CYP1A2*1C, CYP2E1*5B, and GSTM1 polymorphisms are predictors of risk and poor outcome in head and neck squamous cell carcinoma patients

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorRibeiro Olivieri, Eloisa Helena-
Autor(es): dc.creatorda Silva, Sabrina Daniela-
Autor(es): dc.creatorMendonca, Fernando Fernandes-
Autor(es): dc.creatorUrata, Yuri Nagamine-
Autor(es): dc.creatorVidal, Daniel Onofre-
Autor(es): dc.creatorMedrado Faria, Marcilia de Araujo-
Autor(es): dc.creatorNishimoto, Ines Nobuko-
Autor(es): dc.creatorRainho, Claudia Aparecida-
Autor(es): dc.creatorKowalski, Luiz Paulo-
Autor(es): dc.creatorRogatto, Silvia Regina-
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Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionProcesso FAPESP: 04/00639-2-
Descrição: dc.descriptionProcesso CEPID/FAPESP: 98/14335-
Descrição: dc.descriptionHead and neck squamous cell carcinoma (HNSCC) is associated with environmental factors, especially tobacco and alcohol consumption. Most of the carcinogens present in tobacco smoke are converted into DNA-reactive metabolites by cytochrome P450 (CYPs) enzymes and detoxification of these substances is performed by glutathione S-transferases (GSTs). It has been suggested that genetic alterations, such as polymorphisms, play an important role in tumorigenesis and HNSCC progression. The aim of this study was to investigate CYP1A1, CYP1A2, CYP2E1, GSTM1, and GSTT1 polymorphisms as risk factors in HNSCC and their association with clinicopathologic data. The patients comprised 153 individuals with HNSCC (cases) and 145 with no current or previous diagnosis of cancer (controls). Genotyping of the single nucleotide polymorphisms (SNPs) of the CYP1A1, CYP1A2, and CYP2E1 genes was performed by PCR-RFLP and the GSTM1 and GSTT1 copy number polymorphisms (CNPs) were analyzed by PCR-multiplex. As expected, a significant difference was detected for tobacco and alcohol consumption between cases and controls (P < 0.001). It was observed that the CYP1A2*1D (OR = 16.24) variant and GSTM1 null alleles (OR = 0.02) confer increased risk of HNSCC development (P < 0.001). In addition, head and neck cancer alcohol consumers were more frequently associated with the CYP2E1*5B variant allele than control alcohol users (P < 0.0001, OR = 190.6). The CYP1A2*1C polymorphism was associated with tumor recurrence (log-rank test, P = 0.0161). The CYP2E1*5B and GSTM1 null alleles were significantly associated with advanced clinical stages (T3 + T4; P = 0.022 and P = 0.028, respectively). Overall, the findings suggested that the genetic polymorphisms studied are predictors of risk and are also associated with tumor recurrence, since they are important for determining the parameters associated with tumor progression and poor outcomes in HNSCC. (C) 2009 Elsevier Ltd. All rights reserved.-
Formato: dc.formatE73-E79-
Idioma: dc.languageen-
Publicador: dc.publisherElsevier B.V.-
Relação: dc.relationOral Oncology-
Relação: dc.relation4.636-
Relação: dc.relation1,912-
Direitos: dc.rightsclosedAccess-
Palavras-chave: dc.subjectCytochrome P450-
Palavras-chave: dc.subjectGlutathione S-transferases-
Palavras-chave: dc.subjectGenetic polymorphisms-
Palavras-chave: dc.subjectHead and neck squamous cell carcinoma-
Palavras-chave: dc.subjectClinical outcome-
Título: dc.titleCYP1A2*1C, CYP2E1*5B, and GSTM1 polymorphisms are predictors of risk and poor outcome in head and neck squamous cell carcinoma patients-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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