Correlation Between Thymidylate Synthase Gene Polymorphism And Clinical Outcome Of Postoperative Adjuvant Chemotherapy In Rectal Cancer Patients

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 mononuclear 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(χ2=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).Conclusion:TS 5’-UTR tandem repeat polymorphisms had potential utilization for personalized therapy in Chinese population.