Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta

Nelson, Heather H.; Wiencke, John K.; Christiani, David C.; Cheng, Tsun‐Jen; Zuo, Zheng Fa; Schwartz, Brian; Lee, Byung Kook; Spitz, Margaret R.; Wang, Min; Xu, Xiping; Kelsey, Karl T.

doi:10.1093/carcin/16.5.1243

Cited by 303 publications

(169 citation statements)

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“…Among the GST enzyme superfamily, disease associations with functional variation of 3 members (GSTM1, GSTT1, and GSTP1) have been studied extensively. The GSTP1*Ile105Val SNP and GSTM1-null and GSTT1-null genes are common, occurring in 20-25% of African Americans (69)(70)(71). GST genes also catalyze metabolic pathways for detoxification of reactive oxygen compounds that may be generated by ultraviolet radiation in sunlight.…”

Section: Discussionmentioning

confidence: 99%

Effect of glutathione S‐TRANSFERASE polymorphisms and proximity to hazardous waste sites on time to systemic lupus erythematosus diagnosis: Results from the roxbury lupus project

Karlson¹,

Watts²,

Signorovitch³

et al. 2007

Arthritis & Rheumatism

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Objective. The high prevalence of systemic lupus erythematosus (SLE) among African American women may be due to environmental exposures, genetic factors, or a combination of factors. Our goal was to assess association of residential proximity to hazardous waste sites and genetic variation in 3 glutathione Stransferase (GST) genes (GSTM1, GSTT1, and GSTP1) with age at diagnosis of SLE.Methods. Residential histories were obtained by interviewing 93 SLE patients from 3 predominantly African American neighborhoods in Boston. Residential addresses and locations of 416 hazardous waste sites in the study area were geocoded using ArcView software. Time-varying Cox models were used to study the effect of residential proximity to hazardous sites, GST genotype, and interaction between genotype and exposure in determining age at diagnosis.Results. The prevalence of SLE among African American women in these neighborhoods was 3.56 SLE cases per 1,000. Homozygosity for GSTM1-null and GSTP1 Ile105Val in combination was associated with earlier SLE diagnosis (P ‫؍‬ 0.03), but there was no association with proximity to 416 hazardous sites. Available data on specific site contaminants suggested that, at a subset of 67 sites, there was higher potential risk for exposure to volatile organic compounds (P < 0.05 with Bonferroni correction). GST genotypes had a significant interaction with proximity (P ‫؍‬ 0.03) in analyses limited to these sites.Conclusion. There was no independent association between residential proximity to hazardous waste sites and the risk of earlier SLE diagnosis in this urban population. However, analysis of a limited number of sites indicated that the risk of earlier SLE associated with proximity to hazardous sites might be modulated by GST polymorphisms.

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Section: Discussionmentioning

confidence: 99%

Effect of glutathione S‐TRANSFERASE polymorphisms and proximity to hazardous waste sites on time to systemic lupus erythematosus diagnosis: Results from the roxbury lupus project

Karlson¹,

Watts²,

Signorovitch³

et al. 2007

Arthritis & Rheumatism

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“…O gene da classe Mu (GSTM1) e o gene da classe Theta (GSTT1) são polimórficos em humanos e estão ausentes ou deletados de forma homozigótica em 40% a 50% e 16% a 24% das diferentes populações étnicas, respectivamente [9][10] . Estudos epidemiológicos sugerem que indivíduos com deleção homozigótica do GSTM1 e do GSTT1 apresentam risco elevado de desenvolver vários tipos de neoplasia, incluindo câncer de bexiga, cólon, pulmão, pele e estômago 9 .…”

Section: Introductionunclassified

Características mamográficas do câncer de mama associadas aos polimorfismos GSTM1 e GSTT1

Morais¹,

Filho²,

Lourenço³

et al. 2008

Rev. Assoc. Med. Bras.

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RESUMO INTRODUÇÃO.As enzimas do sistema da glutationa S-transferase (GST) modulam os efeitos da exposição a vários agentes citotóxicos e genotóxicos. Os genes GSTM1 e GSTT1 são polimórficos em humanos e suas deleções têm sido associadas ao aumento do risco de várias neoplasias, dentre elas o câncer de mama. OBJETIVO. Comparar a freqüência das deleções dos genes GSTM1 e GSTT1 em mulheres sadias e com câncer de mama e comparar as características mamográficas do câncer entre mulheres portadoras e não portadoras das referidas deleções. MÉTODOS. Foram determinadas as freqüências das referidas deleções por PCR em 100 pacientes portadoras de câncer de mama esporádico tratadas de setembro de 2004 a junho de 2005 e em 169 mulheres sadias doadoras de sangue no mesmo período e comparadas através do odds ratio (OR) com seus respectivos IC 95%. Foram revistos os prontuários e as mamografias das pacientes com câncer e avaliadas características mamográficas (padrão de distribuição do parênquima fibroglandular, achados mamográficos ao diagnóstico e classificação BI-RADS), correlacionando-as às deleções gênicas através do cálculo da RP (razão de prevalência) com seus respectivos IC 95%. Resultados. O GSTM1 esteve deletado em 40% dos cânceres e em 44,4% dos controles (OR=1,20; IC 95% 0,70-2,04; p=0,5659) enquanto o GSTT1 em 20% e 19,5%, respectivamente (OR=0,73; IC 0,37-1,44; p=0,4124). O padrão mamográfico denso esteve associado à deleção homozigótica do GSTM1 (RP= 2,43; IC 1,11-4,08). Não se observou associação entre as deleções do sistema GST e achados mamográficos ao diagnóstico e classificação BI-RADS. Conclusão. A deleção homozigótica do gene GSTM1 associou-se ao padrão mamográfico denso.Unitermos: Glutationa S-transferase. GSTM1. GSTT1. Câncer de mama. Mamografia. CARACTERÍSTICAS CARACTERÍSTICAS CARACTERÍSTICAS CARACTERÍSTICAS CARACTERÍSTICAS MAMOGRÁFICAS MAMOGRÁFICAS MAMOGRÁFICAS MAMOGRÁFICAS MAMOGRÁFICAS DO INTRODUÇÃOO câncer de mama (CM) é a segunda neoplasia maligna mais freqüente no mundo e a primeira entre as mulheres 1 . Embora uma fração substancial dos casos possa ser explicada pela associação de fatores de risco bem estabelecidos -idade, menarca precoce, menopausa tardia, nuliparidade ou primiparidade em idade avançada, história de doença mamária benigna e história familiar de câncer mamário em um ou mais parentes de primeiro grau 2 -a razão para o aumento na incidência em todo o mundo ainda é desconhecida 3 .Estudos epidemiológicos sugerem que carcinógenos ambientais devem contribuir para esse aumento 3 e que diferenças genéticas no metabolismo desses carcinógenos podem também estar associadas a variações individuais na susceptibilidade ao CM 4 .A glutationa S-transferase (GST) é uma família de enzimas intracelulares, que impedem a ação de toxinas endógenas e exógenas sobre as células, evitando assim danos ao DNA celular 7 . Como estão envolvidas no metabolismo de muitos carcinógenos, poluentes ambientais e drogas anticancerígenas, é, portanto, razoável supor que a falta de isoenzimas específicas tenha um efeit...

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“…Human GST forms such as GST M1-1 and T1-1 are not expressed in approximately half of the population, and hereditary differences in their expression are due to deletion of the encoding genes [17,18]. Loss of these genes has been suggested as a possible marker for greater susceptibility to development of lung cancer, as well as other cancers [19,20].…”

Section: Introductionmentioning

confidence: 99%

Polymorphism of the glutathione transferase subunit 3 in Sprague–Dawley rats involves a reactive cysteine residue

Kumano

Kimura

Hayakari

et al. 2000

Biochemical Journal

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Comparison of Hirosaki hairless rat (HHR) and SpragueDawley (SD) rat liver glutathione transferase (GST) subunits by HPLC revealed differences in subunit 3 ; a new peak was detected in HHR GSTs and this was tentatively named X. By chromatofocusing, the HHR GST form composed of peak X and SD rat GST 3-3 were eluted at pH 8.8 and 9.1 respectively. The former was more sensitive to the SH reagent N-ethylmaleimide (NEM) than the latter. GSSG treatment of peak X resulted in a shift of retention time (peak Y) by HPLC analysis. However, such conversion was not observed for the SD rat GST 3-3 following GSSG or dithiothreitol (DTT) treatment. Peak Y exhibited m\z values of 26091.9 and 26125.4 by matrix-assisted laser-desorption ionization-time-of-flight MS, higher than those of peak X by 304-307, equivalent to the molecular-mass value of GSH. On treatment with DTT, peak Y was converted into peak X, with release of a substance with HPLC-characteristics of GSH. This substance was confirmed to be GSH by liquid chromatography\ MS. These results thus indicated peak Y to be a glutathionylated form of peak X. Quantification revealed the release of

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Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta

Cited by 303 publications

References 0 publications

Effect of glutathione S‐TRANSFERASE polymorphisms and proximity to hazardous waste sites on time to systemic lupus erythematosus diagnosis: Results from the roxbury lupus project

Effect of glutathione S‐TRANSFERASE polymorphisms and proximity to hazardous waste sites on time to systemic lupus erythematosus diagnosis: Results from the roxbury lupus project

Características mamográficas do câncer de mama associadas aos polimorfismos GSTM1 e GSTT1

Polymorphism of the glutathione transferase subunit 3 in Sprague–Dawley rats involves a reactive cysteine residue

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