SLCO1B1 Polymorphisms are Associated With Drug Intolerance in Childhood Leukemia Maintenance Therapy
| Autor: | Hilal Özdağ, N. Lale Şatiroğlu-Tufan, Elif İnce, Recep Bindak, Mehmet Ertem, Ozge Cumaogullari, İrem Eldem, L. Zümrüt Uysal, Talia Ileri, Beyza Doğanay Erdoğan, Duygu Yavuz |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Male medicine.medical_specialty Childhood leukemia Turkey Drug intolerance Polymorphism Single Nucleotide Maintenance Chemotherapy 03 medical and health sciences 0302 clinical medicine Maintenance therapy Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Child Thiopurine methyltransferase biology business.industry Liver-Specific Organic Anion Transporter 1 Infant Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Neoplasm Proteins 030104 developmental biology 030220 oncology & carcinogenesis Methylenetetrahydrofolate reductase Child Preschool Pediatrics Perinatology and Child Health biology.protein Female ITPA business SLCO1B1 Pharmacogenetics |
| Zdroj: | Journal of pediatric hematology/oncology. 40(5) |
| ISSN: | 1536-3678 |
| Popis: | BACKGROUND Therapy discontinuations and toxicities occur because of significant interindividual variations in 6-mercaptopurine (6-MP) and methotrexate (MTX) response during maintenance therapy of childhood acute lymphoblastic leukemia (ALL). 6-MP/MTX intolerance in some of the patients cannot be explained by thiopurine S-methyl transferase (TPMT) gene variants. In this study, we aimed to investigate candidate pharmacogenetic determinants of 6-MP and MTX intolerance in Turkish ALL children. METHODS In total, 48 children with ALL who had completed or were receiving maintenance therapy according to Children's Oncology Group (COG) protocols were enrolled. Fifteen single-nucleotide polymorphisms in 8 candidate genes that were related to drug toxicity or had a role in the 6-MP/MTX metabolism (TPMT, ITPA, MTHFR, IMPDH2, PACSIN2, SLCO1B1, ABCC4, and PYGL) were genotyped by competitive allele-specific PCR (KASP). Drug doses during maintenance therapy were modified according to the protocol. RESULTS The median drug dose intensity was 50% (28% to 92%) for 6-MP and 58% (27% to 99%) for MTX in the first year of maintenance therapy, which were lower than that scheduled in all patients. Among the analyzed polymorphisms, variant alleles in SLCO1B1 rs4149056 and rs11045879 were found to be associated with lower 6-MP/MTX tolerance. CONCLUSIONS SLCO1B1 rs4149056 and rs11045879 polymorphisms may be important genetic markers to individualize 6-MP/MTX doses. |
| Databáze: | OpenAIRE |
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