MTHFR and VDR Polymorphisms Improve the Prognostic Value of MYCN Status on Overall Survival in Neuroblastoma Patients
Open Access
- 14 April 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (8), 2714
- https://doi.org/10.3390/ijms21082714
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.Funding Information
- Instituto de Salud Carlos III (PI13-00046)
This publication has 37 references indexed in Scilit:
- Activated ALK Collaborates with MYCN in Neuroblastoma PathogenesisCancer Cell, 2012
- Effect of ABCB1 and ABCC3 Polymorphisms on Osteosarcoma Survival after Chemotherapy: A Pharmacogenetic StudyPLOS ONE, 2011
- Methotrexate‐induced subacute neurotoxicity in a child with acute lymphoblastic leukemia carrying genetic polymorphisms related to folate homeostasisAmerican Journal of Hematology, 2010
- Randomized Trial of Prophylactic Granulocyte Colony-Stimulating Factor During Rapid COJEC Induction in Pediatric Patients With High-Risk Neuroblastoma: The European HR-NBL1/SIOPEN StudyJournal of Clinical Oncology, 2010
- A Mitochondrial Target Sequence Polymorphism in Manganese Superoxide Dismutase Predicts Inferior Survival in Breast Cancer Patients Treated with CyclophosphamideClinical Cancer Research, 2009
- The International Neuroblastoma Risk Group (INRG) Staging System: An INRG Task Force ReportJournal of Clinical Oncology, 2009
- The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force ReportJournal of Clinical Oncology, 2009
- Genotype of human carbonyl reductase CBR3 correlates with doxorubicin disposition and toxicityPharmacogenetics and Genomics, 2008
- A genome-wide approach to identify genetic variants that contribute to etoposide-induced cytotoxicityProceedings of the National Academy of Sciences of the United States of America, 2007
- Regularization and Variable Selection Via the Elastic NetJournal of the Royal Statistical Society Series B: Statistical Methodology, 2005