Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer

Lizard-Nacol, Sarab; Coudert, Bruno; Colosetti, Pascal; Riedinger, Jean-Marc; Fargeot, P.; Brunet‐Lecomte, Patrick

doi:10.1186/bcr17

Cited by 49 publications

(37 citation statements)

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“…27 When GSTP1 genotype was analyzed as a trichotomous variable, an allele-related dosage effect was found, with increasing variant allelic character being associated with improved postchemotherapy survival. No associations between GSTM1 or GSTT1 deletion and various tumor characteristics, including TNM status, were observed in the current study or in other previously conducted studies, 12,13,28 suggesting that GSTM1 and GSTT1 activity may not play a role in breast carcinoma progression. Furthermore, we did not find overall survival to be associated with single or combined deletions in GSTM1 and/or GSTT1 in patients with breast carcinoma after chemotherapy.…”

Section: Discussioncontrasting

confidence: 47%

“…The results of such studies have been mixed. [12][13][14][15][16] Ambrosone et al 13 and Sweeney et al 14 found that clinical outcomes after chemotherapy were significantly associated with certain GST polymorphisms, whereas no effect was reported in other studies. 12,16 Studies of different populations, and particularly larger cohorts, clearly are needed.…”

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confidence: 99%

“…[12][13][14][15][16] Ambrosone et al 13 and Sweeney et al 14 found that clinical outcomes after chemotherapy were significantly associated with certain GST polymorphisms, whereas no effect was reported in other studies. 12,16 Studies of different populations, and particularly larger cohorts, clearly are needed. In the current study, we evaluated overall survival in association with polymorphisms in the GSTM1, GSTT1, and GSTP1 genes in 1034 Chinese patients who were treated with chemotherapy for primary invasive breast carcinoma between 1996 and 1998 and who were followed for a median of 5.3 years.…”

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Genetic polymorphisms in glutathione‐S‐transferase genes (GSTM1, GSTT1, GSTP1) and survival after chemotherapy for invasive breast carcinoma

Yang

Shu

Ruan

et al. 2004

Cancer

102

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BACKGROUNDIt has been suggested that genetic polymorphisms in certain glutathione‐S‐transferase (GST) genes reduce the effectiveness of detoxifying cytotoxins generated by chemotherapeutic agents, potentially resulting in enhanced clinical responses to chemotherapy.METHODSThe authors evaluated common polymorphisms in the GSTM1, GSTT1, and GSTP1 genes for associations with overall survival in 1034 patients with invasive breast carcinoma who were recruited into the Shanghai Breast Cancer Study between 1996 and 1998, treated with chemotherapy, and followed for a median of 5.3 years.RESULTSAfter adjusting for age, tumor stage, and the use of radiotherapy and tamoxifen, women who were homozygous for the variant GSTP1 105Val allele had a 60% reduction in mortality risk compared with women who were homozygous for the Ile allele (hazard ratio, 0.4; 95% confidence interval, 0.2–0.8). No association was found with respect to any of the GSTM1 or GSTT1 genotypes.CONCLUSIONSThe results of the current study indicate a potential role for GSTP1 polymorphism in predicting the clinical outcomes of patients with breast carcinoma who are treated with chemotherapy. Cancer 2005. © 2004 American Cancer Society.

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Section: Discussioncontrasting

confidence: 47%

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confidence: 99%

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Genetic polymorphisms in glutathione‐S‐transferase genes (GSTM1, GSTT1, GSTP1) and survival after chemotherapy for invasive breast carcinoma

Yang

Shu

Ruan

et al. 2004

Cancer

102

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“…Dados recentes têm revelado aumento da incidência 22 . Estudos epidemiológicos sugerem que fatores ambientais devem contribuir para esse aumento 4 e que diferenças genéticas podem também estar associadas a variações individuais na susceptibilidade ao câncer de mama 5 . Dentre os aspectos genéticos, 10% a 15% dos cânceres de mama têm história familiar positiva para a doença, sendo que apenas 5% podem ser explicados pelas raras, mas de grande penetrância, mutações genéticas BRCA1 e BRCA2 23 .…”

Section: Discussionunclassified

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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“…There have been only a few studies of GST genetic polymorphism and survival after treatment of breast carcinoma (Lizard-Nacol et al, 1999;Ambrosone et al, 2001). For the most part, prior studies were undertaken on a small or heterogeneous population.…”

Section: Discussionmentioning

confidence: 99%

Glutathione S-transferases (GSTT1 and GSTM1) gene deletions in Tunisians: susceptibility and prognostic implications in breast carcinoma

et al. 2003

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Glutathione S-transferase Theta1 and Mu1 (GSTT1 and GSTM1) are involved in the metabolism and detoxification of a wide range of potential environmental carcinogens. Conversely, they contribute to tumour cell survival by detoxification of numerous products induced by cancer therapy. The authors designed a large study to investigate the susceptibility and prognostic implications of the GSTT1 and GSTM1 gene deletions in breast carcinoma. The authors used the polymerase chain reaction to characterise the variation of the GSTT1 and GSTM1 genes in 309 unrelated Tunisian patients with breast carcinoma and 242 healthy control subjects. Associations of the clinic-pathologic parameters and the genetic markers with the rates of the breast carcinoma specific overall survival (OVS) and the disease-free survival (DFS) were assessed using univariate and multivariate analyses. A significant association was found between gene deletion of GSTT1 and the risk of early onset of breast carcinoma (OR ¼ 1.60, P ¼ 0.02). The lack of GSTT1 gene deletion was significantly associated with poor clinical response to chemotherapy (OR ¼ 2.29, P ¼ 0.03). This association was significantly higher in patients with axillary's lymph node-negative breast carcinoma (OR ¼ 12.60, P ¼ 0.005). The null-GSTT1 genotype showed a significant association with increased DFS in this selected population of patients. This association was even higher in patients carrying both null-GSTT1 and -GSTM1 genotypes. The gene deletion of GSTs may predict not only the early onset of breast carcinoma but also the clinical response to chemotherapy and the recurrence-free survival for patients with lymph nodenegative breast carcinoma.

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Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer

Abstract: http://breast-cancer-research.com/vol1no1/01sep99/research/2

Cited by 49 publications

References 21 publications

Genetic polymorphisms in glutathione‐S‐transferase genes (GSTM1, GSTT1, GSTP1) and survival after chemotherapy for invasive breast carcinoma

Genetic polymorphisms in glutathione‐S‐transferase genes (GSTM1, GSTT1, GSTP1) and survival after chemotherapy for invasive breast carcinoma

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

Glutathione S-transferases (GSTT1 and GSTM1) gene deletions in Tunisians: susceptibility and prognostic implications in breast carcinoma

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