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

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.

journal_name

Int J Oncol

journal_title

International journal of oncology

authors

Kuramochi H,Tanaka K,Oh D,Lehman BJ,Dunst CM,Yang DY,De Meester SR,Hagen JA,Danenberg KD,De Meester TR,Danenberg PV

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

201-8

issue

1

eissn

1019-6439

issn

1791-2423

journal_volume

32

pub_type

杂志文章

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