Thymidylate synthase polymorphisms and mRNA expression are independent chemotherapy predictive markers in esophageal adenocarcinoma patients

  • Authors:
    • Hidekazu Kuramochi
    • Koji Tanaka
    • Daniel Oh
    • Bethany J. Lehman
    • Christy M. Dunst
    • Dong Yun Yang
    • Steven R. De Meester
    • Jeffery A. Hagen
    • Kathleen D. Danenberg
    • Tom R. De Meester
    • Peter V. Danenberg
  • View Affiliations

  • Published online on: January 1, 2008     https://doi.org/10.3892/ijo.32.1.201
  • Pages: 201-208
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Abstract

Thymidylate synthase (TS) is known to have polymorphisms in the 5' and 3' untranslated region (UTR). These polymorphisms have been reported to be associated with high TS expression and chemoresistance to 5-FU. The aim of this study was to examine the prognostic roles of the 5'-UTR and 3'-UTR TS polymorphisms in esophageal adenocarcinoma patients, as well as their relation with TS mRNA expression. Eighty-three patients with esophageal adenocarcinoma were assessed. Thirty-four had received 5-FU containing chemotherapy and 49 were treated with surgery alone. Surgically resected tumor tissues were analyzed for TS genotype and TS mRNA expression using a quantitative real-time RT-PCR method. No survival difference was seen between the patients with 3RG allele (3RG group) and non-3RG group among surgery-alone patients. However, among patients with a history of 5-FU-based chemotherapy, the non-3RG group showed significantly better overall survival compared to the 3RG group (p=0.02). Moreover, whereas chemotherapy produced a significant increase in survival for the non-3RG group patients, those in the 3RG group obtained no survival benefit from chemotherapy. When patients were classified by low or high TS mRNA expression levels, low TS expressers obtained survival benefit from chemotherapy while high TS expressers did not, although there was no difference of median TS mRNA levels between 3RG and non-3RG group. The 3'-UTR polymorphism was not associated with overall survival. These results suggest that the status of the TS 5'-UTR polymorphism and TS mRNA expression are independent predictive markers for survival benefit from 5-FU-based therapy.

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January 2008
Volume 32 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kuramochi H, Tanaka K, Oh D, Lehman BJ, Dunst CM, Yang DY, De Meester SR, Hagen JA, Danenberg KD, De Meester TR, De Meester TR, et al: Thymidylate synthase polymorphisms and mRNA expression are independent chemotherapy predictive markers in esophageal adenocarcinoma patients. Int J Oncol 32: 201-208, 2008
APA
Kuramochi, H., Tanaka, K., Oh, D., Lehman, B.J., Dunst, C.M., Yang, D.Y. ... Danenberg, P.V. (2008). Thymidylate synthase polymorphisms and mRNA expression are independent chemotherapy predictive markers in esophageal adenocarcinoma patients. International Journal of Oncology, 32, 201-208. https://doi.org/10.3892/ijo.32.1.201
MLA
Kuramochi, H., Tanaka, K., Oh, D., Lehman, B. J., Dunst, C. M., Yang, D. Y., De Meester, S. R., Hagen, J. A., Danenberg, K. D., De Meester, T. R., Danenberg, P. V."Thymidylate synthase polymorphisms and mRNA expression are independent chemotherapy predictive markers in esophageal adenocarcinoma patients". International Journal of Oncology 32.1 (2008): 201-208.
Chicago
Kuramochi, H., Tanaka, K., Oh, D., Lehman, B. J., Dunst, C. M., Yang, D. Y., De Meester, S. R., Hagen, J. A., Danenberg, K. D., De Meester, T. R., Danenberg, P. V."Thymidylate synthase polymorphisms and mRNA expression are independent chemotherapy predictive markers in esophageal adenocarcinoma patients". International Journal of Oncology 32, no. 1 (2008): 201-208. https://doi.org/10.3892/ijo.32.1.201