Pharmacogenomic assessment of outcomes of pemetrexed-treated patients with adenocarcinoma of the lung

Minkyu Jung, Chul Ho Lee, Hyung Soon Park, Ji Hyun Lee, youngae kang, Se Kyu Kim, Joon Chang, Dae Joon Kim, SunYoung Rha, Joo Hang Kim, ByoungChul Cho

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8 Citations (Scopus)

Abstract

Purpose: The main objective of this study was to evaluate the association between polymorphisms of the target genes of pemetrexed and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with pemetrexed. Materials and Methods: We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung. Results: Survival was significantly longer with pemetrexed in patients with TS 3RGCC/3RGCC or 3RGGC/3RGGC compared with the other groups (PFS; 5.2 months vs. 3.7 months, p=0.03: OS; 31.8 months vs. 18.5 months, p=0.001). Patients with DHFR 680CC experienced fatigue more frequently (50% vs. 8.6%, p=0.008). Polymorphisms of MTHFR and GARFT were not significantly associated with clinical outcomes of pemetrexed. Conclusion: The TS genotype was associated with survival and one DHFR polymorphism was associated with fatigue in NSCLC patients treated with pemetrexed. Further large prospective studies are required to identify other biomarkers that affect patients being treated with pemetrexed for adenocarcinoma of the lung.

Original languageEnglish
Pages (from-to)854-864
Number of pages11
JournalYonsei medical journal
Volume54
Issue number4
DOIs
Publication statusPublished - 2013 Jul 1

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Pemetrexed
Pharmacogenetics
Outcome Assessment (Health Care)
Thymidylate Synthase
Non-Small Cell Lung Carcinoma
Fatigue
Hydroxymethyl and Formyl Transferases
Genes
Methylenetetrahydrofolate Reductase (NADPH2)
Survival
Adenocarcinoma of lung
Restriction Fragment Length Polymorphisms
Introns
Biomarkers
Genotype
Prospective Studies
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Jung, Minkyu ; Lee, Chul Ho ; Park, Hyung Soon ; Lee, Ji Hyun ; kang, youngae ; Kim, Se Kyu ; Chang, Joon ; Kim, Dae Joon ; Rha, SunYoung ; Kim, Joo Hang ; Cho, ByoungChul. / Pharmacogenomic assessment of outcomes of pemetrexed-treated patients with adenocarcinoma of the lung. In: Yonsei medical journal. 2013 ; Vol. 54, No. 4. pp. 854-864.
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abstract = "Purpose: The main objective of this study was to evaluate the association between polymorphisms of the target genes of pemetrexed and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with pemetrexed. Materials and Methods: We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung. Results: Survival was significantly longer with pemetrexed in patients with TS 3RGCC/3RGCC or 3RGGC/3RGGC compared with the other groups (PFS; 5.2 months vs. 3.7 months, p=0.03: OS; 31.8 months vs. 18.5 months, p=0.001). Patients with DHFR 680CC experienced fatigue more frequently (50{\%} vs. 8.6{\%}, p=0.008). Polymorphisms of MTHFR and GARFT were not significantly associated with clinical outcomes of pemetrexed. Conclusion: The TS genotype was associated with survival and one DHFR polymorphism was associated with fatigue in NSCLC patients treated with pemetrexed. Further large prospective studies are required to identify other biomarkers that affect patients being treated with pemetrexed for adenocarcinoma of the lung.",
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Pharmacogenomic assessment of outcomes of pemetrexed-treated patients with adenocarcinoma of the lung. / Jung, Minkyu; Lee, Chul Ho; Park, Hyung Soon; Lee, Ji Hyun; kang, youngae; Kim, Se Kyu; Chang, Joon; Kim, Dae Joon; Rha, SunYoung; Kim, Joo Hang; Cho, ByoungChul.

In: Yonsei medical journal, Vol. 54, No. 4, 01.07.2013, p. 854-864.

Research output: Contribution to journalArticle

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T1 - Pharmacogenomic assessment of outcomes of pemetrexed-treated patients with adenocarcinoma of the lung

AU - Jung, Minkyu

AU - Lee, Chul Ho

AU - Park, Hyung Soon

AU - Lee, Ji Hyun

AU - kang, youngae

AU - Kim, Se Kyu

AU - Chang, Joon

AU - Kim, Dae Joon

AU - Rha, SunYoung

AU - Kim, Joo Hang

AU - Cho, ByoungChul

PY - 2013/7/1

Y1 - 2013/7/1

N2 - Purpose: The main objective of this study was to evaluate the association between polymorphisms of the target genes of pemetrexed and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with pemetrexed. Materials and Methods: We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung. Results: Survival was significantly longer with pemetrexed in patients with TS 3RGCC/3RGCC or 3RGGC/3RGGC compared with the other groups (PFS; 5.2 months vs. 3.7 months, p=0.03: OS; 31.8 months vs. 18.5 months, p=0.001). Patients with DHFR 680CC experienced fatigue more frequently (50% vs. 8.6%, p=0.008). Polymorphisms of MTHFR and GARFT were not significantly associated with clinical outcomes of pemetrexed. Conclusion: The TS genotype was associated with survival and one DHFR polymorphism was associated with fatigue in NSCLC patients treated with pemetrexed. Further large prospective studies are required to identify other biomarkers that affect patients being treated with pemetrexed for adenocarcinoma of the lung.

AB - Purpose: The main objective of this study was to evaluate the association between polymorphisms of the target genes of pemetrexed and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with pemetrexed. Materials and Methods: We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung. Results: Survival was significantly longer with pemetrexed in patients with TS 3RGCC/3RGCC or 3RGGC/3RGGC compared with the other groups (PFS; 5.2 months vs. 3.7 months, p=0.03: OS; 31.8 months vs. 18.5 months, p=0.001). Patients with DHFR 680CC experienced fatigue more frequently (50% vs. 8.6%, p=0.008). Polymorphisms of MTHFR and GARFT were not significantly associated with clinical outcomes of pemetrexed. Conclusion: The TS genotype was associated with survival and one DHFR polymorphism was associated with fatigue in NSCLC patients treated with pemetrexed. Further large prospective studies are required to identify other biomarkers that affect patients being treated with pemetrexed for adenocarcinoma of the lung.

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