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MTHFR and VDR Polymorphisms Improve the Prognostic Value of MYCN Status on Overall Survival in Neuroblastoma Patients.
Olivera, Gladys G; Yáñez, Yania; Gargallo, Pablo; Sendra, Luis; Aliño, Salvador F; Segura, Vanessa; Sanz, Miguel Ángel; Cañete, Adela; Castel, Victoria; Font De Mora, Jaime; Hervás, David; Berlanga, Pablo; Herrero, María José.
Affiliation
  • Olivera GG; Pharmacogenetics Platform, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
  • Yáñez Y; Department of Pharmacology, University of Valencia, 46010 Valencia, Spain.
  • Gargallo P; Clinical and Translational Research in Cancer, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
  • Sendra L; Pediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain.
  • Aliño SF; Pharmacogenetics Platform, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
  • Segura V; Department of Pharmacology, University of Valencia, 46010 Valencia, Spain.
  • Sanz MÁ; Pharmacogenetics Platform, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
  • Cañete A; Department of Pharmacology, University of Valencia, 46010 Valencia, Spain.
  • Castel V; Clinical Pharmacology Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain.
  • Font De Mora J; Pediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain.
  • Hervás D; Hematology and Hemotherapy Service, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain.
  • Berlanga P; Pediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain.
  • Herrero MJ; Pediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain.
Int J Mol Sci ; 21(8)2020 Apr 14.
Article in En | MEDLINE | ID: mdl-32295184
Single nucleotide polymorphisms (SNPs) in Pharmacogenetics can play an important role in the outcomes of the chemotherapy treatment in Neuroblastoma, helping doctors maximize efficacy and minimize toxicity. Employing AgenaBioscience MassArray, 96 SNPs were genotyped in 95 patients looking for associations of SNP with response to induction therapy (RIT) and grade 3-4 toxicities, in High Risk patients. Associations of SNPs with overall (OS) and event-free (EFS) survival in the whole cohort were also explored. Cox and logistic regression models with Elastic net penalty were employed. Association with grade 3-4 gastrointestinal and infectious toxicities was found for 8 different SNPs. Better RIT was correlated with rs726501 AG, rs3740066 GG, rs2010963 GG and rs1143684 TT (OR = 2.87, 1.79, 1.23, 1.14, respectively). EFS was affected by rs2032582, rs4880, rs3814058, rs45511401, rs1544410 and rs6539870. OS was influenced by rs 1801133, rs7186128 and rs1544410. Remarkably, rs1801133 in MTHFR (p = 0.02) and rs1544410 in VDR (p = 0.006) also added an important predictive value for OS to the MYCN status, with a more accurate substratification of the patients. Although validation studies in independent cohorts will be required, the data obtained supports the utility of Pharmacogenetics for predicting Neuroblastoma treatment outcomes.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers, Tumor / Receptors, Calcitriol / Methylenetetrahydrofolate Reductase (NADPH2) / N-Myc Proto-Oncogene Protein / Neuroblastoma Type of study: Prognostic_studies Limits: Humans Language: En Journal: Int J Mol Sci Year: 2020 Document type: Article Affiliation country: Spain Country of publication: Switzerland

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers, Tumor / Receptors, Calcitriol / Methylenetetrahydrofolate Reductase (NADPH2) / N-Myc Proto-Oncogene Protein / Neuroblastoma Type of study: Prognostic_studies Limits: Humans Language: En Journal: Int J Mol Sci Year: 2020 Document type: Article Affiliation country: Spain Country of publication: Switzerland