Allelotype influence at glutathione S-transferase M1 locus on breast cancer susceptibility

Charrier, J.; Maugard, Christine M.; Mevel, B. Le; Bignon, Yves‐Jean

doi:10.1038/sj.bjc.6690055

Cited by 42 publications

(26 citation statements)

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“…Although previous studies observed a significant interaction between GSTM1-null, GSTT1-null genotypes and alcohol consumption in the risk for breast cancer among premenopausal women (Park et al, 2000) and among both pre-and postmenopausal women (Helzlsouser et al, 1998), the potential association between individual GSTM1 alleles and breast cancer or their interaction with alcohol consumption in modifying the risk of breast cancer was not investigated. Our findings in this study are, however, consistent with those in several reports indicating potential differences in the effects of GSTM1A and GSTM1B in breast and other cancers (Fryer et al, 1993a, b;Duncan et al, 1995;Inskip et al, 1995;Charrier et al, 1999). There is also the possibility that GSTM1 may be linked to another gene involved in the metabolism of putative breast carcinogens.…”

Section: Discussioncontrasting

confidence: 46%

Glutathione S-transferase M1 and T1 genetic polymorphisms, alcohol consumption and breast cancer risk

et al. 2003

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Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and GSTT1 genetic polymorphisms, and to evaluate the effect modification between GST genotypes and alcohol consumption in the risk of breast cancer, we conducted a case -control study in the state of Connecticut in the period 1998 and 2001. Cases were histologically confirmed, incident breast cancer patients in New Haven County, CT. Controls were randomly selected from women histologically confirmed to be without breast cancer. The study results show that, while GSTM1 genotypes were not associated with breast cancer risk, GSTT1-null genotype was associated with a significant 90% increased risk for postmenopausal women (OR ¼ 1.9, 95% CI 1.2 -3.0). Analysis by GST genotypes and alcohol consumption shows that GSTM1A ever-drinking women had a 2.5-fold (OR ¼ 2.5, 95% CI 1.1 -5.5) increased risk of breast cancer compared to the GSTM1A never-drinkers, and the risk increases with duration and daily amount of alcohol consumption. Postmenopausal women with GSTT1-null genotype, who consumed a lifetime of 4250 kg of spirit-equivalents, had an almost seven-fold increased risk (OR ¼ 6.8, 95% CI 1.4 -33.9), and drinking commencing at younger ages appears to carry a higher risk. An OR of 8.2 (95% CI 1.2 -57.4) was observed for those with GSTM1A, and GSTT1-null genotypes who had consumed a lifetime of 4250 kg of spirit-equivalents. In conclusion, alcohol consumption may increase breast cancer risk among those who carry susceptible GST genotypes.

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Section: Discussioncontrasting

confidence: 46%

Glutathione S-transferase M1 and T1 genetic polymorphisms, alcohol consumption and breast cancer risk

et al. 2003

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“…Mais especificamente em relação ao carcinoma mamário, os resultados são inconsistentes e heterogêneos 8,[11][12][13][14][15] . Chacko et al (2005), em estudo caso-controle com 224 mulheres indianas, não observaram associação entre deleção do GSTM1 e aumento significativo no risco de câncer de mama.…”

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“…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 . No entanto, ainda não está estabelecida a associação entre genótipos GSTM1 e GSTT1 e risco de desenvolvimento de carcinoma mamário 8,[11][12][13][14][15] .Sabe-se atualmente que o sistema GST também exerce papel importante no metabolismo dos estrogênios 3 . Dessa forma, pode-se supor que a menor atividade enzimática decorrente do genótipo nulo dos referidos genes poderia estar associada ao aumento da densidade mamária, o que se traduziria principalmente por padrão mamográfico denso [16][17][18] .…”

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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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“…Helzlsouer et al [14] and Charrier et al [24] reported positive associations for the GSTM1 null genotype and post-menopausal women, whereas Ambrosone et al [20] reported a positive association between null GSTM1 and younger pre-menopausal women. Helzlsouer et al [14] reported no association for GSTT1 null genotype and breast cancer in pre-or post-menopausal women, whereas GarciaClosas et al [22] observed an inverse association for GSTT1 null genotype among pre-menopausal women.…”

Section: Discussionmentioning

confidence: 99%

Prospective Case–Control Study to Evaluate the Role of Glutathione S Transferases (GSTT1 and GSTM1) Gene Deletion in Breast Carcinoma and Its Prognostic Significance

Bansal

Sharma

et al. 2014

Indian J Surg

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Breast cancer is the most common cause of cancer death in women with the incidence rising in young women. GST gene polymorphisms are significant because of their role in the detoxification of both environmental carcinogens and also cytotoxic drugs used in therapy for breast cancer. The present study has been designed to identify the role of polymorphisms in GSTT1 and GSTM1 genes in the risk of development of breast cancer, in the prognostication of breast cancer, and in the prediction of response towards chemotherapy. Ninety-nine patients with breast cancer and 100 healthy controls with no history of cancer were taken from blood donors after informed consent. Epidemiological and clinical data was collected from participants and 5 ml of peripheral venous blood was collected for genotype analysis. Null genotype of GSTT1 was detected in 51.04 % of the controls in comparison to 20.2 % of patients with carcinoma breast, which was found to be statistically significant (OR 4.18; 95 % CI 2.01-8.75; P=0.0001). GSTM1 gene deletion was also significantly more common among controls (60 %) than in patients with breast cancer (33 %) (OR 4.57; 95 % CI 2.20-9.51; P=0.0001). Tumors more than 5 cm in size had greater tendency for GSTM1 gene expression (P value=0.019), but other clinicopathological parameters did not show any correlation. GSTT1 and GSTM1 genes status did not show any association with response to chemotherapy. The results indicated the null genotype of both GSTT1 and GSTM1 to be protective for the development of carcinoma breast. None of the known etiological factors have any correlation with GSTT1 and GSTM1 gene deletion. Patients with small tumor size expressed GSTM1 gene deletion. Other tumor characteristics and clinicopathological parameters did not have any correlation with gene deletion.

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Allelotype influence at glutathione S-transferase M1 locus on breast cancer susceptibility

Cited by 42 publications

References 30 publications

Glutathione S-transferase M1 and T1 genetic polymorphisms, alcohol consumption and breast cancer risk

Glutathione S-transferase M1 and T1 genetic polymorphisms, alcohol consumption and breast cancer risk

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

Prospective Case–Control Study to Evaluate the Role of Glutathione S Transferases (GSTT1 and GSTM1) Gene Deletion in Breast Carcinoma and Its Prognostic Significance

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