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Cancer Chemother Pharmacol. 2010 Feb;65(3):437-46. doi: 10.1007/s00280-009-1046-1. Epub 2009 Jul 1.

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

Author information

1
Clinical Medicine College of Southeast University, and Zhongda Hospital, 210009, Nanjing, Jiangsu, China.

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.

PMID:
19568750
PMCID:
PMC2797421
DOI:
10.1007/s00280-009-1046-1
[Indexed for MEDLINE]
Free PMC Article

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