Abstract
Aim: Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy.Patients and Methods: 251 patients diagnosed with stage III colon carcinoma treated with surgery followed by 5-FU based adjuvant therapy were selected. The variable number of tandem repeats (VNTR) and the single nucleotide polymorphism (SNP) in the 5′-untranslated region of the TS gene were genotyped.Results: There was a positive association between tumor T stage and the VNTR genotypes (p=0.05). In both univariate and multivariate survival analysis no effects of the studied polymorphisms on survival were found. However, there was an association between both polymorphisms and age. Among patients younger than 60 years, the patients homozygous for 2R seemed to have a better overall survival, whereas among the patients older than 67 this longer survival was seen by the carriers of other genotypes.Conclusion: We conclude that the TS VNTR and SNP do not predict response to 5-FU therapy in patients with stage III colon carcinoma. However, age appears to modify the effects of TS polymorphisms on survival.
Highlights
251 patients diagnosed with stage III colon carcinoma treated with surgery followed by 5-FU based adjuvant therapy were selected
We conclude that the thymidylate synthase (TS) variable number of tandem repeats (VNTR) and single nucleotide polymorphism (SNP) do not predict response to 5-FU therapy in patients with stage III colon carcinoma
We have recently reported the reliability of different methods for TS typing, like genotyping of three known gene polymorphisms, TS protein expression quantitation, TS gene amplification and loss of heterozygosity in predicting 5-FU therapy response [12]
Summary
The predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. We aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy. The aim of this study was to determine the value of the TS gene 5 -UTR polymorphisms as a possible molecular marker for 5-FU response in a well defined, homogeneous population of stage III colon cancer patients who had been treated with 5-FU based adjuvant chemotherapy. This study aimed to elucidate the value of TS gene polymorphisms as possible molecular marker of therapy response in stage III colon carcinoma patients treated with adjuvant 5-FU chemotherapy
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