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Respiration. 2008;75(4):380-5. Epub 2007 Sep 12.

MDR1 single nucleotide polymorphisms predict response to vinorelbine-based chemotherapy in patients with non-small cell lung cancer.

Author information

1
Key Laboratory, Ministry of Public Health, Biotech-Drugs, Shandong Medicinal and Biotechnology Center, Shandong Academy of Medical Sciences, Jinan, China. pjh933@yahoo.com.cn

Abstract

BACKGROUND:

The polymorphisms of genes participate in metabolism and transport, and therefore may have an impact on the response to vinorelbine.

OBJECTIVES:

To investigate whether genotypes of CYP3A5, MDR1 and cyclooxygenase-2 (COX-2) are associated with the response to vinorelbine in non-small cell lung cancers (NSCLC).

METHODS:

We determined the genotypes of CYP3A5(*3), MDR1 (2677G-->T at exon 21 and 3435C-->T at exon 26 and their haplotypes) and COX-2 (-1195G-->A) polymorphisms by PCR-RFLP and chemotherapy response in 69 Chinese Han patients with NSCLC who received a combination chemotherapy of vinorelbine-cisplatin (VC). The chi(2) test was used to investigate potential associations between genotypes and response to chemotherapy. Odds ratios and 95% confidence intervals were calculated.

RESULTS:

The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotypes (p = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Moreover, we analyzed the haplotypes of MDR1 3435-2677: patients harboring the 2677G-3435C haplotype had a statistically significantly better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). CYP3A5*3 is not likely to correlate with sensitivity to vinorelbine in NSCLC. COX-2 (-1195G) is likely to result in a better response to vinorelbine (nonsignificant).

CONCLUSIONS:

Our findings suggest that MDR1 2677G-->T/A and 3435C-->T polymorphisms can be used to predict treatment response to VC chemotherapy in NSCLC patients.

PMID:
17851225
DOI:
10.1159/000108407
[Indexed for MEDLINE]

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