MTHFR and VDR Polymorphisms Improve the Prognostic Value of MYCN Status on Overall Survival in Neuroblastoma Patients

Autores de IIS La Fe

• Gladys Guadalupe Olivera Pasquini

  Autor

• Yania Yañez Peralta

  Autor

• Pablo Gargallo Tatay

  Autor

• Luis Sendra Gisbert

  Autor

• Salvador F Aliño Pellicer

  Autor

• Vanessa Segura Caballer

  Autor

• Miguel Ángel Sanz Alonso

  Autor

• Adela Cañete Nieto

  Autor

• Victoria Castel Sánchez

  Autor

• Jaime Font De Mora Sainz

  Autor

• David Hervás Marín

  Autor

• Pablo Berlanga Charriel

  Autor

• María José Herrero Cervera

  Autor

Grupos

• Farmacogenética

• Hematología y Hemoterapia

• Investigación Clínica y Traslacional en Cáncer

Abstract

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.

Keywords

• pharmacogenetics; neuroblastoma; survival; toxicity; SNP