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

 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 
 PHARMACOGENETICS AND GENOMICS, Vol.26(3) : 116-125, 2016 
Journal Title
Issue Date
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
non-small-cell lung cancer ; paclitaxel ; polymorphism ; SLCO1B3 ; survival ; toxicity
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Hang(김주항)
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Park, Hyung Soon(박형순)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Cho, Arthur Eung Hyuck(조응혁) ORCID logo https://orcid.org/0000-0001-8670-2473
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