Thymidylate synthase gene polymorphism predicts disease free survival in stage II-III rectal adenocarcinoma patients receiving adjuvant 5-FU-based chemotherapy

Background: The objective is to investigate whether thymidylate synthase gene TS 5'-UTR polymorphism of peripheral blood mononuclear cells are associated with clinical outcomes of patients with stage II-III rectal adenocarcinoma treated with adjuvant 5-fluorouracil (5-FU) chemotherapy in Chinese population. Methods: One hundred and seventeen pathologically diagnosed colorectal adenocarcinoma patients with stage II-III, who underwent curative resection and received 5-fluoropyrimidine-based adjuvant chemotherapy were enrolled to this study. The 5'-TSER polymorphisms determined from the peripheral blood mononudear cells were measured by Direct Sequencing. Kaplan-Meier curves and log-rank tests were used for survival analysis. The independent prognostic factors influencing DFS and OS were estimated by Cox proportional hazards model. Results: The distribution of TS 5'-UTR polymorphisms ware 2.6% 2R/2R, 31.6% 2R/3R and 65.8% 3R/3R respectively, which was fitted with Hard-Weinberg equilibrium (chi(2)=0.345, P=0.558). Stage, N stage, number of mesenteric lymph node metastasis, KPS, and 5*-UTR polymorphisms (2R/2R/2R/3R vs. 3R/3R, P<0.001) were significantly associated with DFS. Meanwhile, gender (female vs. male, P=0.025) and adjuvant radiotherapy (yes vs. no, P=0.025) were significantly associated with OS. Multivariate Cox regression showed that KPS score (HR =0.947, P=0.007), TS 5'-UTR polymorphism (HR =0.455, P=0.004) were independent prognostic factors for DFS. Whereas, KPS score was the only independent prognostic factors for OS (HR =0.910, P=0.005). Conclusions: TS 5'-UTR tandem repeat polymorphisms had potential utilization for personalized therapy in Chinese population.