TY - JOUR
T1 - The miR-1206 microRNA variant is associated with methotrexate-induced oral mucositis in pediatric acute lymphoblastic leukemia
AU - Gutierrez-Camino, Angela
AU - Oosterom, Natanja
AU - den Hoed, Marissa A H
AU - Lopez-Lopez, Elixabet
AU - Martin-Guerrero, Idoia
AU - Pluijm, Saskia M F
AU - Pieters, Rob
AU - de Jonge, Robert
AU - Tissing, Wim J E
AU - Heil, Sandra G
AU - García-Orad, Africa
AU - van den Heuvel-Eibrink, Marry M
N1 - Publisher Copyright:
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2017/8
Y1 - 2017/8
N2 - Five-year survival rates of pediatric acute lymphoblastic leukemia (ALL) have reached 90% in the developed countries. However, toxicity because of methotrexate (MTX) occurs frequently. Variety in the occurrence of toxicity is partly determined by single nucleotide polymorphisms (SNPs) in coding regions. Recently, five SNPs in non-coding pre-microRNAs and microRNA processing (miRNA) genes were identified in association with MTX-induced oral mucositis. This study aimed to replicate the association of these miRNA variants in relation to MTX-induced oral mucositis in a prospective childhood ALL cohort. Three out of five SNPs with a minor allele frequency more than 0.15 [CCR4-NOT transcription complex (CNOT4) rs3812265, miR-1206 rs2114358, miR-2053 rs10505168] were analyzed in 117 pediatric ALL patients treated with 5 g/m MTX (DCOG ALL-10). Oral mucositis was defined as grade more than or equal to 3 according to the National Cancer Institute criteria. rs2114358 in miR-1206 was associated with oral mucositis [odds ratio (OR): 3.6; 95% confidence interval (CI): 1.1-11.5], whereas we did not confirm the association of CNOT4 rs3812265 (OR: 0.69; 95% CI: 0.27-1.80) and miR-2053 rs10505168 (OR: 2.50; 95% CI: 0.76-8.24). Our results replicate the association between rs2114358 in miR-1206 and MTX-induced oral mucositis in childhood ALL. Genetic variation in miR-1206 has potential as a novel biomarker to predict MTX-induced toxicity.
AB - Five-year survival rates of pediatric acute lymphoblastic leukemia (ALL) have reached 90% in the developed countries. However, toxicity because of methotrexate (MTX) occurs frequently. Variety in the occurrence of toxicity is partly determined by single nucleotide polymorphisms (SNPs) in coding regions. Recently, five SNPs in non-coding pre-microRNAs and microRNA processing (miRNA) genes were identified in association with MTX-induced oral mucositis. This study aimed to replicate the association of these miRNA variants in relation to MTX-induced oral mucositis in a prospective childhood ALL cohort. Three out of five SNPs with a minor allele frequency more than 0.15 [CCR4-NOT transcription complex (CNOT4) rs3812265, miR-1206 rs2114358, miR-2053 rs10505168] were analyzed in 117 pediatric ALL patients treated with 5 g/m MTX (DCOG ALL-10). Oral mucositis was defined as grade more than or equal to 3 according to the National Cancer Institute criteria. rs2114358 in miR-1206 was associated with oral mucositis [odds ratio (OR): 3.6; 95% confidence interval (CI): 1.1-11.5], whereas we did not confirm the association of CNOT4 rs3812265 (OR: 0.69; 95% CI: 0.27-1.80) and miR-2053 rs10505168 (OR: 2.50; 95% CI: 0.76-8.24). Our results replicate the association between rs2114358 in miR-1206 and MTX-induced oral mucositis in childhood ALL. Genetic variation in miR-1206 has potential as a novel biomarker to predict MTX-induced toxicity.
KW - Adolescent
KW - Antimetabolites, Antineoplastic/administration & dosage
KW - Child
KW - Child, Preschool
KW - Female
KW - Gene Frequency
KW - Genetic Association Studies
KW - Humans
KW - Infant
KW - Male
KW - Methotrexate/administration & dosage
KW - MicroRNAs/chemistry
KW - Nucleic Acid Conformation
KW - Polymorphism, Single Nucleotide
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
KW - Prospective Studies
KW - Stomatitis/chemically induced
UR - http://www.scopus.com/inward/record.url?scp=85021096806&partnerID=8YFLogxK
U2 - 10.1097/FPC.0000000000000291
DO - 10.1097/FPC.0000000000000291
M3 - Article
C2 - 28628559
SN - 1744-6872
VL - 27
SP - 303
EP - 306
JO - Pharmacogenetics and genomics
JF - Pharmacogenetics and genomics
IS - 8
ER -