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Pharmacogenomic Assessment of Outcomes of Pemetrexed-Treated Patients with Adenocarcinoma of the Lung

 Minkyu Jung  ;  Chul Ho Lee  ;  Hyung Soon Park  ;  Ji Hyun Lee  ;  Young Ae Kang  ;  Se Kyu Kim  ;  Joon Chang  ;  Dae Joon Kim  ;  Sun Young Rha  ;  Joo Hang Kim  ;  Byoung Chul Cho 
 YONSEI MEDICAL JOURNAL, Vol.54(4) : 854-864, 2013 
Journal Title
Issue Date
Adenocarcinoma/drug therapy* ; Adenocarcinoma/genetics* ; Adenocarcinoma/mortality ; Adult ; Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic/pharmacology ; Antimetabolites, Antineoplastic/therapeutic use* ; Antimetabolites, Antineoplastic/toxicity ; Female ; Glutamates/pharmacology ; Glutamates/therapeutic use* ; Glutamates/toxicity ; Guanine/analogs & derivatives* ; Guanine/pharmacology ; Guanine/therapeutic use ; Guanine/toxicity ; Humans ; Lung Neoplasms/drug therapy* ; Lung Neoplasms/genetics* ; Lung Neoplasms/mortality ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Middle Aged ; Pemetrexed ; Pharmacogenetics ; Phosphoribosylglycinamide Formyltransferase/genetics ; Polymorphism, Single Nucleotide* ; Tetrahydrofolate Dehydrogenase/genetics ; Thymidylate Synthase/genetics
Polymorphism ; lung neoplasms ; pemetrexed
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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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Young Ae(강영애) ORCID logo https://orcid.org/0000-0002-7783-5271
Kim, Dae Joon(김대준)
Kim, Se Kyu(김세규)
Kim, Joo Hang(김주항)
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Park, Hyung Soon(박형순)
Lee, Ji Hyun(이지현)
Lee, Chul Ho(이철호)
Chang, Joon(장준) ORCID logo https://orcid.org/0000-0003-4542-6841
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
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