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The miR-1206 microRNA variant is associated with methotrexate-induced oral mucositis in pediatric acute lymphoblastic

Angela Gutierrez-Camino1, Natanja Oosterom, Marissa A H den Hoed

  • 1aDepartment of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursery bBioCruces Health Research Institute, University of the Basque Country (UPV/EHU), Leioa, Spain cPrincess Máxima Center for Pediatric Oncology, Utrecht dDepartment of Clinical Chemistry, Erasmus Medical Center eDepartment of Pediatric Oncology/Hematology, Erasmus Medical Center-Sophia's Children's Hospital, Rotterdam fDepartment of Clinical Chemistry, VU Medical Center, Amsterdam gDepartment of Pediatric Oncology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands hDepartment of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.

Pharmacogenetics and Genomics
|June 20, 2017
PubMed

Insights

Genetic variations in microRNA genes can predict methotrexate toxicity in children with acute lymphoblastic leukemia (ALL). Specifically, a variant in miR-1206 is linked to oral mucositis, offering a potential biomarker for personalized treatment strategies.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Pediatric acute lymphoblastic leukemia (ALL) survival rates are high (90%) in developed nations.
  • Methotrexate (MTX) chemotherapy frequently causes toxicity, including oral mucositis.
  • Genetic variations, particularly single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes, may influence MTX toxicity.

Purpose of the Study:

  • To replicate the association between specific miRNA variants and MTX-induced oral mucositis in a prospective pediatric ALL cohort.
  • To identify potential genetic biomarkers for predicting MTX toxicity in children undergoing ALL treatment.

Main Methods:

  • Genotyping of three SNPs (CNOT4 rs3812265, miR-1206 rs2114358, miR-2053 rs10505168) in 117 pediatric ALL patients.
  • Patients received 5 g/m² MTX as part of the DCOG ALL-10 protocol.
  • Oral mucositis was assessed using National Cancer Institute criteria (grade ≥3).

Main Results:

  • The SNP rs2114358 in miR-1206 was significantly associated with oral mucositis (Odds Ratio: 3.6; 95% Confidence Interval: 1.1-11.5).
  • No significant association was found for CNOT4 rs3812265 (OR: 0.69; 95% CI: 0.27-1.80) or miR-2053 rs10505168 (OR: 2.50; 95% CI: 0.76-8.24).
  • The findings replicate the link between miR-1206 genetic variation and MTX-induced oral mucositis.

Conclusions:

  • Genetic variation in miR-1206, specifically rs2114358, is confirmed as a predictor of MTX-induced oral mucositis in childhood ALL.
  • miR-1206 variants represent a promising novel biomarker for predicting MTX toxicity.
  • This finding supports the potential for personalized medicine approaches in pediatric ALL treatment to mitigate MTX-related side effects.

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