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

• Published in: International journal of molecular sciences Vol. 21; no. 8; p. 2714
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.04.2020; MDPI
• Subjects: Age; Alleles; Biomarkers, Tumor; Chemotherapy; Drug dosages; Gene Frequency; Genes; Genomes; Genotype; Hospitals; Humans; Induction therapy; Medical prognosis; Metastasis; Methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; N-Myc Proto-Oncogene Protein - genetics; Neuroblastoma; Neuroblastoma - genetics; Neuroblastoma - mortality; Nucleotides; Patients; Pharmacogenetics; Pharmacology; Prognosis; Receptors, Calcitriol - genetics; Regression analysis; Single-nucleotide polymorphism; SNP; Survival; Survival Analysis; Toxicity; Transcription factors; Tumors; toxicity; neuroblastoma; SNP; pharmacogenetics; survival
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21082714

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 ( = 0.02) and rs1544410 in ( = 0.006) also added an important predictive value for OS to the 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.