The influence of Thymidine Phosphorylase genetic variation on clinical outcomes and safety of colorectal cancer patients received adjuvant chemotherapy after R0 resection

Abstract

Objective: To study the association between Thymidine Phosphorylase (TYMP) genetic variation and clinical outcomes and safety of postoperative colorectal cancer (CRC) patients. Methods: A total of 235 patients with colorectal cancer underwent surgical treatment were included in this retrospective analysis. Peripheral blood and the postoperative tissue specimen of the CRC patients were collected for the genotyping of polymorphism and TYMP mRNA expression, respectively. The correlation between polymorphism and clinical outcomes and safety of postoperative CRC patients were analysed. Results: Located in the upstream, 5633C>T was of clinical significance. The prevalence of 5633C>T in TYMP among the CRC patients were as follows: CC genotype 149 cases (63.40%), CT genotype 73 cases (31.06%), TT genotype 13 cases (5.54%), minor allele frequency of 5633C>T is 0.21. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.313). CT genotype and TT genotype patients were merged in the comparison of prognosis. The survival analysis of patients with different genotypes found that the median Overall Survival (OS) of CT/TT genotype and CC genotype were 5.8 and 4.5 year, which was statistically significant (P=0.009). Adjusted in multivariate Cox regression analysis, CT/TT genotype was an independent favorable factor for OS (HR=0.67, P=0.015). Additionally, of the 87 postoperative tissue specimens, the results showed that the expression of TYMP in cancer tissues of the patients with CT or TT genotypes were significantly higher than those of the wild type CC genotype patients (P=0.019). And the safety analysis showed that the incidence of grade 3 hand-foot syndrome among CT/TT genotype patients were higher than that of CC genotype patients (33.72% vs 20.13%, OR=1.68, P=0.021). Conclusion: The polymorphism 5633C>T of TYMP may impact the prognosis of CRC patients received adjuvant chemotherapy by influencing the mRNA expression of TYMP.