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

Zhongxing Liao, Hongji Liu, Stephen G. Swisher, Luo Wang, Tsung Teh Wu, Arlene M. Correa, Jack A. Roth, James D. Cox, Ritsuko Komaki, Jaffer A. Ajani, Qingyi Wei

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)700-708
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume64
Issue number3
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Fingerprint

Thymidylate Synthase
polymorphism
3' Untranslated Regions
genes
Adenocarcinoma
Genotype
predictions
null hypothesis
Genes
trends
polymerase chain reaction
metastasis
paraffins
metabolism
chutes
determinants
Fluorouracil
hazards
regression analysis
insertion

Keywords

  • Biomarker
  • Concurrent chemoradiation
  • Esophageal adenocarcinoma
  • Esophagectomy
  • TS3-UTR polymorphism

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

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. / Liao, Zhongxing; Liu, Hongji; Swisher, Stephen G.; Wang, Luo; Wu, Tsung Teh; Correa, Arlene M.; Roth, Jack A.; Cox, James D.; Komaki, Ritsuko; Ajani, Jaffer A.; Wei, Qingyi.

In: International Journal of Radiation Oncology Biology Physics, Vol. 64, No. 3, 01.03.2006, p. 700-708.

Research output: Contribution to journalArticle

Liao, Zhongxing ; Liu, Hongji ; Swisher, Stephen G. ; Wang, Luo ; Wu, Tsung Teh ; Correa, Arlene M. ; Roth, Jack A. ; Cox, James D. ; Komaki, Ritsuko ; Ajani, Jaffer A. ; Wei, Qingyi. / 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. In: International Journal of Radiation Oncology Biology Physics. 2006 ; Vol. 64, No. 3. pp. 700-708.
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abstract = "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.",
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T1 - Polymorphism at the 3′-UTR of the thymidylate synthase gene

T2 - A potential predictor for outcomes in Caucasian patients with esophageal adenocarcinoma treated with preoperative chemoradiation

AU - Liao, Zhongxing

AU - Liu, Hongji

AU - Swisher, Stephen G.

AU - Wang, Luo

AU - Wu, Tsung Teh

AU - Correa, Arlene M.

AU - Roth, Jack A.

AU - Cox, James D.

AU - Komaki, Ritsuko

AU - Ajani, Jaffer A.

AU - Wei, Qingyi

PY - 2006/3/1

Y1 - 2006/3/1

N2 - 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.

AB - 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.

KW - Biomarker

KW - Concurrent chemoradiation

KW - Esophageal adenocarcinoma

KW - Esophagectomy

KW - TS3-UTR polymorphism

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