SLC19A1 and Thymidylate Synthase Polymorphisms Do not Predict Survival Outcome in Non-Small-Cell Lung Cancer Treated with Pemetrexed-Cisplatin Chemotherapy Regimen

Abstract

Background: Lung cancer is the leading cause of cancer deaths worldwide. Pharmacogenomics plays an important role in tailoring cancer patients’ treatment. Pemetrexed is widely used in first- and second-line chemotherapy of non-small cell lung cancer (NSCLC); however, there is no available predictive biomarker for pemetrexed treatment. The present study aimed to investigate the role of polymorphisms in thymidylate synthase and SLC19A1 polymorphisms with clinical outcome in patients with advanced NSCLC treated in first-line with pemetrexed or pemetrexed plus cisplatin.Method: This cohort study included 40 metastatic lung cancer patients treated with pemetrexed plus cisplatin. We utilized the tetra-primer amplification refractory mutation system-polymerase chain (ARMS-PCR) reaction for genotyping of rs3788189 and rs1051298. TYMS 28-VNTR and rs16430 were genotyped in the patients via PCR amplification and PCR-RFLP, respectively. Fisher's exact test and Kaplan-Meier curve were used for statistical analysis.Results: We recruited 40 patients in this research with a median age of 58.9 years. The median survival of all the 40 patients was 11.6 months. The overall survival of the patients, as well as their gender, age, and metastatic sites were not found to be statistically associated with rs1051298, rs3788189, TYMS VNTR, and rs16430.Conclusion: Our study did not identify any associations between the SLC19A1 and TYMS VNTR and rs16430 and clinical outcomes in advanced NSCLC patients. However, further investigation will be conducive to finding effective clinical biomarkers for the treatment of patients with NSCLC.

Keywords

• non-small cell lung cancer
• thymidylate synthase
• slc19a
• pemetrexed
• polymorphism