Association between SLCO1B1 rs4149056 and tegafur-uracil-induced hepatic dysfunction in breast cancer

The aim of this study was to identify pharmacogenomic biomarkers to predict tegafur-uracil (UFT)-induced liver dysfunction.  A total of 68 patients, who were administered UFT, were evaluated using a two-step pharmacogenomics analysis. The first screening revealed the association between five SNPs an...

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Bibliographic Details
Published in:Pharmacogenomics 2019-04, Vol.20 (5), p.353-365
Main Authors: Kamio, Hidenori, Uchiyama, Toshitaka, Kanno, Hitoshi, Onoe, Yoshiko, Saito, Kayoko, Kameoka, Shingo, Kamio, Takako, Okamoto, Takahiro
Format: Article
Language:English
Subjects:
Age
Aged
Alanine
Alanine transaminase
Alanine Transaminase - blood
Aspartate aminotransferase
Aspartate Aminotransferases - blood
Biomarkers
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Chemical and Drug Induced Liver Injury - genetics
Chemical and Drug Induced Liver Injury - metabolism
Chemotherapy
Colorectal cancer
Drug Combinations
Drug dosages
Endocrine therapy
Enzymes
Female
Genetic Predisposition to Disease
Genomics
Haplotypes
Humans
Liver
Liver diseases
Liver-Specific Organic Anion Transporter 1 - genetics
Liver-Specific Organic Anion Transporter 1 - metabolism
Metabolism
Middle Aged
Pharmacogenomic Testing
Pharmacogenomics
Polymorphism, Single Nucleotide
Polypeptides
Single-nucleotide polymorphism
Studies
Tegafur
Tegafur - administration & dosage
Tegafur - adverse effects
Transaminase
Uracil
Uracil - administration & dosage
Uracil - adverse effects
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Summary:The aim of this study was to identify pharmacogenomic biomarkers to predict tegafur-uracil (UFT)-induced liver dysfunction.  A total of 68 patients, who were administered UFT, were evaluated using a two-step pharmacogenomics analysis. The first screening revealed the association between five SNPs and UFT-induced hepatic dysfunction. In the second step, (rs4149056) was found to be the only SNP associated with UFT treatment-related elevation of aspartate aminotransferase (odds ratio: C/C vs T/T = 7.8, C/T vs T/T = 5.7; p = 0.037) and alanine transaminase (odds ratio: C/C vs T/T = 12.2, C/T vs T/T = 4.1; p = 0.034) levels.  The  polymorphisms are possible predictors of UFT treatment-related hepatic dysfunction.
ISSN:1462-2416
1744-8042
DOI:10.2217/pgs-2018-0100