Aim: Hepatotoxicity is one of the most common drug-related toxicities during the treatment of childhood acute lymphoblastic leukemia (ALL). Many genes involved in liver-specific signaling pathways are tightly controlled by miRNAs, and miRNA function could be modulated by SNPs. As a consequence, we hypothesized that variants in miRNAs could be associated with drug-induced hepatotoxicity.
Methods: We analyzed 213 SNPs in 206 miRNAs in a cohort of 179 children with ALL homogeneously treated.
Results: rs2648841 in miR-1208 was the most significant SNP during consolidation phase after false discovery rate correction, probably through an effect on its target genes DHFR, MTR and MTHFR.
Conclusion: These results point out the possible involvement of SNPs in miRNAs in toxicity to chemotherapy in children with ALL.
Keywords: SNPs; chemotherapy; childhood acute lymphoblastic leukemia; hepatotoxicity; methotrexate; miRNAs.