title: Effect of genetic polymorphisms on therapeutic response and clinical outcomes in pancreatic cancer patients treated with gemcitabine.
abstract: OBJECTIVE
  Gemcitabine is the first chemotherapeutic agent to show clinical benefits in pancreatic cancer patients. While interindividual variability in chemoresponse is observed, genetic factors that affect drug metabolism have not been clearly defined. The purpose of this study is to evaluate the relationships between genetic polymorphisms and therapeutic efficacy in pancreatic cancer patients treated with gemcitabine.
  
  
  METHODS
  The study population consisted of 102 pancreatic cancer patients who had been treated with a gemcitabine-based chemotherapeutic regimen. 102 genetic polymorphisms were selected from 23 genes involved in the metabolism and action sites of gemcitabine and screened for polymorphisms using the MassARRAY(®) system. The polymorphisms and haplotypes were analyzed in relation to overall survival (OS), time-to-progression (TTP) and disease progression.
  
  
  RESULTS
  CMPK1 360C>T was significantly associated with OS, TTP and disease progression (p = 0.042, 0.007 and 0.040, respectively, in a dominant genetic model). Additionally, CMPK1 240G>T was correlated with OS and TTP. The frequencies of the haplotypes for the CMPK1, SLC28A1, DCTD and TLE4 genes differed according to disease progression.
  
  
  CONCLUSIONS
  Genetic polymorphisms in genes related to metabolism and action sites of gemcitabine showed associations with the therapeutic efficacy, in terms of OS, TTP and disease progression in pancreatic cancer patients treated with gemcitabine-based chemotherapy. In particular, polymorphisms of the CMPK1 gene seem to provide important prognostic information.
authors: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, Korea.
authors: Hye In
authors: HI
authors: Woo
authors: Ka-Kyung
authors: KK
authors: Kim
authors: Hangseok
authors: H
authors: Choi
authors: Seonwoo
authors: S
authors: Kim
authors: Kee-Taek
authors: KT
authors: Jang
authors: Jun Ho
authors: JH
authors: Yi
authors: Young Suk
authors: YS
authors: Park
authors: Joon Oh
authors: JO
authors: Park
authors: Soo-Youn
authors: SY
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; C019979:cytidylate kinase; D009703:Nucleoside-Phosphate Kinase; D000093542:Gemcitabine