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Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphism in normal tissue as predictors of
Anders Jakobsen1, Jens Nederby Nielsen, Niels Gyldenkerne
1Danish Colorectal Cancer, Group South, Vejle Hospital, 7100 Vejle, Denmark. aja@vs.vejleamt.dk
Purpose:
To analyze thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU) sensitivity.
Patients And Methods:
The study included a retrospective analysis of 88 patients with metastatic colorectal cancer and a prospective trial with 51 patients also with measurable metastases. All patients were treated with FU and leucovorin. The analysis of gene polymorphism was performed on normal intestinal tissue and lymphocytes.
Results:
The response rate was significantly higher in patients with TS 3R/3R or MTHFR 677 TT gene polymorphism compared with the other groups. The difference of response rate translated to a difference in time to progression. Similar results were observed in the retrospective analysis and the prospective confirmatory trial.
Conclusion:
The analysis of gene polymorphism allows delineation of a group of patients (30%) with a response rate to a single drug of approximately 50%. This information should be used in the design of tailored treatment.
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Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
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