P-0001 - Association of THYMIDYLATE synthase gene polymorphisms and the outcome of adjuvant therapy in gastric cancer

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Anti-Cancer Agents & Biologic Therapy
Gastric Cancer
Translational Research
Presenter Anastasia Udilova
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors A. Udilova, M. Nemtsova, T. Kchorobryh
  • First Moscow Medical University, Moscow/RU



Thymidylate synthase (TS) is a key enzyme in nucleotide biosynthesis and is the main intracellular target of 5-FU. There are TYMS polymorphisms in the 5′ and 3′ untranslated region associated with expression of TS.


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 58 gastric cancer patients after surgical treatment and treated with 5-fluorouracil and oxaliplatin-based adjuvant chemotherapy.


In the study of the effectiveness of chemotherapy 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 adjuvant chemotherapy (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 adjuvant chemotherapy. 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. Evaluating the relationship between the survival and TS genotypes, it was observed that 3R homozygous patients showed significantly shorter DFS (p= 0.049) and OS (p = 0.046) than other 5`TSUTR polymorphisms. At the same time, neither the 3`TSUTR genotypes, nor 5`TSUTR + SNT genotypes were significantly associated with DFS and OS.


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.