Implication of TYMP genetic variation on the prognosis of patients with colorectal cancer who received capecitabine-based adjuvant chemotherapy after surgical resection: a real-world exploratory study

Abstract Background Thymidine Phosphorylase (TYMP) gene was of crucial significance in the process of colorectal cancer (CRC) development and also played an important role in capecitabine metabolism. Present study was to identify the association between TYMP polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy. Methods A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients with CRC were collected for the genotyping of TYMP polymorphism and TYMP mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate were adjusted by Cox regression analysis. Expression of TYMP according to genotype status was analyzed using non-parameter test. Results The median disease-free survival (DFS) of the 218 patients with CRC was 4.6 years, and the median overall survival (OS) was 5.8 years. Regarding the polymorphism analysis, only rs11479 was of clinical significance. The prevalence of rs11479 in TYMP among the 218 patients indicated that minor allele frequency was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which accorded with Hardy-Weinberg Equilibrium (P=0.825). Prognostic analysis according to rs11479 genotype status suggested that the median DFS of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (P=0.004). Furthermore, the median OS of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (P=0.033). In order to adjust the confounding factors which might contribute to OS, a multivariate Cox regression analysis was introduced and the results exhibited that rs11479 polymorphism was an independent factor for DFS (HR=1.64, P=0.009). Additionally, of the 65 PBMC specimens, the mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of TYMY than that of patients with GG genotype (P<0.001). Conclusions TYMP gene polymorphism rs11479 might involve in the prognosis of patients with CRC who received capecitabine based adjuvant chemotherapy through mediation of the mRNA expression of TYMP. Conclusion of present study should be confirmed in prospective clinical trial subsequently.