MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer

Abstract

Purpose: The level of drug metabolism and drug transport is correlated with the sensitivity of cancer cells towards platinum-based chemotherapy. We hypothesize that genetic polymorphisms in metabolising enzymes gene GSTP1 (glutathione S-transferase P1), and MRP2 (multidrug resistance-associated protein 2) (ABCC2), which result in inter-individual differences in metabolism and drug disposition, may predict clinical response to platinum agents in advanced non-small cell lung cancer (NSCLC) patients. Methods: Totally 113 patients with advanced NSCLC were routinely treated with platinum-based chemotherapy, and clinical response was evaluated after four cycles. MRP2 C-24T (-24C>T), MRP2 Val417Ile (1249G>A), MRP2 Ile1324Ile (3972C>T), and GSTP1 Ile105Val (342A>G) genotype were determined by gene-chip method (a 3-D (three dimensions) polyacrylamide gel-based DNA microarray method) using DNA samples isolated from peripheral blood collected before treatment. Pearson Chi-square test and Fisher's exact test were performed to measure the differences of the chemotherapeutic efficacy among variant genotype. The odds ratios and 95% confidence intervals were computed by logistic regression. Results: The C→T change of MRP2 C-24T and the A→G change of GSTP1 Ile105Val polymorphism significantly increased platinum-based chemotherapy response. Conclusion: The polymorphic status of MRP2 C-24T and GSTP1 Ile105Val might be the predictive markers for the treatment response of advanced NSCLC patients. The DNA microarray-based method is accurate, high throughput and inexpensive, suitable for single-nucleotide polymorphism genotyping in a large number of individuals.