The influence of thymidylate synthase polymorphisms on the prognosis of gastric cancer patients treated with 5-FU-based adjuvant chemotherapy / 肿瘤

ABSTRACT

Objective: To investigate the effects of the tandem repeat polymorphisms in the enhancer region (ER) of thymidylate synthase (TS) gene and the 6-bp deletion/insertion (del6/ins6) polymorphism in the 3′ untranslated region (3′-UTR) of TS gene on the clinical outcomes of gastric cancer patients treated with 5-FU-based adjuvant chemotherapy. Methods: One hundred and sixteen patients with gastric cancer were treated with 5-FU-based adjuvant chemotherapy. The polymorphisms of TSER and TS 3′ -UTR in those patients were determined by polymerase chain reaction (PCR) method. Results: Of the 116 patients, the frequencies of the TSER 2R/2R, 2R/3R and 3R/3R were 7.8% (9/116), 31.9% (37/116), and 60.3% (70/116), respectively; the frequencies of the TS3′-UTR ins6/ins6, ins6/del6 and del6/del6 were 9.5% (11/116), 41.4% (48/116) and 49.1% (57/116), respectively. The median survival period in ins6/ins6 carriers was significantly shorter than that of del6/del6 (P = 0.017) or ins6/del6 (P = 0.022) carriers. There was no significant difference in median relapse-free survival period between different TSER carriers (P > 0.05). COX multivariate analysis showed that the ins6/ins6 carriers had increased death risk (P <0.05) compared to the other two genotypes. The median no-recurrence survival period had no statistical difference between them. Conclusion: The polymorphism of TS 3 UTR ins6/del6 may be an independent factor for the prognosis of gastric cancer patients treated with 5-FU-based adjuvant chemotherapy.