MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer |
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Authors: | Ning Sun Xinchen Sun Baoan Chen Hongyan Cheng Jifeng Feng Lu Cheng Zuhong Lu |
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Affiliation: | 1. Clinical Medicine College of Southeast University, 210009, Nanjing, Jiangsu, China 2. Zhongda Hospital, Southeast University, 210009, Nanjing, Jiangsu, China 3. Jiangsu Cancer Hospital, 210009, Nanjing, Jiangsu, China 4. State Key Laboratory of Bioelectronics, Southeast University, 210096, Nanjing, Jiangsu, China
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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. |
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