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.

Journal Article (Journal Article)

PURPOSE: 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 AND MATERIALS: 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.

Full Text

Duke Authors

Cited Authors

  • Liao, Z; Liu, H; Swisher, SG; Wang, L; Wu, T-T; Correa, AM; Roth, JA; Cox, JD; Komaki, R; Ajani, JA; Wei, Q

Published Date

  • March 1, 2006

Published In

Volume / Issue

  • 64 / 3

Start / End Page

  • 700 - 708

PubMed ID

  • 16242255

International Standard Serial Number (ISSN)

  • 0360-3016

Digital Object Identifier (DOI)

  • 10.1016/j.ijrobp.2005.08.008


  • eng

Conference Location

  • United States