The Investigation Of Relationship Between The Polymorphism Of Thymidylate Synthetase Gene And Therapeutic Effect Of Gastric Cancer To Fluorouracil-based Chemotherapy

Background:Gastric cancer is one of the most common malignant tumor in our country.Because of onset delitescence,the diagnose in early stage is difficult,most patients present advanced stage when definite diagnosis be made.Moreover,there is high recurrent rate after radical therapy.So chemotherapy is one of the most important methods.5-fluorouracil(5-Fu) is the basic and common medicine for gastric cancer. There is a great difference of the therapeutic effect among the gastric cancer patients who were treated by 5-fluorouracil-based chemotherapy regimens.The difference of the therapeutic effect was caused by many factors,such as the biologic characteristic of gastric cancer,the sensitivity to medicine of individual,and so on.In these factors,the most one is the function and expression change of thymidylate synthetase which was mainly caused by thymidylate synthetase gene polymorphism.Thus,the investigating the relationship between polymorphism of thymidylate synthetase gene and therapeutic effect of gastric cancer to 5-fluorouracil-based chemotherapy may have important significance on tailoring medication and improving chemotherapy effect.Objective:To investigate the relationship between polymorphism in the 5'-untranslated region(5'-UTR) and 3'-untranslated region(3'-UTR) of thymidylate synthetase gene and therapeutic effect of gastric cancer to 5-fluorouracil-based chemotherapy.TS gene promoter have either double or triple tandem repeats of a 28-bp sequence in 5'-UTR and a 6bp variation at bp1494 in 3'-UTR.It may have important significance on tailoring medication and improving chemotherapy effect. All patients were treated with 5-Fu-based chemotherapeutic regimens and DNA of peripheral blood leukocytes was obtained before chemotherapy.TS 5'-UTR and 3'-UTR genotypes were detected by PCR-DHPLC method.Results:(1)Of all the 74 cases,the proportion of 3R/3R genotype and 2R/2R,2R/3R genotypes were 21.6%(16/74) and 78.4%(58/74).The response rates to chemotherapy were 6.3%(1/16) and 36.2%(21/58).The latter was significantly higher than the former(χ~2=4.05 p＜0.05).(2)Of all the 74 cases,the proportion of TS 5'-UTR +/+6bp,+/-6bp and -/-6bp were 5.4%(4/74),52.7%(39/74) and 41.9%(31/74).The response rates to chemotherapy were 0%(0/4),23.1%(9/39) and 41.9%(13/31).There was no significant difference in these groups(P=0.076).Conclusion:The study suggested that the polymorphism of TS 5'-UTR was associated with therapeutic effect of gastric cancer to 5-Fu.However,there was no relationship between the polymorphism of TS 3'-UTR and the therapeutic effect of 5-Fu.It was suggested that detection of TS 5'-UTR genotype may make for guiding the chemotherapy of the advanced SC.