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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)116-125
Number of pages10
JournalPharmacogenetics and Genomics
Volume26
Issue number3
DOIs
Publication statusPublished - 2016 Jan 1

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Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Genotype
Oocytes
Drug Therapy
Genetic Polymorphisms
Disease-Free Survival
Anemia
Survival
Glycolysis
Pharmaceutical Preparations
Pharmacokinetics
Pharmacogenomic Testing
Incidence
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Park, Hyung Soon ; Lim, Sun Min ; Shin, Ho Jung ; Cho, Arthur ; Shin, Jae Gook ; Lee, Min Goo ; Kim, Hye Ryun ; Kim, Joo Hang ; Cho, Byoung Chul. / Pharmacogenetic analysis of advanced non-small-cell lung cancer patients treated with first-line paclitaxel and carboplatin chemotherapy. In: Pharmacogenetics and Genomics. 2016 ; Vol. 26, No. 3. pp. 116-125.
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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.",
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Pharmacogenetic analysis of advanced non-small-cell lung cancer patients treated with first-line paclitaxel and carboplatin chemotherapy. / Park, Hyung Soon; Lim, Sun Min; Shin, Ho Jung; Cho, Arthur; Shin, Jae Gook; Lee, Min Goo; Kim, Hye Ryun; Kim, Joo Hang; Cho, Byoung Chul.

In: Pharmacogenetics and Genomics, Vol. 26, No. 3, 01.01.2016, p. 116-125.

Research output: Contribution to journalArticle

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T1 - Pharmacogenetic analysis of advanced non-small-cell lung cancer patients treated with first-line paclitaxel and carboplatin chemotherapy

AU - Park, Hyung Soon

AU - Lim, Sun Min

AU - Shin, Ho Jung

AU - Cho, Arthur

AU - Shin, Jae Gook

AU - Lee, Min Goo

AU - Kim, Hye Ryun

AU - Kim, Joo Hang

AU - Cho, Byoung Chul

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N2 - 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.

AB - 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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