Effect of thymidylate synthase gene polymorphism on the response to chemotherapy and clinical outcome of non-small cell lung cancer patients

Abstract

Genetic polymorphisms of thymidylate synthase (TYMS) gene have been reported to be associated with development or prognosis of several cancers. However, the association between polymorphisms of TYMS gene and clinical outcomes of non-small cell lung cancer (NSCLC) patients are still unknown. In the present study, we investigated the associations between single nucleotide polymorphisms (SNPs) of TYMS gene and response to chemotherapy as well as clinical outcomes in NSCLC patients. Five SNPs in TYMS gene were genotyped using the Sequenom iPLEX genotyping system in a hospital-based cohort with 500 NSCLC patients, and their associations with NSCLC outcomes were evaluated by Cox proportional hazard regression analysis under three genetic models (additive, dominant, and recessive models). Our data showed that there was no significant association between individual SNP and overall survival of NSCLC patients. However, SNP rs2847153 was significantly associated with NSCLC recurrence under recessive model. We further identified a significant interaction between rs2847153 and chemotherapy in modifying clinical outcome of patients. Our data showed that individuals carrying GG/GA genotypes of rs2847153 had a significantly better response to chemotherapy when comparing to those carrying AA genotype. Conclusively, our data suggest that SNPs rs2847153 in TYMS gene may be a potential biomarker for predicting clinical outcome and personalized treatment in NSCLC patients.