SNP analysis in ATP binding cassette Solute carrier transporters and Thymidylate synthase genes in North Indian lung cancer patients

Abstract

Background: Lung carcinoma is the second most common type of cancer (accounting for 13% of all occurrences) and the leading cause of carcinoma fatalities. Drug transporters are well-known mediators of drug disposition that facilitate drug influx and efflux from cells. Polymorphisms in transporter genes and drug targets alters intracellular concentrations of drugs that determine the efficacy, toxicity, and clinical outcomes in lung cancer patients. Objective: To evaluate the sequence variants of ABC (ABCB1, ABCC1, ABCC2, and ABCG2) and SLC (SLC19A1, SLCO1B1, and SLCO1B3) drug transporters and Thymidylate synthase gene (chemotherapeutic target) in North Indian population. Methodology: Lung cancer patients undergoing platinum-based chemotherapy were recruited in the current study. Genotyping of ABCB1 (C1236T, C3435T, and G2677T/A), ABCC1 (G3173A and G2168A), ABCC2 (G4544A), ABCG2 (C421A), SLC19A1 (G80A), SLCO1B1 (A388G, T521C), SLCO1B3 (A1683-5676G), TS TSER (2R/3R), and TS 1494del6 polymorphisms were evaluated using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). The univariate Kaplan-Meier method was used to assess overall survival in lung cancer patients. Cox regression analysis was employed to retrieve the adjusted hazard ratio. Stratified analysis was carried out to estimate risk for subgroups based on different clinicopathological parameters, clinical outcome, and toxicity by odds ratios (ORs) and 95% confidence intervals (CIs). In all analyses, a p-value of lt0.05 was chosen to be significant. Results: Poor survival outcomes were noted in patients carrying heterozygous genotype (CT) for ABCB1 C1236T polymorphism as compared to the wild-type genotype (CC) (p=0.04). Patients with ADCC harboring heterozygous (CT) genotype for ABCB1 C1236T had lower survival as compared to the patients having wild type (CC) genotype (p=0.03).