) compared with patients. Study Limitations: Small sample size of patients. Conclusions: This study showed a significant trend towards an association with the combination of the GSTM1/GSTT1 double null polymorphism and generalized vitiligo. Individuals with GSTM1 null/GSTT1+ heterozygosis have a 2.97 odds protection from having generalized vitiligo compared with patients. It was is the first time, to our knowledge, that such an association has been reported.

CYP1A1, CYP1B1, GSTM1 and GSTT1 genetic variants and breast cancer risk in Mexican women / Variantes genéticas de CYP1A1, CYP1B1, GSTM1 y GSTT1, y riesgo de cáncer mamario en mujeres mexicanas

Abstract: 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.

Resumen: Objetivo: Evaluar si las variantes en los genes CYP1A1 (T3801C y A4889G), CYP1B1 (G119T), GSTM1 (indel) yGSTT1 (indel), se asocian con el cáncer de mama (CM) en mujeres mexicanas. Material y métodos: Se parearon por edad (± 5 años) y zona de residencia 952 casos incidentes de CM histológicamente confirmado con 998 controles sanos poblacionales. Se genotipificaron variantes en los genes CYP1A1, CYP1B1, GSTM1 y GSTT1 por discriminación alélica y PCR multiplex. En una submuestra de mujeres, se determinaron 105 marcadores de ancestría. Resultados: Se observó un aumento del riesgo de CM, independiente de otros factores de riesgo, entre las portadoras del genotipo CYP1B1 G119T (T/T vs. G/G: RM=1.9; 95%CI 1.4-2.5). Conclusiones: Nuestros resultados soportan la existencia de susceptibilidad genética para CM conferida por la variante CYP1B1 G119T en mujeres mexicanas.

Genotype association gstm1 null and gastric cancer: evidence-based meta-analysis / Associação do genótipo nulo GSTM1 e o câncer gástrico: evidências baseadas em meta-análise

ABSTRACT BACKGROUND Gastric cancer is the fourth most common cancer in men and the sixth among women, except for non-melanoma skin tumors, in Brazil. Epidemiological evidences reveal the multifactorial etiology of this cancer, highlighting risk factors such as: infection by the bacterium Helicobacter pylori, advanced age, smoking, chronic alcohol abuse, eating habits and genetic polymorphisms. Considering the context of genetic polymorphisms, there is the absence of the GSTM1 gene. The lack of GSTM1 function to detoxify xenobiotics and promote defense against oxidative stress leads to increased DNA damage, promoting gastric carcinogenesis. This process is multifactorial and the development of gastric cancer results from a complex interaction of these variables. OBJECTIVE The aim of this study was to investigate the association of GSTM1 null polymorphism in the pathogenesis of gastric cancer. METHODS A meta-analysis was conducted from 70 articles collected in SciELO and PubMed databases, between September 2015 and July 2016. In order to evaluate a possible association, we used the odds ratio (OR) and confidence interval of 95% (CI 95%). To assess the heterogeneity of the studies was used the chi-square test. Statistical analysis was performed using the BioEstat® 5.3. RESULTS This study included 70 studies of case-control, including 28,549 individuals, which were assessed for the null polymorphism of the GSTM1 gene, and of which 11,208 (39.26%) were cases and 17,341 (60.74%) were controls. The final analysis showed that the presence of the GSTM1 gene acts as a protective factor against the development of gastric cancer (OR=0.788; 95%CI 0.725-0.857; P<0.0001). Positive statistical association was found in Asia (OR=0.736; 95%CI 0.670-0.809; P<0.0001) and Eurasia (OR=0.671; 95%CI 0.456-0.988; P=0.05). However, statistically significant data was not obtained in Europe (OR=1.033; 95%CI 0.873-1.222; P=0.705) and America (OR=0.866; 95%CI 0.549-1.364; P=0.534). Therefore, the results can not be deduced around the world. CONCLUSION This meta-analysis concluded that the presence of the GSTM1 gene is a protector for the emergence of gastric cancer, especially in Asian countries, but this result was not found in Europe and America.

RESUMO CONTEXTO No Brasil, o câncer gástrico é o quarto mais comum em homens e o sexto entre as mulheres, excetuando-se os tumores de pele não melanoma. Aspectos epidemiológicos evidenciam a etiologia multifatorial desta neoplasia, destacando como fatores de risco: a infecção pela bactéria Helicobacter pylori, idade avançada, tabagismo, etilismo crônico, hábitos alimentares e polimorfismos genéticos. No contexto dos polimorfismos genéticos, tem-se a ausência do gene GSTM1. A falta da função de GSTM1 em detoxificar xenobióticos e promover defesa contra o estresse oxidativo, leva ao maior dano do DNA, favorecendo a carcinogênese gástrica. Este processo é multifatorial e o desenvolvimento do câncer gástrico resulta de uma interação complexa dessas variáveis. ObJETIVO O objetivo do presente estudo foi investigar a associação do polimorfismo nulo de GSTM1 na gênese do câncer gástrico. MÉTODOS Foi conduzida uma meta-análise a partir de 70 artigos colhidos dos bancos de dados: SciELO e PubMed, entre setembro de 2015 e julho de 2016. Para avaliar uma possível associação, utilizou-se o odds ratio (OR) e intervalo de confiança de 95% (IC 95%). Para avaliar a heterogeneidade dos estudos, utilizou-se o teste do qui-quadrado. A análise estatística foi realizada utilizando-se o BioEstat® 5.3. RESULTADOS A presente pesquisa contou com 70 estudos do tipo caso-controle que incluíram 28.549 indivíduos avaliados para o polimorfismo nulo do gene GSTM1, dos quais 11.208 (39,26%) eram casos e 17.341 (60,74%) eram controles. A análise final mostra que a presença do gene GSTM1 funciona como um fator de proteção contra o desenvolvimento de câncer gástrico (OR=0,788; IC95% 0,725-0,857; P<0,0001). Associação estatística positiva foi encontrada na Ásia (OR=0,736; IC95% 0,670-0,809; P<0,0001) e Eurásia (OR=0,671; IC95% 0,456-0,988; P=0,05). No entanto, não temos dados com significância estatística da Europa (OR=1,033; IC95% 0,873-1,222; P=0,705) e América (OR=0,866; IC95% 0,549-1,364; P=0,534) para inferir proteção ao câncer gástrico no mundo. CONCLUSÃO Esta meta-análise, conclui que a presença do gene GSTM1 é protetora para o surgimento do câncer gástrico, principalmente nos países asiáticos, porém tal resultado não foi encontrado se comparado isoladamente os estudos realizados na Europa e na América.

Genotypes of GSTM1 and GSTT1: useful determinants for clinical outcome of bladder cancer in Pakistani population

Background: Incidence of bladder cancer has increased rapidly worldwide in the past few years. Environmental as well as genetic factors are involved in the etiology of bladder cancer. Glutathione S transferase mu 1 [GSTM1] and glutathione S transferase theta 1 [GSTT1] genes are two xenobiotic metabolizing genes in phase II of detoxification process

Aim: The current study was aimed to find out the association of different environmental factors and GSTM1 and GSTT1 gene polymorphisms with susceptibility to bladder cancer in Pakistani population

Method: Bladder cancer cases [236] and control blood samples [270] were screened using phenol chloroform method of DNA extraction followed by multiplex PCR

Results: With respect to age; bladder cancer was more prevalent in age >60 years and low grade tumors were more frequent than high grade tumors. Smokers had a significantly higher incidence rate of cancer; also family history of cancer was found to be strongly associated [P < 0.05] with bladder cancer. Commonly reported symptoms by the patients of bladder cancer were hematuria, lower urinary tract symptoms [LUTS] and flank pain. A larger number of patients had undergone surgery, chemotherapy and radiotherapy. Similarly GSTM1 [OR 2.24; CI 1.5-3.2; P = 0.0001] and GSTT1 [OR 2.9; CI 1.4-6.1; P = 0.002] gene deletion showed a highly significant association with bladder cancer. Simultaneous deletions of both GSTM1 and GSTT1 genes also showed highly significant association [OR 5.3; CI 2.1-13.1; P =0.0001] with cancer risk. No association was found when both of the two genes deletion was compared with bladder cancer among smokers

Conclusion: This study suggests that GSTM1 and GSTT1 gene polymorphisms may be associated with increased susceptibility toward bladder cancer in Pakistani population

Polimorfismo nulo dos genes GSTM1 e GSTT1 na suscetibilidade do câncer renal: evidências baseadas em meta-análise / GSTM1 and GSTT1 genes null polymorphisms in kidney cancer susceptibility: evidence based on a meta-analysis

Resumo Introdução O câncer renal é uma doença oncourológica complexa e multifatorial. Objetivo: Realizar uma meta-análise para investigar a associação do polimorfismo nulo dos genes GSTM1 e GSTT1 no contexto do câncer renal. Método: Estudos em seres humanos, do tipo caso-controle, publicados no período de 1999 a 2013, que investigavam a associação do polimorfismo nulo dos genes GSTM1 e GSTT1 no câncer renal, foram agrupados para a confecção da presente meta-análise. Resultados: Foram selecionados 10 artigos sobre o tema proposto. Não foram encontradas associações entre o polimorfismo nulo dos genes GSTM1 (OR = 1,015; IC95% = 0,897-1,147) e GSTT1 (OR = 1,081; IC95% = 0,791- 1,479) e o câncer renal. Conclusões: Conclui-se que os polimorfismos nulos de GSTM1 e GSTT1 não estão associados ao risco do desenvolvimento de câncer renal, pois apresentam papel limitado, se é que existe alguma contribuição efetiva, no desenvolvimento dos tumores renais. .

Abstract Introduction: Renal cancer is a complex and multifactorial oncourologic disease. Objective: To conduct a meta-analysis in order to investigate the association of GSTM1 and GSTT1 genes null polymorphisms in renal cancer. Method: Case-control studies in humans, published from 1999 to 2013, that investigated the association of GSTM1 and GSTT1 genes null polymorphisms in renal cancer were grouped in order to make of this meta-analysis. Results: Ten articles were selected on the subject proposed. No associations were found between polymorphisms of GSTM1-null (OR = 1.015, 95% CI = 0.897 to 1.147) and GSTT1-null (OR = 1.081, 95% CI = 0.791 to 1.479) and renal cancer. Conclusions: Based on the results obtained, we conclude that the GSTM1 and GSTT1 null polymorphisms are not associated with the risk of developing renal cancer, since they have limited role, if there is any on effective contribution in the development of renal tumors. .

Cobertura de la estrategia preventiva de cáncer de vesícula biliar en Chile: Resultados de la Encuesta Nacional de Salud 2009-2010 / Coverage of the gallbladder cancer prevention strategy in Chile: results from the 2009-2010 National Health Survey

Background: In Chile, gallbladder cancer (GBC) is one of the most important causes of death and gallstone disease (GSD) is its main risk factor. Abdominal ultrasonography (AU) is used for the diagnosis of GSD and cholecystectomy is used to prevent it. Aim: To estimate GSD prevalence in the general population and to assess the diagnostic and therapeutic coverage of GSD as a preventive strategy for GBC in Chile. Material and Methods: A standardized digestive symptoms questionnaire of the 2009-2010 Chilean National Health Survey was answered by 5412 adults over 15 years old. Self-reports of AU, GBD and cholecystectomies were recorded. Results: The prevalence of biliary-type pain was 7.1%. During the last five years, the prevalence of AU was 16%. GSD was reported in 20% of these tests and 84% of them were asymptomatic. The prevalence of AU was significantly lower in Araucanía region and among people with less than 12 years of education. Life cholecystectomy prevalence was 11% and reached 40% in people aged over 60 years. Women accounted for 75% of total cholecystectomies. Twenty-one percent of individuals who referred biliary-type pain, were studied with an AU. Only 60% of people with GSD confirmed by AU underwent a cholecystectomy. Conclusions: GSD affects at least 27% of the Chilean adult population. Important deficits and inequities in GSD diagnostic and therapeutic coverage were identified.

[Association of Angiotensin-Converting Enzyme and Glutathione S-Transferase Gene Polymorphisms with body mass index among Hypertensive North Indians]

Objectives: This study aimed to examine the association of angiotensin-converting enzyme [ACE] and glutathione S-transferase [GST] gene polymorphisms with body mass index [BMI] in hypertensive North Indians

Methods: This case-control study was carried out between May 2013 and November 2014 at the Era's Lucknow Medical College and Hospital, Lucknow, India, and included 378 subjects divided into three groups. One group constituted 253 hypertensive individuals [sustained diastolic blood pressure of >90 mmHg and systolic blood pressure of >140 mmHg] who were subcategorised according to normal [<25 kg/m[2]] or high [>/-25 kg/m[2]] BMI. The third group consisted of 125 age-, gender- and ethnically-matched normotensive controls with a normal BMI. Gene polymorphisms were evaluated by polymerase chain reaction. The genotypic and allelic frequency distribution among both groups were analysed

Results: A significant difference was found between GST theta 1-null and GST mu 1-positive genotype frequencies among the hypertensive overweight/obese individuals and controls [P = 0.014 and 0.033, respectively]. However, no difference was observed in the frequency of ACE polymorphisms. ACE insertion/insertion genotype [P = 0.006], insertion and deletion alleles [P = 0.007 each] and GST theta 1-null and GST theta 1-positive genotypes [P = 0.006 each] were found to differ significantly between hypertensive cases and controls, regardless of BMI

Conclusion: ACE and GST gene polymorphisms were not associated with BMI but were significantly associated with hypertension among the studied group of North Indians

Human glutathione S-transferase polymorphisms associated with prostate cancer in the Brazilian population

Objective To evaluate the influence of polymorphisms in GSTA1, GSTM1, GSTT1, and GSTP1 in the risk of developing Prostate Cancer (PCa) in a population of Rio de Janeiro and compare the distribution of allele and genotype frequencies of the polymorphisms analyzed in the present study population with other regions in the country and different ethnic groups. Materials and Methods We analyzed a sample of the Brazilian population, comprising 196 patients with PCa treated by the urology services of the Brazilian National Cancer Institute (INCA) and Mario Kroeff Hospital (HMK), and 208 male blood donors from the Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro (UFRJ). The polymorphisms were determined in DNA, extracted from peripheral blood leucocytes using the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP). Results Our results showed that the distribution of polymorphisms can vary significantly according to the Brazilian region and ethnic groups. The distribution of allele and genotype frequencies of the polymorphism GSTA1 was statistically different between cases and controls. Genotypes (A / B + B / B) were associated with protection (OR = 0.61, 95 % CI = 0.40-0.92) for PCa in comparison to genotype A / A. Conclusion The distribution of genotype frequencies of the polymorphism GSTA1 was statistically different between the case and control groups (p = 0.023), and the presence of genotypes A / B and B / B suggests a protective role against the risk of PCa compared to genotype A / A. This is the first study that reports the genotypic frequency of this polymorphism and its association with PCa in a Brazilian population sample. .

Frequencies of interleukin-6, GST and progesterone receptor gene polymorphisms in postmenopausal women with low bone mineral density / Frequência do polimorfismo da interleucina-6, GST, e dos receptores de progesterona em mulheres na pós-menopausa com baixa densidade mineral óssea

CONTEXT AND OBJECTIVE: Osteoporosis is a skeletal disorder characterized by low bone mineral density (BMD). Studies have shown that some of the genetic components relating to lower BMD may be detected by polymorphisms. Our aim was to evaluate the frequencies of interleukin-6, GST and progesterone receptor gene polymorphisms in postmenopausal women with low BMD. DESIGN AND SETTING: Cross-sectional study, conducted in a public university in São Paulo, Brazil. METHODS : We evaluated interleukin-6 (IL-6), progesterone receptor gene (PROGINS) and glutathione S-transferase (GST) polymorphisms in 110 postmenopausal women with no previous use of hormone therapy. Tests were performed using DNA-PCR, from oral scrapings. We used Student's t-test and a logistic regression model for statistical analysis. RESULTS : Regarding IL-6 polymorphism, 58.2% of the patients were homozygotes (GG) and 41.8% had allele C (heterozygote or mutant homozygote + GC or CC). PROGINS genotype polymorphism was absent in 79% (wild homozygote or P1/P1) and present in 20.9% (heterozygote or P1/P2). Regarding GSTM1 polymorphism, the allele (1/1) was present in 72.7% of the patients and was absent in 27.3%. We found that IL-6 polymorphism had statistically significant correlations with the L2-L4 T-score (P = 0.032) and with BMD (P = 0.005). Women with IL-6 polymorphism were 2.3 times more likely to have a L2-L4 T-score of less than -1, compared with those not presenting this polymorphism. CONCLUSION: IL-6 gene polymorphism was correlated with low BMD, whereas the PROGINS and GSTM1 polymorphisms did not show any correlation. .

CONTEXTO E OBJETIVO: A osteoporose é uma desordem esquelética caracterizada por baixa densidade mineral óssea. Estudos têm demonstrado que alguns componentes genéticos relacionados com a menor densidade mineral óssea podem ser detectados por polimorfismos. Nosso objetivo foi avaliar a presença do polimorfismo de genes em mulheres pós-menopáusicas com baixa densidade mineral óssea. TIPO DE ESTUDO E LOCAL: Estudo transversal, conduzido em universidade pública em São Paulo, Brasil. MÉTODOS: Avaliamos os polimorfismos relacionados à interleucina-6 (IL-6), o gene receptor de progesterona (PROGINS) e glutationa S-transferase (GST) em 110 mulheres na pós-menopausa sem terapia hormonal prévia. Os testes foram realizados com DNA-PCR a partir de raspados orais. Foram utilizados teste t de Student e modelo de regressão logística para análise estatística. RESULTADOS: Em relação ao polimorfismo IL-6, 58,2% dos pacientes eram homozigotos (GG) e 41,8% tinham o alelo C (heterozigoto ou homozigoto mutante + GC ou CC). Nos genótipos do polimorfismo PROGINS, 79% estavam ausentes (homozigoto selvagem ou P1/P1) e 20,9% presentes (heterozigoto ou P1/P2). No polimorfismo do GSTM1, o alelo (1/1) estava presente em 72,7% dos pacientes e ausente em 27,3%. Encontramos significância estatística entre o polimorfismo genético da IL-6 com o T-score de L2-L4 (P = 0,032) e a densidade mineral óssea (P = 0,005). As mulheres com polimorfismo da IL-6 tiveram 2,3 vezes mais chance de ter menos de -1 na L2-L4 T-score, quando comparadas às não portadoras. CONCLUSÃO: O polimorfismo do gene da IL-6 está correlacionado com baixa densidade mineral óssea, enquanto os polimorfismos GSTM1 e PROGINS não mostraram correlação. .

Association between Glutathione S-Transferase T1, M1, and P1 Genotypes and the Risk of Colorectal Cancer

Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens. Genetic polymorphisms within the genes encoding for GSTs may therefore cause variations in their enzyme activity, which may in turn influence the interindividual susceptibility to cancers. In this study, we aimed to investigate the association between genetic polymorphisms of GSTT1, GSTM1, and GSTP1 and the risk of colorectal cancer (CRC) in 264 cases and 317 controls in a Chinese population. Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Our results showed that individuals with GSTT1 and GSTM1 null genotypes exhibited a higher risk of CRC (GSTT1, OR,1.66; 95% CI, 1.20-2.31, P=0.003; GSTM1, OR,1.57; 95% CI,1.13-2.18, P=0.007), while no association was observed for GSTP1 (P(heterozygous)=0.790 or P(variant)=0.261). Furthermore, individuals who simultaneously carried the null genotypes for both GSTT1 and GSTM1 showed a stronger risk association (OR, 1.95; 95% CI, 1.33-2.85; P<0.001). In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.

Polymorphisms of GSTM1 and GSTT1 genes in breast cancer susceptibility: a case-control study / Polimorfismo dos genes GSTM1 e GSTT1 na suscetibilidade do câncer de mama: estudo caso-controle

PURPOSE: This study aimed to evaluate the frequency of homozygous deletion of GSTM1 and GSTT1 genes and their combinations between patients with breast cancer and healthy individuals, associating them with disease susceptibility. METHODS: This is a case-control study in which 49 women diagnosed with breast cancer confirmed by pathological examination and 49 healthy women with no evidence of cancer and no prior family history of breast cancer were invited to participate. All of them answered a questionnaire with epidemiological data and were submitted to blood sample collection. Genomic DNA was extracted from blood, and genotyping was performed by polymerase chain reaction. Data were analyzed with SPSS 20.0. RESULTS: The frequency of null alleles for GSTM1 and GSTT1 was 58.8 and 61.7%, respectively, for patients with breast cancer, and 41.2 and 38.3%, respectively, in control patients. In homozygous deletion of the GSTM1 gene, a significantly higher frequency was found in the breast cancer cases. CONCLUSION: Breast cancer patients presented higher frequency of homozygous deletion of the GSTM1 gene compared with the control group.

OBJETIVO: Este estudo teve como objetivo avaliar a frequência de deleção homozigótica dos genes GSTM1 e GSTT1 e suas combinações entre os pacientes com câncer de mama e indivíduos saudáveis, associando-se a suscetibilidade à doença. MÉTODOS: Este é um estudo de caso-controle, no qual 49 mulheres diagnosticadas com câncer de mama confirmado por exame anatomopatológico e 49 mulheres saudáveis, sem evidência de câncer e sem história familiar prévia de câncer de mama, foram convidadas a participar. Todas responderam a um questionário com dados epidemiológicos e foram submetidas à coleta de sangue. O DNA foi extraído a partir de sangue, e genotipagem foi realizada por reação em cadeia da polimerase. Os dados foram analisados com o SPSS 20.0. RESULTADOS: A frequência de alelos nulos para GSTM1 e GSTT1 foi de 58,8 e 61,7%, respectivamente, para as pacientes com câncer de mama, e 41,2 e 38,3%, respectivamente, em pacientes do grupo controle. Em deleção homozigótica do gene GSTM1, uma frequência significativamente maior foi encontrada nos casos. CONCLUSÃO: Pacientes com câncer de mama apresentam uma maior frequência de deleção homozigótica do gene GSTM1 quando comparadas com o grupo controle.

Nullity of GSTT1/GSTM1 related to pesticides is associated with Parkinson's disease / Nulidade de GSTT1/GSTM1 relacionada a pesticidas associa-se com doenca de Parkinson

Genetic and environmental factors affect the pathogenesis of Parkinson's disease (PD). Genetic variants of the enzyme glutathione S-transferases (GST) may be related to the disease. This study aimed to evaluate the influence of genetic variants of GST (GSTT1/GSTM1) and their association with the exposure to environmental toxins in PD patients. We studied 254 patients with PD and 169 controls. The GSTM1/GSTT1 variants were analyzed by polymerase chain reaction. We applied the Fisher's exact test and the χ2 test for statistical analysis (p<0.05). The present and absence for GSTT1 and GSTM1 were similar in patients and controls. The null for GSTT1 and GSTM1 (0/0) and exposure to pesticides prevailed in patients (18%) compared to controls (13%, p=0.014). This study suggests the association between PD and previous exposure to pesticides, whose effect may be enhanced in combination with null for GSTT1/GSTM1.

Fatores genéticos e ambientais influenciam a patogênese da doença de Parkinson (DP). Variantes genéticas das enzimas glutationa S-transferases (GST) parecem estar envolvidas com a doença. Os objetivos deste estudo foram avaliar a influência de variantes genéticas de GST (GSTT1/GSTM1) e sua associação com exposição a toxinas ambientais em pacientes com DP. Foram estudados 254 pacientes com DP e 169 controles. As variantes para GSTM1/GSTT1 foram analisadas por reação em cadeia da polimerase. Para análise estatística foram aplicados os testes de Fisher e do χ2 (p<0,05). Tanto a presença quanto a nulidade para GSTT1 e GSTM1 foram semelhantes em pacientes e controles. A nulidade para GSTT1 e GSTM1 (0/0) e contato com agrotóxicos prevaleceu nos pacientes (18%) em relação aos controles (13%, p=0,014). Este estudo sugere associação entre DP e contato prévio com agrotóxicos, cujo efeito parece potencializado em combinação com nulidade para GSTT1/GSTM1.

Frecuencia de los polimorfismos CYP1A1*2A y deleción del gen GSTM1 en pacientes con carcinoma de células escamosas de laringe en relación al hábito tabáquico: estudio piloto en Chile / Frequency of CYP1A1*2A and GSTM1 gene polymorphisms in Chilean patients with squamous cell carcinoma of the larynx in relation to smoking habit: a pilot study

Introducción: Entre los factores de riesgo para cáncer laríngeo (CL) son relevantes el consumo de tabaco y alcohol. Estos xenobióticos son metabolizados por un grupo de enzimas, entre las cuales están CYP1A1 y GSTM1, cuyas variantes polimórficas se postulan como factores de riesgo para esta enfermedad. Objetivos: Describir la frecuencia de las variantes de los polimorfismos de CYP1A1 y GSTM1 en un grupo de pacientes diagnosticados con CL. Analizar la posible correlación entre las variantes genéticas de ambas enzimas y la presencia de CL. Evaluar la influencia del hábito tabáquico en el riesgo de aparición de cáncer escamoso de laringe en pacientes con genotipos de riesgo. Material y método: Se seleccionaron 35 pacientes con CL entre los años 2000 y 2010 en Servicio de Otorrinolaringología del HBLT y 124 controles reclutados en el Centro de Investigaciones Farmacológicas y Toxicológicas (IFT). A todos los individuos se les registraron datos demográficos y extrajo una muestra de sangre para analizar las variantes polimórficas de CYP1A1 y GSTM1, mediante PCR-RFLP. Resultados: De un total de 35pacientes 54,3% presentan el genotipo GSTM1 (-/-) y 17,1% el genotipo CYP1A1*2A C/C. En el grupo control (n =140) estas frecuencias fueron de 19,35°% y 10,48%o, respectivamente. Se observó una correlación entre GSTM1 y el CL, estratificado por el hábito tabáquico y alcohólico. No se encontraron relaciones estadísticamente significativas con el hábito alcohólico y/o tabáquico. No se observaron asociaciones entre la patología y la combinación de genotipos o entre genotipos y el hábito tabáquico o alcohólico. Conclusiones: Los resultados muestran una asociación estadísticamente significativa entre la deleción de GSTM1 (-/-) y el riesgo de presentar CL, lo que refleja el importante papel que juega esta enzima en la desintoxicación de compuestos cancerígenos. Sin embargo, se requiere incrementar el número de pacientes para establecer apropiadamente la relación genético-ambiental que permite adjudicar un papel relevante a estos biomarcadores.

Introduction: Tobacco and alcohol consumption are recognized risk factors for squamous cell carcinoma of the larynx. These xenobiotics are metabolized by numerous enzymes, among which, CYP1A1 and GSTM1 gene polymorphisms have been identified as risk factors for developing tobacco related cancers as lung and laryngeal carcinomas. Nevertheless, these polymorphisms have not been studied in Chilean patients with squamous cell carcinoma of the larynx. Aim: To describe, for the first time, the frequency of CYP1A1 and GSTM1 gene polymorphisms in Chilean patients with squamous cell carcinoma of the larynx. Material and method: We conducted a case-control study. The case group consisted of 35 Chilean patients with squamous cell carcinoma of the larynx; the control group was formed by 124 Chilean subjects without cancer diagnosis. Demographic data as age, sex and quantification of tobacco smoking and alcohol consumption were recorded in all individuals. CYP1A1 and GSTM1 gene polymorphisms were evaluated by polymerase chain reaction and restriction enzymes (PCR-RFLP). Results: The frequency of CYP1A1*2A C/C genotype was 54, 3°% among laryngeal cancerpatients and 17,1%% among control subjects. The frequency ofGSTM1 (-/-) genotype was 19,35 %% among laryngeal cancer patients and 10,48%% among control subjects. There were no statistically significant relationships between this gene polymorphisms and tobacco smoking or alcohol consumption. There were no associations between the presence of both gene polymorphisms in the same individual and the presence of laryngeal cancer. Interestingly we found an OR of 8.69 (CI 2.90 to 26.01) for GSTM1 (-/-) polymorphism and laryngeal cancer, stratified by tobacco smoking and alcohol consumption. Conclusions: Our work shows that the deletion of GSTM1 could be an important risk factor for squamous cell carcinoma of the larynx in Chilean patients. This finding reflects the important role that detoxification of carcinogenic compounds plays in Chilean population. However, it is necessary to increase the number of studied patients to properly establish the genetic-environmental relationship ascribed to these biomarkers.

GSTM1, GSTT1, and GSTP1 polymorphisms, breast cancer risk factors and mammographic density in women submitted to breast cancer screening / Polimorfismos GSTM1, GSTT1 e GSTP1, fatores de risco para câncer de mama e densidade mamográfica em mulheres submetidas a rastreamento mamográfico

Genetic polymorphisms in genes related to the metabolism of xenobiotics, such as genes of the glutathione S-transferases (GSTM1, GSTT1, and GSTP1) superfamily have been associated with an increased risk for breast cancer (BC). Considering the high incidence of BC in the city of Porto Alegre in southern Brazil, the purpose of this study was to characterize genotypic and allelic frequencies of polymorphisms in GSTM1, GSTT1, and GSTP1, and correlate these molecular findings with established risk factors for breast cancer including mammographic density, in a sample of 750 asymptomatic women undergoing mammographic screening. Molecular tests were performed using the multiplex polymerase chain reaction (PCR) for GSTM1 and GSTT1, and quantitative PCR for GSTP1 polymorphisms. Overall, the frequencies of GSTM1 and GSTT1 null genotypes were 45% and 21%, respectively. For GSTP1 polymorphism, genotypic frequencies were 44% for the Ile/Ile genotype, 44% for the Ile/Val genotype, and 12% for Val/Val genotype, with an allelic frequency of 66% for the wild type allele in this population, similar to results of previous international publications. There was a statistically significant association between the combined GSTM1 and GSTT1 null genotypes (M-/T-) and mammographic density in post menopausal women (p = 0.031). When the GSTT1 null (T-) genotype was analyzed isolated, the association with mammographic density in post menopausal women and in the overall sample was also statistically significant (p = 0.023 and p = 0.027, respectively). These findings suggest an association of GSTM1 and GSTT1 null genotypes with mammographic density.

Polimorfismos genéticos em genes relacionados com o metabolismo de xenobióticos, como os genes da superfamília das glutationa S-transferases (GSTM1, GSTT1 e GSTP1) têm sido associados com o aumento do risco para câncer de mama (CM). Considerando a alta incidência de CM na cidade de Porto Alegre, região Sul do Brasil, a proposta deste estudo foi caracterizar genótipos e frequências alélicas dos polimorfismos GSTM1, GSTT1 e GSTP1, e correlacionar esses achados moleculares com fatores de risco já estabelecidos para câncer de mama, incluindo densidade mamográfica, em uma amostra de 750 mulheres assintomáticas durante o rastreamento mamográfico. Para os testes moleculares foi utilizado multiplex da reação em cadeia de polimerase (PCR) para GSTM1 e GSTT1, e PCR quantitativo para o polimorfismo GSTP1. As frequências dos genótipos GSTM1 e GSTT1 nulos foram 45% e 21%, respectivamente. Para o polimorfismo GSTP1, as frequências genotipicas foram: 44% para o genótipo Ile/Ile, 44% para o genótipo Ile/Val e 12% para o genótipo Val/Val. A frequência do alelo lle nesta população foi 66%, semelhante a outros estudos. Houve uma associação significativa entre a combinação dos genótipos (T-/M-) nulos e densidade mamográfica nas mulheres pós-menopáusicas (p = 0,031). Quando analisamos isoladamente o genótipo GSTT1 nulo (T-) também encontramos uma associação significativa com a densidade mamográfica nas mulheres pós-menopáusicas (p = 0,027) e na amostra total. Estes achados sugerem uma associação dos genótipos (T-/M-) nulos com densidade mamográfica.

Mutações do gene cystic fibrosis transmembrane conductance regulator e deleções dos genes glutationa S-transferase em pacientes com fibrose cística no Brasil / Cystic fibrosis transmembrane conductance regulator gene mutations and glutathione S-transferase null genotypes in cystic fibrosis patients in Brazil

OBJETIVO: Determinar os efeitos que a mutação do gene cystic fibrosis transmembrane conductance regulator (CFTR) e da deleção dos genes glutationa S-transferase (GST) mu-1 (GSTM1) e teta-1 (GSTT1) têm na evolução clínica da fibrose cística (FC) em pacientes da região sudeste do Brasil. MÉTODOS: Entre março de 2002 e março de 2005, incluímos no estudo todos os pacientes com FC atendidos consecutivamente no Departamento de Pediatria do Hospital de Clínicas da Faculdade de Ciências Médicas da Universidade Estadual de Campinas. O DNA genômico de 66 pacientes com FC foi analisado por PCR e digestão com endonuclease de restrição para a identificação dos genótipos. RESULTADOS: A mutação ΔF508 do gene CFTR foi identificada em 44 (66,7 por cento) pacientes. As deleções dos genes GSTM1, GSTT1 e da combinação nula GSTM1/GSTT1 foram identificadas em 40,9 por cento, 15,2 por cento e 3,0 por cento dos pacientes, respectivamente. A mutação ΔF508 do gene CFTR foi mais comum em pacientes diagnosticados com FC antes dos 2,5 anos de idade que naqueles diagnosticados mais tarde (75,5 por cento vs. 41,2 por cento; p = 0,008). CONCLUSÕES: Foram observadas frequências similares da mutação ΔF508 do gene CFTR e dos genótipos GSTM1 e GSTT1 nos pacientes, independentemente do sexo, etnia ou status da doença pulmonar ou pancreática. Quando os pacientes foram estratificados por aspectos clínicos e epidemiológicos, as frequências dos genótipos GSTM1 e GSTT1 nulos foram semelhantes, sugerindo que a ausência herdada dessas vias enzimáticas não altera o curso da FC. Em contraste, a alta frequência da mutação ΔF508 no gene CFTR encontrada em pacientes mais jovens sugere que essa mutação influencia a idade no momento do diagnóstico de FC nessa região do país.

OBJECTIVE: To determine the effects that mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and deletion of the glutathione S-transferase (GST) genes mu-1 (GSTM1) and theta-1 (GSTT1) have on the clinical course of cystic fibrosis (CF) in patients residing in the southeastern region of Brazil. METHODS: The study sample consisted of all consecutive CF patients treated at the Hospital de Clínicas School of Medical Sciences of the State University at Campinas between March of 2002 and March of 2005. We included 66 CF patients. Genomic DNA was analyzed by polymerase chain reaction and restriction endonuclease digestion for the identification of the genotypes. RESULTS: The DF508 mutation of the CFTR gene was found in 44 patients (66.7 percent). The null genotypes GSTM1, GSTT1 and GSTM1/GSTT1 were found in 40.9 percent, 15.2 percent, and 3.0 percent of the patients, respectively. The DF508 CFTR mutation was more common in patients diagnosed with CF before 2.5 years of age than in those diagnosed later (75.5 percent vs. 41.2 percent; p = 0.008). The frequency of the DF508 CFTR mutation, as well as of the GSTM1 and GSTT1 genotypes, was not found to be associated with gender, ethnicity, pulmonary disease status, or pancreatic disease status. CONCLUSIONS: When the patients were stratified by clinical and epidemiological features, the frequencies of the GSTM1 and GSTT1 null genotypes were similar, suggesting that the inherited absence of these enzymatic pathways does not alter the course of CF. However, the high frequency of the DF508 CFTR mutation found in younger children suggests that it influences the age at diagnosis of CF in this region of Brazil.

Gene expression of a putative glutathione S-transferase is responsive to abiotic stress in embryogenic cell cultures of Cyclamen persicum

Background: Cyclamen persicum is an economically important ornamental crop that is propagated exclusively through seeds as vegetative propagation using cuttings is not possible. Therefore a micropropagation method through somatic embryogenesis is of high interest; however the method suffers from low reliability concerning quality and quantity of the produced plantlets. A crucial step of the protocol is the removal of plant growth regulators (PGRs) that triggers embryo development. In order to get a better insight in this crucial step of the propagation process, a gene expression analysis has been set up using five different genes of glutathione S-transferases (GST) as these are known to be auxin responsive as well as stress reactive. Results: One out of the five genes of glutathione S-transferases (CpGST1) displayed a clear down-regulation 72 hrs after removal of PGRs compared to 4 hrs after, implying auxin responsiveness. However, a more detailed analysis including the time points 0, 4 and 72 hrs revealed an initial strong up-regulation after 4 hrs before it was down-regulated after 72 hrs. In comparison fold-changes of the additional four GST-genes were marginal. Comparing cultures on semisolid medium to that in suspension, transcript abundances of CpGST1 were clearly decreased in suspension culture. Conclusions: Against the initial hypothesis CpGST was not auxin responsive but stress reactive, probably especially indicating drought stress imposed on the cells upon transfer from submerged suspension culture to semisolid medium. Mechanical stress caused by shaking of suspensions cultures seemed to be less important.

Tabaquismo, Glutation S-Transferasa, N-Acetiltransferasa 2 y riesgo de cáncer de vejiga / Tabaquism, S-Transferase Glutation, N-Acetiltrasferase 2 and bladder cancer risk

El hábito tabáquico es el factor de riesgo más conocido para cáncer de vejiga. Ciertas arilaminas presentes en el cigarrillo han sido identificadas como carcinógenos para la vejiga en humanos. El objetivo de nuestro estudio es establecer el riesgo de padecer de cáncer de vejiga en individuos fumadores, acetiladores lentos para NAT2 y genotipos nulos de GSTM1 y GSTT1. Materiales y métodos: Se reunieron en total 150 pacientes, 75 pertenecientes al grupo de carcinoma urotelial de vejiga y 75 del grupo control, en este último no se incluyeron pacientes con enfermedad neoplásica de ninguna índole. El ADN se aisló de la muestra de sangre a partir de linfocitos utilizando un kit disponible comercialmente (QIAmp DNA Blood Mini and Maxi Kit, QIAGen GMBH). Mediante el uso de técnicas de reacción en cadena de polimerasa y de restricción/ fragmentación se determinaron los polimorfismos de las enzimas: NAT2, GSTT1 y GSTM1.Resultados: Se incluyeron un total de 150 pacientes, de los cuales 75 pertenecían al grupo controly 75 al grupo de cáncer de vejiga, la media de edad del grupo de cáncer de vejiga fue 60,5 +/-11,4 y del grupo control fue 51,3 +/- 11,4. En cuanto al género en grupo de cáncer de vejiga 64 por ciento pertenecían al sexo masculino. En el grupo control 41 por ciento pertenecían al sexo masculino. Al estudiar el hábito tabáquico se halló que 51 por ciento de los pacientes del grupo de cáncer de vejiga continuaban siendo fumadores, mientras que sólo 21 por ciento fumaba en el grupo control. En el análisis de los genotipos de la enzima NAT2 en el grupo de los pacientes con cáncer de vejiga 52 por ciento resultaron acetiladores lentos, y 4 por ciento acetiladores rápidos. En el grupo control 45 por ciento de los pacientes eran acetiladores lentos y 12 por ciento acetiladores rápidos. En cuanto a la determinación de GSTT1 19 por ciento de los pacientes del grupo de cáncer de vejiga y 24 por ciento del grupo control exhibieron el genotipo nulo...

Introduction: Smoking is the most studied risk factor for bladder cancer. Certain arilamines present in cigarettes have been identified as carcinogenic for the bladder in humans. The purpose of this study is to establish the risk of bladder cancer in smokers, slow acetilators for NAT2 and none active genotypes for GSTM1 and GSTT1. Material and methods: 150 patients were studied, 75 in the group of urothelial carcinoma of the bladder and 75 in the control group. The DNA was isolated from lymphocytes of blood samples using commercially available kit (QIAmp DNA Blood Mini and Maxi Kit, QIAG en GMBH). Enzyme polymorphisms of NAT2, GSTT1 and GSTM1 were determined using techniques of polymerase chain reaction and restriction/fragmentation. Results: 150 patients were included, of who 75 belonged to the control group and 75 had bladder cancer, the average of age of the bladder cancer group was 60.5 +/- 11.4 and of the control group 51.3 +/- 11.4. Regarding gender, in the bladder cancer group 64 percent were males. In the control group 41percent were males. 51 percent of the patients in the bladder cancer group continued being smokers, whereas only 21 percent smoked in control group. In NAT2 enzyme genotype analysis the bladder cancer group 52 percent were slow acetilators, and 4 percent fast acetilators. In the control group 45 percent were slow acetilators and 12 percent fast acetilators. Regarding GSTT1 determination, 19 percent of the bladder cancer group and 24 percent of the control group showed the non-active genotype. GSTM1 showed its non-active form in 44 percent of the bladder cancer group and 48 percent of the control group. Discussion: Bladder cancer is clearly related with smoking habit. We observed a very significant relationship when evaluating smoking habit, slow acetilators for NAT2, and none-active genotypes of GSTM1 and bladder cancer...