title: Do genetic polymorphisms modulate response rate and toxicity of Cisplatin associated with radiotherapy in laryngeal squamous cell carcinoma?: a case report.
abstract: Cisplatin (CDDP) plus radiotherapy (RT) has been used to treat advanced laryngeal squamous cell carcinoma (LSCC) patients. Single nucleotide polymorphisms (SNPs) may be responsible for differences in chemo/radiosensitivity and side effects in those patients. We reported an advanced LSCC patient, who obtained durable complete response and unexpected pronounced toxicity during CDDP and RT, possibly due to SNPs in genes that modulate the effects of this therapeutic modality.
  
  
  METHODS
  A 30-year-old man with advanced LSCC obtained durable complete response and severe alopecia and pancytopenia after standard and reduced doses of CDDP and RT. Analyses of SNPs revealed that the patient presented GSTT1 deletion, variant MSH3 1045ThrThr, wild GSTP1 105IleIle, and wild BAX -248GG genotypes, which were previously described in association with abnormal detoxification, DNA repair, and damaged cell apoptosis, respectively. Seven other advanced LSCC patients with GSTT1 gene, MSH3 AlaAla or AlaThr, GSTP1 IleVal or ValVal, and BAX GA or AA genotypes served as controls of the study. Only 1 control presented complete response; the other 6 controls obtained partial response of short duration. Four and 3 controls presented grade 1 or 2 and grade 3 anemia or leukopenia during treatment, respectively. The CDDP level in urine collected after CDDP infusion in the reported patient was lower than the median value obtained in controls, suggesting a higher amount of intracellular CDDP in the reported case.The data suggest, for the first time, that inherited abnormalities in intracellular detoxification of CDDP, DNA repair of lesions induced by CDDP and RT, and damaged cell apoptosis may alter treatment response and toxicity in LSCC, but should be confirmed by large pharmacogenomic studies.
authors.affiliation: From the Department of Internal Medicine (LLA, CMLN, EFDC, GASN, TRPL, ECP, CSPL); Department of Clinical Pathology Brazil (MBV, PM); and Department of Radiology (JMCA), Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Leisa
authors.initials: L
authors.lastname: Lopes-Aguiar
authors.forename: Marília Berlofa
authors.initials: MB
authors.lastname: Visacri
authors.forename: Carolina Marques Lopes
authors.initials: CML
authors.lastname: Nourani
authors.forename: Ericka Francislaine Dias
authors.initials: EFD
authors.lastname: Costa
authors.forename: Guilherme Augusto Silva
authors.initials: GAS
authors.lastname: Nogueira
authors.forename: Tathiane Regine Penna
authors.initials: TRP
authors.lastname: Lima
authors.forename: Eder Carvalho
authors.initials: EC
authors.lastname: Pincinato
authors.forename: Patrícia
authors.initials: P
authors.lastname: Moriel
authors.forename: João Maurício Carrasco
authors.initials: JMC
authors.lastname: Altemani
authors.forename: Carmen Silvia Passos
authors.initials: CSP
authors.lastname: Lima
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000628:therapy*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012074:Remission Induction; D000077195:Squamous Cell Carcinoma of Head and Neck; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494826:BAX protein, human; D051028:bcl-2-Associated X Protein; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D002945:Cisplatin