Genetic Polymorphism of Thymidylate Synthase gene in Lung Cancer Patients Undergoing Platinum Based Chemotherapy

Abstract

This study aimed to explain the role of TS (Thymidylate synthase) gene in overall survival of lung cancer patients in North Indian population. TS is involved in folate metabolism. It plays a key role in DNA methylation, synthesis and repair. The SNP used in this study is TSER rs34743033. There are polymorphic tandem repeats in TS gene in TSER (Thymidylate synthase enhancer region). There are variable number of tandem repeats (VNTRs) in TSER namely as two repeats (2R), three repeats (3R) and can be up to nine repeats (9R). In the present study, two common polymorphisms have been studied 2R and 3R. MATERIAL AND METHODS: 150 cases of lung cancer patients were conducted for overall survival of lung cancer patients on the basis of age, gender, smoking status, histology, regimen, pack years, KPS, ECOG and TNM studies. DNA was isolated from peripheral blood and the PCR/RFLP (polymerase chain reaction/restriction fragment length polymorphism) was used to detect the polymorphisms of interest. The amplified product was run on N - PAGE (Native – Polyacrylamide gel electrophoresis) gel. RESULTS: An analysis of gene polymorphism was performed with respect to the overall survival of 150 lung cancer patients treated with platinum based chemotherapy. Patients with heterozygous (2R/3R) genotype had overall survival of 9.47 months with highly significant value of 0.02 which is more than homozygous (2R) genotype. CONCLUSION: TSER rs34743033 genotype appears to be a potential prognostic factor for advanced NSCLC patients treated with platinum based chemotherapy.