RGD Reference Report - Association between severe toxicity of nilotinib and UGT1A1 polymorphisms in Japanese patients with chronic myelogenous leukemia. - Rat Genome Database

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Association between severe toxicity of nilotinib and UGT1A1 polymorphisms in Japanese patients with chronic myelogenous leukemia.

Authors: Shibata, T  Minami, Y  Mitsuma, A  Morita, S  Inada-Inoue, M  Oguri, T  Shimokata, T  Sugishita, M  Naoe, T  Ando, Y 
Citation: Shibata T, etal., Int J Clin Oncol. 2014 Apr;19(2):391-6. doi: 10.1007/s10147-013-0562-5. Epub 2013 Apr 23.
RGD ID: 10768829
Pubmed: PMID:23609856   (View Abstract at PubMed)
DOI: DOI:10.1007/s10147-013-0562-5   (Journal Full-text)

BACKGROUND: Nilotinib is a BCR-ABL kinase inhibitor approved for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia (CML). The UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphism UGT1A1*28 (*28)/*28 has been linked to an increased risk of hyperbilirubinemia in patients with CML who receive nilotinib. Beside *28, UGT1A1*6 (*6) is another important variant allele in Japanese patients because it is associated with adverse events of irinotecan, metabolized by UGT1A1. We retrospectively investigated the association between severe toxicity of nilotinib and UGT1A1 polymorphisms (*6 and*28) in Japanese patients with CML. PATIENTS AND METHODS: Eight patients with cytogenetically confirmed CML who were receiving nilotinib were studied to explore the association of UGT1A1 polymorphisms with severe nilotinib-related toxicity. Genotyping analyses were determined for *6 and *28. RESULTS: All 3 patients with the *6/*6 or *6/*28 genotype had severe toxicity, including QT interval prolongation (grade 3), elevated lipase levels (grade 3) plus hyperbilirubinemia (grade 2), and anemia (grade 3) plus hepatic cyst hemorrhage (grade 2) in 1 patient each. Among the 5 patients with the *6/*1 or *1/*1 genotype, 1 had elevated lipase levels (grade 3) and another had severe pain in the lower extremities (grade 3). CONCLUSION: These findings suggest that UGT1A1 polymorphisms are important determinants of severe toxicity of nilotinib in Japanese patients.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
myeloid leukemia treatmentIAGP 10768829DNA:polymorphism: :RGD 
myeloid leukemia treatmentISOUGT1A1 (Homo sapiens)10768829; 10768829DNA:polymorphism: :RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ugt1a1  (UDP glucuronosyltransferase family 1 member A1)

Genes (Mus musculus)
Ugt1a1  (UDP glucuronosyltransferase 1 family, polypeptide A1)

Genes (Homo sapiens)
UGT1A1  (UDP glucuronosyltransferase family 1 member A1)


Additional Information