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Pharmacogenetic analysis of advanced non-small-cell lung cancer patients treated with first-line paclitaxel and carboplatin chemotherapy

Authors
 Hyung Soon Park  ;  Sun Min Lim  ;  Ho Jung Shin  ;  Arthur Cho  ;  Jae-Gook Shin  ;  Min Goo Lee  ;  Hye Ryun Kim  ;  Joo Hang Kim  ;  Byoung Chul Cho 
Citation
 Pharmacogenetics and Genomics, Vol.26(3) : 116-125, 2016 
Journal Title
 Pharmacogenetics and Genomics 
ISSN
 1744-6872 
Issue Date
2016
MeSH
ATP Binding Cassette Transporter, Sub-Family B/genetics ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; Carboplatin/administration & dosage* ; Carboplatin/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/mortality ; Female ; Glycolysis/drug effects ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Lung Neoplasms/drug therapy* ; Lung Neoplasms/genetics ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Organic Anion Transporters, Sodium-Independent/genetics* ; Paclitaxel/administration & dosage* ; Paclitaxel/therapeutic use Polymorphism, Single Nucleotide ; Prognosis ; Prospective Studies ; Solute Carrier Organic Anion Transporter Family Member 1B3 ; Survival Analysis
Keywords
non-small-cell lung cancer ; paclitaxel ; polymorphism ; SLCO1B3 ; survival ; toxicity
Abstract
BACKGROUND: Genetic polymorphisms contribute toward interindividual variations in drug response. We investigated the effects of genetic polymorphisms on the clinical outcome of advanced non-small-cell lung cancer patients with first-line paclitaxel and carboplatin. MATERIALS AND METHODS: A total of 194 non-small-cell lung cancer patients were prospectively enrolled from January 2010 to January 2013. We genotyped 11 polymorphisms in seven genes involved in the glycolysis pathway and the related pharmacokinetic/pharmacodynamic pathway. Genetic associations with PET-SUV, survival outcome, and toxicity were analyzed, and in-vitro drug transport activity was measured in the oocyte system. RESULTS: Patients with the c.334 T>G and c.699 G>A homozygous variant in SLCO1B3 showed a higher incidence of grade 3/4 anemia (P=0.002). Transport activities of oocyte that overexpress the SLCO1B3 c.699 G>A variant showed a significantly decreased uptake of paclitaxel compared with the wild-type expressing oocytes. In addition, patients with GG/GA/AA genotypes of ABCB1, c.2677 T>G/A locus showed inferior progression-free survival (hazard ratio=1.49, P=0.017) compared with other genotypes. The GA genotype of HIF1A, c.1834 G>A locus was associated with inferior progression-free survival compared with the GG genotype (hazard ratio=2.47, P=0.008). CONCLUSION: This study showed that the SLCO1B3 c.699 G>A polymorphism may predict anemia and ABCB1, HIF1A polymorphism are highly predictive for worse survival in advanced NSCLC with first-line paclitaxel and carboplatin.
Full Text
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=01213011-201603000-00002&LSLINK=80&D=ovft
DOI
10.1097/FPC.0000000000000196
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실)
Yonsei Authors
김주항(Kim, Joo Hang)
김혜련(Kim, Hye Ryun) ORCID logo https://orcid.org/0000-0002-1842-9070
박형순(Park, Hyung Soon)
이민구(Lee, Min Goo) ORCID logo https://orcid.org/0000-0001-7436-012X
조병철(Cho, Byoung Chul) ORCID logo https://orcid.org/0000-0002-5562-270X
조응혁(Cho, Arthur Eung Hyuck) ORCID logo https://orcid.org/0000-0001-8670-2473
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146322
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