Influence of TYMP Polymorphism on Clinical Outcomes of Colorectal Cancer Patients Received Adjuvant Chemotherapy After R0 Resection

Abstract

Objective To investigate the association between thymidine phosphorylase(TYMP) polymorphism and clinical outcomes of colorectal cancer(CRC) patients received adjuvant chemotherapy after R0 resection. Methods We included 198 patients with colorectal cancer who underwent adjuvant chemotherapy. Peripheral blood and the postoperative tissue specimen of the CRC patients were collected for the genotyping of 5633C > T and TYMP mRNA expression, respectively. The relationship between 5633C > T genotype and other variables was analyzed by different analysis methods. Additionally, the mRNA expression of TYMP according to 5633C > T were analyzed by real-time PCR. Results The prevalence of 5633C > T in TYMP among the CRC patients were as follows: 126(63.64%) cases of CC genotype, 61(30.81%) cases of CT genotype, 11(5.55%) cases of TT genotype, minimum allele frequency of 5633C > T was 0.21. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.323). There were no statistical differences in the distribution of the genotypes in baseline data. CT genotype and TT genotype patients were merged in the comparison of prognosis. The OS of patients with wild-type CC genotype was significantly lower than those with CT and TT genotypes (P=0.009). Adjusted in multivariate Cox regression analysis, CC genotype was an independent factor for OS (P=0.015). Additionally, of the 87 postoperative tissue specimens, the expression of TYMP mRNA in cancer tissues of the patients with CT or TT genotypes were significantly higher than those with wild-type CC genotype (P=0.019). Conclusion TYMP gene polymorphism 5633C > T may influence the prognosis of CRC patients who received capecitabine-based adjuvant chemotherapy by affecting the mRNA expression of TYMP.

Keywords

• colorectal cancer
• thymidine phosphorylase
• capecitabine
• polymorphism