Pharmacogenetics of ABCB5, ABCC5 and RLIP76 and doxorubicin pharmacokinetics in Asian breast cancer patients
Abstract
This study investigated the impact of ABCB5, ABCC5 and RLIP76 polymorphisms on doxorubicin pharmacokinetics in Asian breast cancer patients (N=62). Direct sequencing was performed to screen for previously identified ABCC5 polymorphisms as well as polymorphisms in the exons and exon-intron boundaries of ABCB5 and RLIP76 genes. Genotype-phenotype correlations were analyzed using Mann-Whitney U-test. The homozygous variant allele at the ABCC5 g.+7161G>A (rs1533682) locus was significantly associated with higher doxorubicin clearance (g.+7161AA vs g.+7161GG, CL/BSA (Lh -1 m -2 ): 30.34 (25.41-33.60) vs 22.46 (15.04-49.4), P=0.04). Homozygosity for the reference allele at the ABCC5 g.-1679T>A locus was associated with significantly higher doxorubicinol exposure (g.-1679TT vs g.-1679TA, AUC 0-∞ /dose/BSA (hm -5 ): 15.48 (6.18-67.17) vs 8.88 (3.68-21.71), P=0.0001). No significant influence of the three newly identified ABCB5 polymorphisms (c.2T>C, c.343A>G and c.1573G>A) on doxorubicin pharmacokinetics was observed. No polymorphisms were identified in the RLIP76 gene. These findings suggest that ABCC5 polymorphisms may explain partially the interpatient variability in doxorubicin disposition.
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Sutiman et al. (2016) genotyped 100 people of Chinese descent, 100 of Malay descent, and 100 of Indian descent living in Singapore, and among the 300 subjects found no polymorphisms in exons or at exon-intron boundaries.
“By contrast, Sutiman et al. (2016) genotyped 100 people of Chinese descent, 100 of Malay descent, and 100 of Indian descent who were living in Singapore. Among the 300 subjects, the authors found no polymorphisms in exons or at exon-intron boundaries [115].”
From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [115]
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Emran, T. B., Shahriar, A., Mahmud, A. R., Rahman, T., Abir, M. H., Siddiquee, M. F. R., Ahmed, H., Rahman, N., Nainu, F., Wahyudin, E., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.891652 · Cited by 606 · see citing works
Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease?
Hindle, A., Singh, S. P., Pradeepkiran, J. A., Bose, C., Vijayan, M., Kshirsagar, S., Sawant, N. A., & Reddy, P. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116098 · Cited by 14 · see citing works
- Authors
- Lal, S., Sutiman, N., Ooi, L. L., Wong, Z. W., Wong, N. S., Ang, P. C. S., & Chowbay, B.
- Affiliations
- National Cancer Centre Singapore (SG)
- SingHealth (SG)
- National University of Singapore (SG)
- Corresponding author
- Chowbay, B
- Venue
- The Pharmacogenomics Journal
- Published
- 2016-03-15
- Volume
- 17
- Issue
- 4
- Pages
- 337-343
- ISSN
- 1470-269X (ISSN-L)
- 1473-1150
- OpenAlex
- W2300323668
- Cited by
- 26
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 5 · 2017: 1 · 2016: 2
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Pharmacogenomics Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Medical Research Council
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
- Keywords
- ABCB5, ABCC5, RLIP76, breast cancer, genetic polymorphism, doxorubicinol, drug clearance, interpatient variability, Asian patients, ABC transporters
- MeSH terms
- Adult, Aged, Alleles, Antibiotics, Antineoplastic, Breast Neoplasms, Doxorubicin, Exons, Female, Gene Frequency, Genotype, Haplotypes, Humans, Middle Aged, Pharmacogenetics, Polymorphism, Genetic, ATP Binding Cassette Transporter, Subfamily B, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter, Subfamily B, Member 1, GTPase-Activating Proteins, ATP-Binding Cassette, Sub-Family C Proteins, Asian People, Genetic Association Studies
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