title: Polymorphism at the 3'-UTR of the thymidylate synthase gene: a potential predictor for outcomes in Caucasian patients with esophageal adenocarcinoma treated with preoperative chemoradiation.
abstract: OBJECTIVE
  To test the hypothesis that TS3'UTR polymorphisms predict outcomes in 146 Caucasian patients with esophageal adenocarcinoma treated with preoperative 5-fluorouracil-based chemoradiation.
  
  
  METHODS
  DNA was extracted from hematoxylin-and-eosin stained histologic slides of normal esophageal or gastric mucosa sections from paraffin blocks of esophagectomy specimens. Genotypes of the TS3'UTR polymorphism were determined by polymerase chain reaction for a 6-bp insertion. The genotype groups (0bp/0bp, 6bp/0bp, and 6bp/6bp) were compared for clinical features and overall survival, recurrence-free-survival, locoregional control (LRC), and distant metastasis control. Multivariable Cox regression analyses were performed to find independent predictors for the stated outcomes.
  
  
  RESULTS
  There was a trend of association between 6bp/6bp genotype and a decreased risk of local regional recurrence (hazards ratio = 0.211, 95% confidence interval = 0.041-1.095, p = 0.06) compared with other genotypes. There was a trend that patients with 6bp/6bp genotype had a higher 3-year probability of LRC compared with patients with the other two genotypes combined (p = 0.07); however, the difference was not statistically significant.
  
  
  CONCLUSIONS
  The null hypotheses were not rejected in this study, probably owing to small sample size or the single gene examined. Prospective studies with adequate statistical power analyzing a family of genes involved in the 5-fluorouracil metabolism are needed to assess genetic determinants of treatment-related outcomes in esophageal adenocarcinoma.
authors.affiliation: Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. zliao@mdanderson.org
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.forename: Hongji
authors.initials: H
authors.lastname: Liu
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swisher
authors.forename: Luo
authors.initials: L
authors.lastname: Wang
authors.forename: Tsung-Teh
authors.initials: TT
authors.lastname: Wu
authors.forename: Arlene M
authors.initials: AM
authors.lastname: Correa
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000230:Adenocarcinoma / Q000201:enzymology* / Q000208:ethnology / Q000401:mortality; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000208:ethnology / Q000401:mortality; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012044:Regression Analysis; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000235:genetics*; D044465:White People
chemical_list: D020413:3' Untranslated Regions; D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil