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GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms in outcomes of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation.
Pincinato, Eder C; Costa, Ericka F D; Lopes-Aguiar, Leisa; Nogueira, Guilherme A S; Lima, Tathiane R P; Visacri, Marília B; Costa, Anna P L; Lourenço, Gustavo J; Calonga, Luciane; Mariano, Fernanda V; Altemani, Albina M A M; Coutinho-Camillo, Cláudia; Chone, Carlos T; Ramos, Celso D; Altemani, João M C; Moriel, Patrícia; Lima, Carmen S P.
Afiliación
  • Pincinato EC; Clinical Oncology Service, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
  • Costa EFD; Health and Biological Science Center, Faculty of Pharmacy, Mackenzie Presbyterian University, São Paulo, São Paulo, Brazil.
  • Lopes-Aguiar L; Clinical Oncology Service, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
  • Nogueira GAS; Clinical Oncology Service, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
  • Lima TRP; Clinical Oncology Service, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
  • Visacri MB; Clinical Oncology Service, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
  • Costa APL; Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
  • Lourenço GJ; Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
  • Calonga L; Laboratory of Cancer Genetics, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
  • Mariano FV; Department of Ophthalmology and Otolaryngology, School of Medical Sciences, University of Campinas, University of Campinas, Campinas, São Paulo, Brazil.
  • Altemani AMAM; Department of Pathology, School of Medical Sciences, University of Campinas, São Paulo, Brazil.
  • Coutinho-Camillo C; Department of Pathology, School of Medical Sciences, University of Campinas, São Paulo, Brazil.
  • Chone CT; A. C. Camargo Cancer Center, São Paulo, São Paulo, Brazil.
  • Ramos CD; Department of Ophthalmology and Otolaryngology, School of Medical Sciences, University of Campinas, University of Campinas, Campinas, São Paulo, Brazil.
  • Altemani JMC; Department of Radiology, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
  • Moriel P; Department of Radiology, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
  • Lima CSP; Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
Sci Rep ; 9(1): 9312, 2019 06 27.
Article en En | MEDLINE | ID: mdl-31249357
Cisplatin (CDDP) combined with radiotherapy (RT) is employed in head and neck squamous cell carcinoma (HNSCC) with variable toxicities and clinical response. Glutathione S-transferases (GSTs) participate in CDDP excretion from cells, and genes encoding GSTs, GSTM1, GSTT1and GSTP1, are polymorphic in humans. This prospective study aimed to evaluate the roles of GSTM1, GSTT1, and GSTP1 Ile105Val polymorphisms in outcomes of HNSCC patients treated with CDDP chemoradiation. Ninety patients were genotyped by multiplex PCR. Urinary CDDP measurements were performed by HPLC. Treatment side effects and response were analysed by conventional criteria. Patients with GSTT1 genes showed 7.23- and 5.37-fold higher likelihood of presenting vomiting and ototoxicity, lower glomerular filtration rate (GFR), and lower elimination of CDDP in urine relative to patients with deleted genes. Patients harbouring the GSTP1 IleVal or ValVal genotypes showed 4.28-fold higher likelihood of presenting grade 2 or 3 vomiting and lower GFR with treatment than those harbouring the IleIle genotype. In multivariate Cox analysis, patients with the GSTP1 105ValVal genotype had 3.87 more chance of presenting disease progression than those with the IleIle or IleVal genotype (p < 0.01). Our findings provide preliminary evidence that inherited abnormalities in CDDP metabolism, related to GSTT1 and GSTP1 Ile105Val polymorphisms, alter outcomes of HNSCC patients treated with CDDP and RT.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Gutatión-S-Transferasa pi / Quimioradioterapia / Carcinoma de Células Escamosas de Cabeza y Cuello / Glutatión Transferasa Tipo de estudio: Observational_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Gutatión-S-Transferasa pi / Quimioradioterapia / Carcinoma de Células Escamosas de Cabeza y Cuello / Glutatión Transferasa Tipo de estudio: Observational_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido