TYMS GENE POLYMORPHISMS IN PATIENTS WITH GASTRIC CANCER, THE RELATIONSHIP WITH LONG-TERM RESULTS OF COMBINED TREATMENT

M.V. Nemtsova1, 2, A.A. Udilova1, D.V. Zaletaev1, T.V. Khorobrych1
1I. M. Sechenov First Moscow State Medical University, Trubetskaya Str., 8, Moscow, Russian Federation, 119991;
2Russian Medical Academy of Postgraduate Education, Barrikadnaya Str., 2/1, Moscow, Russian Federation, 123995

Introduction. Thymidylate synthase (TS) is a key enzyme in nucleotide biosynthesis and is the main intracellular target of 5-FU. We investigated the clinical and prognostic importance of TYMS gene 5' (TSR2/TSR3 and G>C) and 3' (del 6) untranslated region polymorphisms for gastric cancer patients. The aim of the study. We investigated the clinical and prognostic importance of TYMS polymorphisms for gastric cancer patients. We examined of 5' (TSR2/TSR3 and G>C) and 3' (del 6) untranslated region polymorphisms in 80 gastric cancer patients after surgical treatment and chemotherapy with 5-fluorouracil. Methods. PCR-RFLP. Results. We have shown, that the genotype 2R/2R is significantly more often found in patients with regional lymph node metastases (N1- 3) (p=0,0475), genotype -6/-6 is significantly more common in patients with intestinal gastric cancer (p=0,0375), as well as in patients, who have high/moderately differentiated adenocarcinoma (p=0,033).In the study of the effectiveness of chemotherapy in 58 gastric cancer patients, we have shown, that genotype 3G/3G was associated with the poor prognosis, development of local recurrence, carcinomatosis, the appearance of distant metastases during the first 3 years after surgery and 5-FU treatment (p=0,024). Genotype 2G/3C was significantly frequent (p=0,023) in patients without progression of the disease within the first 3 years after surgery and 5-FU treatment. In the study of the TYMS gene 3'-untranslated region (del 6) polymorphism in the patients after surgical treatment and chemotherapy, we found no significant differences. Conclusion. We suggest that TYMS 5'UTR and 3'UTR polymorphisms can serve as individual prognostic factors and as predictors of adjuvant treatment effectiveness in patients with locally advanced gastric cancer.
Keywords: 
thymidylate synthase, TYMS gene, polymorphisms, genotype, 5-FU chemotherapy