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


CONCLUSIONS
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.
Sun
Ning
N
Clinical Medicine College of Southeast University, and Zhongda Hospital, 210009, Nanjing, Jiangsu, China.
Sun
Xinchen
X
Chen
Baoan
B
Cheng
Hongyan
H
Feng
Jifeng
J
Cheng
Lu
L
Lu
Zuhong
Z
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017239:Paclitaxel / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
C000715087:ABCC2 protein, human; C412617:KLHL1 protein, human; D008840:Microfilament Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D016190:Carboplatin; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D017239:Paclitaxel; D002945:Cisplatin