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

International Journal of Molecular Sciences

Jaime Font De Mora¹  Yania Yáñez¹  David Hervás²  Pablo Berlanga³  MiguelÁngel Sanz⁴  Pablo Gargallo⁵  Vanessa Segura⁵  Victoria Castel⁵  Adela Cañete⁵  GladysG. Olivera⁶  MaríaJosé Herrero⁶  Luis Sendra⁶  SalvadorF. Aliño⁶ 

[1] Clinical and Translational Research in Cancer, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain;Data Science, Biostatistics and Bioinformatics Platform, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain;Department of Pediatric and Adolescent Oncology, Institute Gustave Roussy Center, 94800 Villejuif, France;Hematology and Hemotherapy Service, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain;Pediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain;Pharmacogenetics Platform, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain;

关键词: pharmacogenetics;    neuroblastoma;    survival;    toxicity;    SNP;   

DOI  :  10.3390/ijms21082714

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown