Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0134102
Title: Association of ABCB1 and FLT3 polymorphisms with toxicities and survival in asian patients receiving sunitinib for renal cell carcinoma
Authors: Chu Y.-H.
Li H. 
Tan H.S.
Koh V.
Lai J.
Phyo W.M.
Choudhury Y.
Kanesvaran R. 
Chau N.M.
Toh C.K.
Ng Q.S.
Tan P.H.
Chowbay B. 
Tan M.-H. 
Keywords: BIM protein
breast cancer resistance protein
CD135 antigen
multidrug resistance protein 1
sunitinib
tumor marker
vasculotropin receptor 2
ABCB1 protein, human
antineoplastic agent
CD135 antigen
FLT3 protein, human
indole derivative
multidrug resistance protein
pyrrole derivative
sunitinib
ABCB1 gene
ABCG2 gene
adult
allele
Article
Asian
BIM gene
cancer survival
Caucasian
comorbidity
controlled study
drug safety
ethnicity
female
FLT3 gene
gene frequency
genetic association
genetic marker
genetic polymorphism
hand foot syndrome
haplotype
human
kidney carcinoma
leukopenia
liver toxicity
major clinical study
male
multiple cycle treatment
neutropenia
prediction
progression free survival
thrombocytopenia
validation process
VEGFR2 gene
adolescent
adverse drug reaction
aged
Asian continental ancestry group
Carcinoma, Renal Cell
disease free survival
ethnology
genetic predisposition
genetics
genotype
Kidney Neoplasms
metastasis
middle aged
Singapore
single nucleotide polymorphism
treatment outcome
young adult
Adolescent
Adult
Aged
Antineoplastic Agents
Asian Continental Ancestry Group
Carcinoma, Renal Cell
Disease-Free Survival
Drug-Related Side Effects and Adverse Reactions
Female
fms-Like Tyrosine Kinase 3
Gene Frequency
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Indoles
Kidney Neoplasms
Male
Middle Aged
Neoplasm Metastasis
P-Glycoproteins
Polymorphism, Single Nucleotide
Pyrroles
Singapore
Treatment Outcome
Young Adult
Issue Date: 2015
Citation: Chu Y.-H., Li H., Tan H.S., Koh V., Lai J., Phyo W.M., Choudhury Y., Kanesvaran R., Chau N.M., Toh C.K., Ng Q.S., Tan P.H., Chowbay B., Tan M.-H. (2015). Association of ABCB1 and FLT3 polymorphisms with toxicities and survival in asian patients receiving sunitinib for renal cell carcinoma. PLoS ONE 10 (8) : e0134102. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0134102
Rights: Attribution 4.0 International
Abstract: Sunitinib is a tyrosine kinase inhibitor used as first-line treatment for metastatic renal cell carcinoma (mRCC). Asian ethnicity has been previously associated with lower clearance and greater toxicities for sunitinib treatment, relative to Caucasian ethnicity. Research focusing on identifying corresponding biomarkers of efficacy and toxicity has been hitherto conducted in Caucasian populations, and few of the reported associations have been externally validated. Our work thus aims to investigate candidate biomarkers in Asian patients receiving sunitinib, comparing the observed genotype effects with those reported in Caucasian populations. Using data from 97 Asian mRCC patients treated with sunitinib, we correlated 7 polymorphisms in FLT3, ABCB1, VEGFR2, ABCG2 and BIMwith patient toxicities, response, and survival. We observed a stronger association of FLT3 738T genotype with leucopenia in our Asian dataset than that previously reported in Caucasian mRCC patients (odds ratio [OR] =8.0; P=0.03). We observed significant associations of FLT3 738T (OR=2.7), ABCB11236T (OR=0.3), ABCB1 3435T (OR=0.1), ABCB1 2677T (OR=0.4), ABCG2 421A (OR=0.3) alleles and ABCB1 3435, 1236, 2677 TTT haplotype (OR=0.1) on neutropenia. Primary resistance (OR=0.1, P=0.004) and inferior survival (progression-free: hazard ratio [HR]=5.5, P=0.001; overall: HR=5.0, P=0.005) were associated with the ABCB1 3435, 1236, 2677 TTT haplotype. In conclusion, ABCB1 and FLT3 polymorphisms may be helpful in predicting sunitinib toxicities, response and survival benefit in Asian mRCC patients. We have also validated the association between FLT3 738T and sunitinib-induced leucopenia previously reported in Caucasian populations, but have not validated other reported genetic associations. © 2015 Chu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161494
ISSN: 19326203
DOI: 10.1371/journal.pone.0134102
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pone_0134102.pdf346.95 kBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

19
checked on Nov 18, 2020

Page view(s)

101
checked on Nov 20, 2020

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons