Polymorphisms at microRNA binding sites of Ara-C and anthracyclines-metabolic pathway genes are associated with outcome of acute myeloid leukemia patients.

Abstract

BACKGROUND:

Gene polymorphisms at microRNA-binding sites (poly-miRTS) may affect gene transcription and expression through miRNA regulation, which is associated with cancer susceptibility, sensitivity to chemotherapy and prognosis. This study investigated the association between poly-miRTS of Ara-C/anthracycline metabolic pathways genes and the outcome of acute myeloid leukemia (AML) in Chinese patients after Ara-C-based chemotherapy.

METHODS:

A total of 17 poly-miRTS were selected from the SNPinfo Web Server and genotyped in 206 Chinese Han non-FAB-M3 AML patients using the SEQUENOM Mass-ARRAY system.

RESULTS:

Among these 17 poly-miRTS, five Ara-C metabolic gene single nucleotide polymorphisms (SNPs, NT5C2 rs10786736 and rs8139, SLC29A1 rs3734703, DCTD rs7278, and RRM1 rs1042919) were identified to significantly associate with complete AML remission and/or overall and relapse-free survival (OS and RFS, respectively), and four anthracycline-metabolic gene SNPs (ABCC1 rs3743527, rs212091, and rs212090 and CBR1 rs9024) were significantly associated with chemotherapy-related toxicities. Moreover, SLC29A1 rs3734703 was shown to associate with both chemotherapy response and survival (adjusted OR 2.561 in the overdominant model; adjusted HR 2.876 for OS and 2.357 for RFS in the dominant model).

CONCLUSIONS:

The data from the current study demonstrated that the poly-miRTS of Ara-C/anthracyclines metabolic genes predicted the sensitivity and side effects of AML to Ara-C-based chemotherapy and patient survival. Further study will confirm them as biomarkers for AML patients after Ara-C-based chemotherapy.

• Authors: Hai-Xia Cao, Chao-Feng Miao, Liang Yan, Ping Tang, Li-Rong Zhang, Ling Sun
• Journal: Journal of translational medicine (J Transl Med) Vol. 15 Issue 1 Pg. 235 (Nov 15 2017) ISSN: 1479-5876 [Electronic] England
• PMID: 29141648 (Publication Type: Journal Article)

Chemical References

• Anthracyclines
• Biomarkers, Tumor
• MicroRNAs
• Cytarabine

Topics

• Adolescent
• Adult
• Aged
• Anthracyclines (administration & dosage, pharmacokinetics)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Binding Sites (genetics)
• Biomarkers, Tumor (genetics)
• Cytarabine (administration & dosage, metabolism)
• Female
• Follow-Up Studies
• Genetic Predisposition to Disease
• Humans
• Inactivation, Metabolic (genetics)
• Leukemia, Myeloid, Acute (diagnosis, drug therapy, genetics, mortality)
• Male
• Metabolic Networks and Pathways (genetics)
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Polymorphism, Single Nucleotide
• Prognosis
• Remission Induction
• Survival Analysis
• Treatment Outcome
• Young Adult