title: Correlation of genetic polymorphisms with clinical outcomes in pemetrexed-treated advanced lung adenocarcinoma patients.
abstract: OBJECTIVE
  Pemetrexed is a commonly used chemotherapeutic agent for lung adenocarcinoma patients. We investigated the impact of the genetic polymorphisms on the therapeutic efficacy of pemetrexed in lung adenocarcinoma patients.
  
  
  METHODS
  We performed genotying of 51 polymorphisms of 13 genes in 243 lung adenocarcinoma patients treated with pemetrexed as a single agent for second or more line of therapy.
  
  
  RESULTS
  Total 12 polymorphisms in six genes were showed statistical significances in univariate analysis. After a false-discovery rate correction, the associations between GGH rs16930092 (p = 0.034) and rs10464903 (p = 0.034), and progression-free survival (PFS) were still conserved. Two polymorphisms in ATIC and GGH genes were associated with therapeutic efficacy in multivariate analysis: ATIC rs12995526 for tumor response (p = 0.014) and for overall survival (p = 0.006), and GGH rs16930092 (p = 0.009) for PFS.
  
  
  CONCLUSIONS
  This study shows that polymorphisms on genes related to the metabolic pathway of pemetrexed, especially, ATIC and GGH genes, would have a therapeutic implication in pemetrexed-treated patients with lung adenocarcinoma. Original submitted 10 May 2013; Revision submitted 27 June 2014.
authors.affiliation: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hye In
authors.initials: HI
authors.lastname: Woo
authors.forename: Jung A
authors.initials: JA
authors.lastname: Kim
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Jung
authors.forename: Ka-Kyung
authors.initials: KK
authors.lastname: Kim
authors.forename: Ji Yean
authors.initials: JY
authors.lastname: Lee
authors.forename: Jong-Mu
authors.initials: JM
authors.lastname: Sun
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000235:genetics*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics*; D009367:Neoplasm Staging; D009709:Nucleotide Deaminases / Q000235:genetics*; D000068437:Pemetrexed / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D016896:Treatment Outcome; D011623:gamma-Glutamyl Hydrolase / Q000235:genetics*
chemical_list: D009097:Multienzyme Complexes; C113120:inosine monophosphate synthase; D000068437:Pemetrexed; D019877:Hydroxymethyl and Formyl Transferases; D011623:gamma-Glutamyl Hydrolase; D009709:Nucleotide Deaminases
keywords: ATIC; GGH; NSCLC; SNPs; pharmacogenetics; prognosis