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

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 prot...

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Autores principales: Sun, Ning, Sun, Xinchen, Chen, Baoan, Cheng, Hongyan, Feng, Jifeng, Cheng, Lu, Lu, Zuhong
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797421/
https://www.ncbi.nlm.nih.gov/pubmed/19568750
http://dx.doi.org/10.1007/s00280-009-1046-1
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author Sun, Ning
Sun, Xinchen
Chen, Baoan
Cheng, Hongyan
Feng, Jifeng
Cheng, Lu
Lu, Zuhong
author_facet Sun, Ning
Sun, Xinchen
Chen, Baoan
Cheng, Hongyan
Feng, Jifeng
Cheng, Lu
Lu, Zuhong
author_sort Sun, Ning
collection PubMed
description 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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spelling pubmed-27974212009-12-29 MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer Sun, Ning Sun, Xinchen Chen, Baoan Cheng, Hongyan Feng, Jifeng Cheng, Lu Lu, Zuhong Cancer Chemother Pharmacol Original Article 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. Springer-Verlag 2009-07-01 2010 /pmc/articles/PMC2797421/ /pubmed/19568750 http://dx.doi.org/10.1007/s00280-009-1046-1 Text en © The Author(s) 2009 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Article
Sun, Ning
Sun, Xinchen
Chen, Baoan
Cheng, Hongyan
Feng, Jifeng
Cheng, Lu
Lu, Zuhong
MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer
title MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer
title_full MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer
title_fullStr MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer
title_full_unstemmed MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer
title_short MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer
title_sort mrp2 and gstp1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797421/
https://www.ncbi.nlm.nih.gov/pubmed/19568750
http://dx.doi.org/10.1007/s00280-009-1046-1
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